Additional Information In Patients Research Articles

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT Study)

Abstract Background Liver dysfunction contributes to worse clinical outcome in heart failure (HF) patients, and cholestatic enzymes are associated with mortality in the setting of chronic HF (CHF). However, the temporal evolutions of liver function parameters in stable CHF patients, and their associations with clinical outcome, have not yet been investigated. Purpose We aimed to investigate in detail the temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB), and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction (HFrEF). Methods During 2.2 (1.4–2.5) years of follow-up, we collected 1984 tri-monthly plasma samples in 263 patients. We selected 749 samples in the 250 HFrEF patients included in the study - all baseline samples, the last two samples before censoring in event-free patients, and the last two samples preceding the primary endpoint (PEP; composite of cardiac death, heart transplantation, LVAD implantation, and hospitalization for the management of acute or worsened HF). In these samples ALP, GGTP, and ALB were measured using colorimetric assays, TBIL using diazomethod, all by Roche/Hitachi Cobas c analyser. The relationship between repeatedly measured biomarker levels and the PEP was evaluated by joint models. Results Mean age was 68±18 years; 74% were men, 25% in NYHA class III or IV. 66 patients (26%) reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP and ALB were associated with the PEP in a model adjusted for NT-proBNP and hs-TnT (hazard ratio (HR) [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p=0.002; 1.84 [1.09; 3.05], p=0.018, 1.33 [1.08; 1.63], p=0.006 and 1.14 [1.09; 1.20], p<0.001, respectively). Serially measured ALP and GGTP remained significantly associated with the PEP after adjustment for clinical covariates (HR [95% CI]: 1.13 [1.07; 1.19], p=0.018; 1.03 [1.01; 1.06], p=0.006, respectively). The levels of ALP and GGTP were higher in patients who experienced the PEP than in event-free patients long before the PEP occurred (>2 years), and as the PEP approached, levels diverged slightly between those with and without the PEP (Figure 1). Conversely, levels of ALB were higher in those with subsequent PEP, >2 years before the PEP, and subsequently fell; while TBIL levels rose less than 1 year before the PEP in those with subsequent PEP. The slopes of the temporal evolution of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP (HR [95% CI] per 20% decrease in the slope for albumin and increase in the slope of TBIL per year: 1.61 [1.43; 1.84], p<0.001 and 1.72 [1.28; 2.55], p<0.001, respectively). Conclusions Changes in serum levels of TBIL, ALP, GGTP and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in HFrEF patients in clinical practice. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Jaap Schouten Foundation (Rotterdam, the Netherlands)Noordwest Academie (Alkmaar, the Netherlands)

H3K27me3 Immunohistochemical Loss Predicts Lower Response to Neo-Adjuvant Chemo-Radiotherapy in Rectal Carcinoma.

A watch-and-wait approach was suggested to avoid the possible complications related to surgery in patients with rectal carcinoma showing clinical complete response after neoadjuvant chemo-radiotherapy (CRT). Since clinical response may not correlate with pathological response, markers with higher accuracy are needed to identify patients who are likely responders and could be spared surgery. This study aims to assess whether H3K27me3 immunohistochemical expression in pre-treatment rectal carcinoma predicts response to neoadjuvant CRT or shows prognostic relevance. We assessed H3K27me3 immunostaining in 46 endoscopic biopsies of rectal carcinomas treated with neoadjuvant CRT and surgery. H3K27me3 immunostaining was lost in 20, retained in 19, and inconclusive (absent in neoplastic and non-neoplastic cells) in 7 cases. Retained H3K27me3 immuno-expression was significantly associated with ypTNM stage 0 (p = 0.0111) and high tumor regression, measured using either five-tiered (p = 0.0042) or two-tiered Dworak tumor regression grade (p = 0.0009). Poor differentiation, determined counting the number of poorly differentiated clusters (PDC grade) or tumor budding (TB) foci (TB grade), in the pre-treatment biopsy, was significantly associated with a shorter time to progression after surgery (p = 0.008; p = 0.0093). However, only PDC grade (p = 0.0023), together with radial margin involvement (p = 0.0001), retained prognostic significance in the multivariate analysis. The assessment of H3K27me3 immunostaining in pre-treatment endoscopic biopsy of rectal carcinoma could be useful to predict response to neo-adjuvant CRT and to identify patients who could safely undergo watch-and-wait approach. PDC and TB grade in the pre-treatment biopsy could provide additional prognostic information in patients with rectal carcinoma treated with neoadjuvant CRT and surgery.

Predictors and prognostic significance of persistent fluid overload: A longitudinal study in Chinese peritoneal dialysis patients.

Cross-sectional studies showed that fluid overload (FO) measured by bioimpedance spectroscopy (BIS) predicted adverse outcomes in patients on peritoneal dialysis (PD). We aimed to describe the longitudinal change in volume status in Chinese PD patients and determine its relation with clinical outcomes. We performed a single-centre, retrospective analysis of all PD patients who underwent repeated BIS from 2010 to 2015. FO was defined by relative hydration index (RHI; volume of overhydration adjusted by extracellular water >7%). Variability of volume status (VVS) was denoted by the standard deviation of all RHI. The association of time-averaged RHI and VVS on patient and technique survival was explored by a competing risk model. A total of 269 patients were followed for a median of 47.1 months. Mean time-averaged RHI was 17.6 ± 10.2%. Multivariable mixed linear regression revealed that RHI was significantly associated with diabetes, time-varying systolic blood pressure, and inversely with time-varying albumin level, lean tissue index and fat tissue index (p <0.0001 for all). Time-averaged RHI independently predicted patient survival (subdistribution hazard ratio (SHR) 1.05, 95% CI 1.03-1.07, p <0.0001) and technique survival (SHR 1.04, 95% CI 1.02-1.06, p <0.0001), whereas VVS did not. The mortality risk for patients with persistent FO was consistently higher than the corresponding risk estimated from baseline FO of the same extent. Persistent FO was a strong predictor of patient and technique failure. Repeated bioimpedance measurements to monitor volume status may provide additional prognostic information in PD patients.

When does CT myelography add value beyond MRI for lumbar degenerative disease?

Background ContextIn patients with lumbar spinal stenosis, it is crucial for clinicians to identify all symptomatic levels. Prior studies have demonstrated that CT myelography has a greater sensitivity in revealing stenosis (94.4%) compared to MRI (75.9%). However, this is an invasive test that should be used judiciously. No study has identified subgroups of patients that do or do not benefit from this additional invasive testing. PurposeThe objective of this study was to identify subgroups of patients with lumbar stenosis for whom CT myelogram could be expected to provide additional information following an MRI scan. Study DesignRetrospective chart review. Patient SampleConsecutive series of patients with lumbar degenerative disease seen at a single multisurgeon tertiary spine center. Outcome measuresDegree of stenosis on MRI or CT myelo. MethodsMedical records were reviewed to collect standard demographic and surgical data and patient diagnoses. MRI and CT myelo obtained within 6 months of each other in patients >45 years old with a diagnosis of central stenosis, spondylolisthesis or degenerative scoliosis were reviewed. Each lumbar level was recorded as mild, moderate, or severe based on the radiologist's report. Fisher exact test was performed with change in recorded severity of stenosis from MRI to CT myelo as the primary outcome of interest. ResultsOf 269 patients, 207 (80%) had at least one level of moderate or severe central stenosis on MRI and 62 had mild or no stenosis on MRI. Of the 207, 139 (67%) had multilevel stenosis and 68 (33%) had single level stenosis. CT myelo identified a greater proportion of additional stenotic levels in patients with multilevel stenosis (80/139, 58%) compared to patients with single-level stenosis (27/68, 40%, p=.018). In 62 patients with a clinical diagnosis of lumbar stenosis but no moderate to severe stenosis on MRI, CT myelogram identified three additional stenotic levels (3/65, 5%, p=.836). ConclusionSCT myelography is not as useful in providing additional information in patients with no stenosis or single level stenosis as compared to patients with multilevel stenosis.

Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19

Rationale & ObjectiveAcute kidney injury (AKI) is common in patients with coronavirus disease 2019 (COVID-19) and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. We investigated the association between urinary biomarkers and adverse kidney outcomes among patients hospitalized with COVID-19.Study DesignProspective cohort study.Setting & ParticipantsPatients hospitalized with COVID-19 (n = 153) at 2 academic medical centers between April and June 2020.Exposure19 urinary biomarkers of injury, inflammation, and repair.OutcomeComposite of KDIGO (Kidney Disease: Improving Global Outcomes) stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings.Analytical ApproachTime-varying Cox proportional hazards regression to associate biomarker level with composite outcome.ResultsOut of 153 patients, 24 (15.7%) experienced the primary outcome. Twofold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR, 1.34 [95% CI, 1.14-1.57]), monocyte chemoattractant protein (MCP-1) (HR, 1.42 [95% CI, 1.09-1.84]), and kidney injury molecule 1 (KIM-1) (HR, 2.03 [95% CI, 1.38-2.99]) were associated with highest risk of sustaining primary composite outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR, 0.61 [95% CI, 0.47-0.79]). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. The degree of kidney injury by biomarker level in COVID-19 was comparable to other settings of clinical AKI. There was evidence of subclinical AKI in COVID-19 patients based on elevated injury biomarker level in patients without clinical AKI defined by serum creatinine.LimitationsSmall sample size with low number of composite outcome events.ConclusionsUrinary biomarkers are associated with adverse kidney outcomes in patients hospitalized with COVID-19 and may provide valuable information to monitor kidney disease progression and recovery.

Adverse Histopathologic Characteristics in Small Papillary Renal Cell Carcinomas Have Minimal Impact on Prognosis.

Tumor size has long been used in the management decision-making of patients with renal masses. Active surveillance had recently gained traction in selected patients with tumor size of 4 cm or less. Adverse histopathologic characteristics in papillary renal cell carcinoma (PRCC) have been shown to correlate with worse prognosis. We aimed to study whether such features in small PRCCs provide additional prognostic information. Nephrectomies from our institution were collected and reviewed to evaluate for adverse histopathologic features. Clinical follow-up information was collected for all cases. Relationships between the variables were examined by Wilcoxon test and logistic regression. We identified 291 consecutive cases of PRCC. Adverse tumor histopathologic characteristics were significantly related to size. In PRCCs with size greater than 4 cm, there were more cases with high World Health Organization/International Society of Urological Pathology grade and necrosis. Adverse histologic features are less commonly seen in small PRCC and are not associated with lower disease-free survival or disease-specific survival. Identification of these features in small PRCCs (≤4 cm) through needle core biopsy examination would not provide additional prognostic information in patients for whom active surveillance is considered. Clinical and radiologic follow-up in patients with small renal masses that have a known histologic diagnosis of PRCC should be sufficient.

144. Recognizing patients in whom CT-myelography detects additional level of stenosis compared to MRI

<h3>BACKGROUND CONTEXT</h3> In patients with lumbar spinal stenosis, it is crucial for clinicians to identify all symptomatic levels. Prior studies have demonstrated that CT-myelography has a greater sensitivity in revealing stenosis (94.4%) compared to MRI (75.9%). CT-myelograms demonstrate weight-bearing changes as opposed to single position and single time point changes on MRI. However, CT-myelography is invasive, requiring injection of contrast dye into the thecal sac. <h3>PURPOSE</h3> The purpose of this study is to identify patients in whom additional levels of stenosis are likely to be recognized by a CT-myelogram following an MRI scan. <h3>STUDY DESIGN/SETTING</h3> Retrospective observational cohort at a single multi-surgeon spine center. <h3>PATIENT SAMPLE</h3> Patients ≥45 years old who had an MRI followed by a CT-myelogram within 6 months with a diagnosis of stenosis, spondylolisthesis, or degenerative scoliosis. <h3>OUTCOME MEASURES</h3> Additional levels of moderate to severe stenosis identified on CT-myelogram vs MRI. <h3>METHODS</h3> Medical records were reviewed to collect standard demographic and surgical data and to note if patients were deemed to have single-level or multi-level stenosis clinically. MRIs and CT-Myelograms obtained within six months of each other were reviewed and each lumbar level was recorded as mild, moderate, or severe based on the radiologist's report. Fisher's exact test was performed with change in recorded level of stenosis from MRI to CT-Myelogram as the primary outcome of interest. <h3>Results</h3> Of 207 patients, 139 (67%) had clinically reported multilevel stenosis and 68 (33%) had single-level stenosis. CT-Myelogram identified a greater proportion of additional stenotic levels in patients with clinically reported multilevel stenosis (80/139, 58%) compared to patients with single-level stenosis (27/68, 40%, p=0.018). When classifying patients based on MRI findings of stenosis instead of clinical diagnosis, 90 (43%) patients had multi-level stenosis, and 117 (56%) had single-level stenosis. In patients with radiologist-reported multilevel stenosis, CT-myelogram also identified a greater proportion of additional stenotic levels (55/90, 61%) compared to patients with radiologist-reported single level stenosis (52/117, 44%, p=0.025). <h3>Conclusions</h3> CT myelography is significantly more likely to provide valuable additional information in patients with multilevel stenosis as compared to patients with single level stenosis. This finding was consistent regardless of whether the distinction of single-level or multilevel stenosis was determined by clinical diagnosis or based solely off the MRI report. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Prognostic Value of Liver Stiffness Measured by Two-Dimensional Elastography in Acute Decompensated Heart Failure with Preserved Ejection Fraction.

Liver stiffness (LS) assessed by ultrasound elastography reflects right-sided filling pressure and offers additional prognostic information in patients with acute decompensated heart failure (ADHF). However, the prognostic value of LS in heart failure (HF) with preserved ejection fraction (HFpEF) remains unclear. This study aimed to investigate the prognostic value of LS measured by two-dimensional shear wave elastography (2D-SWE) in patients with HFpEF.We prospectively enrolled 80 patients hospitalized for decompensated HFpEF between September 2019 and June 2020. Patients were categorized into three groups based on the tertile values of LS at discharge.The third tertile LS group had an older age; more advanced New York Heart Association functional class; higher total bilirubin, γ-glutamyl transferase (GGT), N-terminal pro-B type natriuretic peptide (NT pro-BNP), and Fibrosis-4 index; a larger right ventricle diastolic diameter, higher tricuspid regurgitation pressure gradient, and a larger maximal inferior vena cava diameter. During a median [interquartile range] follow-up period of 212 (82-275) days, 25 (31.2%) patients suffered composite end points (all-cause mortality and rehospitalization for worsening HF). The third tertile LS group had a significantly higher rate of composite end points (log-rank P = 0.002). A higher LS and the third tertile LS were significantly associated with the composite end points, even after adjusting for a conventional validated HF risk score and other previously reported prognostic risk factors.Increased LS measured by 2D-SWE reflects the severity of liver impairment by liver congestion and fibrosis, underlying right HF, and provides additional information for the prediction of poor outcomes in HFpEF.

Analysis of correlations between driver mutations and biomarkers with response to immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC).

e21022 Background: Next-generation sequencing (NGS) performs genomic profiling on tumor tissue and provides information on mutations on 300+ selected genes. While driver mutations have targeted therapy options, apt therapies for passenger mutations are not clearly defined. The level of PD-L1 expression and the total mutation burden (TMB) score for NSCLC have independent predictive values in response to check-point inhibition immunotherapy. Using NGS data, we aimed to evaluate the correlations of driver mutations and other biomarkers with immunotherapy response. Methods: We performed a retrospective analysis on the NGS results for NSCLC patients treated between November 2011 and February 2018. Patients were identified from the Foundation Medicine Company database and were linked to records at our cancer center. Patients’ demographics and treatment data were assessed. Results: 99 NSCLC patients (44 males and 55 females) were included with a median age of 65 (range 32-89). Races included Asian (n=42), Caucasian (n= 40), African American (n=8), and Hispanic (n=7). 49 patients possessed driver mutations, which were EGFR (n=22), ALK (n=5), RET (n=5), ROS (n=2), BRAF (n=5), MET amplification (n=5), BRCA 1 or 2 (n=4), and NTRK (n=2); 3 patients had both a driver and a non-driver mutation. In the entire cohort, 40 patients (58 total, 69%) had PD-L1 tumor proportion score (TPS) &gt; 0% and 31 (53%) had TPS ≥10%. 30 patients (48 total, 63%) had TMB &lt;10 and 18 (37%) had TMB ≥10. Patients with driver mutations had a lower probability of high TMB (p=0.007), but no difference in PD-L1 expression (p=0.61). PD-L1 TPS score had no correlation with TMB high or low scores (Table). In patients with driver mutations, other mutations were detected by NGS. In EGFR+ patients, the most common additional mutations were TP53 and CDKN2A/B. 23 patients received immunotherapy; the response rate in non-mutation carriers was 45.4% (5/11). Among the 7 patients with an EGFR mutation, 4 had PD-L1 TPS ≥30% and none had TMB ≥10; based on RECIST 1.1, stable disease (SD) was the best response in 2 patients. One patient with a BRAF mutation and another patient with an ALK mutation had partial responses (PR); both had TMB ≥ 10. Conclusions: NGS provides additional information in NSCLC patients with driver mutations. In patients with driver mutations, while PD-L1 expression may not be associated with response to immunotherapy, a high TMB level may be a predictive biomarker, which warrants further study.[Table: see text]

The value of ecocardiographic in diagnostication and management of pacients with acute pulmonary embolism

Pulmonary thromboembolism (TP) remains an underdiagnosed fatal disease at the emergency unit that suggests the need for alternative noninvasive approaches to rapid diagnosis. The role of echocardiography in acute pulmonary embolism (EP) remains incompletely defined. Echocardiography cannot reliably diagnose acute EP and does not improve the prognosis of patients with low-risk acute PE, who lack other clinical characteristics of right ventricle dysfunction (VD). However, echocardiography and dopplerography of the venous system may produce additional information in high-risk patients and may help differentiate chronic VD dysfunction. Specific echocardiographic predictors of VD dysfunction have the potential to increase prognosis in patients at high risk of TP.

2D speckle tracking echocardiography as predictor of major adverse cardiac events (MACE) in patients with non ST elevation myocardial infarction and unstable angina

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND 2D speckle strain echocardiography has been recognized in different studies to provide additional important prognostic information in patients with chronic stable coronary artery disease or acute coronary syndrome (ACS)—more often on (ST elevation myocardial infarction (STEMI) patients. PURPOSE This study aimed to determine the clinical utility of 2D speckle tracking echocardiography in predicting major adverse cardiac events (MACE) in patients with non ST elevation – acute coronary syndrome (NSTE-ACS). METHODOLOGY This is a prospective cohort study which included 91 patients diagnosed to have NSTE-ACS. Baseline characteristics were collected and echocardiographic evaluations of patients were done within 48 hours of admission. In hospital and 6 months MACE were evaluated in relation to their baseline echocardiographic parameters, 2D speckle strain and strain rate analyses. RESULTS Among the conventional echocardiographic parameters, only left ventricular end systolic diameter (LVESD) and wall motion score showed significant difference between those with and without outcomes after 6 months. There were no significant difference among the 2D speckle tracking strain and strain rate parameters between those patients with and without major cardiac events during their in hospital admission. However after 6 months follow-up, there were significantly lower mean left ventricular global longitudinal strain (GLS) (-14.22% ± 4.45 versus -16.44% ± 4.19, p-value 0.0261) and strain rate (-0.69 1/sec ± 0.36 versus -0.94 1/sec ± 0.25, p-value 0.009) were observed among patients with MACE compared to those without. Also, incidence of reduced GLS strain and strain rate, were significantly higher in those with MACE after 6 months. The left ventricular global circumferential strain and strain rate, and right ventricular global longitudinal strain did not have significant difference between those with and without but these had a generally lower value among those who had in-hospital and 6 months MACE. In this study, LV GLS sensitivity and specificity were 64.64% and 61.70% respectively, at cut-off value of &amp;lt;-15.0% for detecting MACE within 6 month follow-up. LV GLS cut-off point &amp;lt;-12.0%, which detects severe LV dysfunction in previous studies, have sensitivity of 40% but high specificity of 82.98% for predicting MACE after 6 months. CONCLUSION Both LV GLS strain and strain rate can be used to predict major adverse cardiovascular events after NSTE-ACS. Abstract Figure. ROC curve LV strain and strain rate

Elevated echocardiographic markers for left atrial stiffness and fibrosis in patients with paroxysmal atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Danderyds Hospital Background Atrial fibrillation (AF) is associated with atrial disease expressing left atrial (LA) structural remodeling with increased fibrosis and stiffness. Transthoracic echocardiography (TTE) is the first imaging modality of choice for the evaluation of LA volume index (LAVI) and function. However TTE allows new approaches for LA anatomical and functional analysis such as LA stiffness index (LASI) calculation based on LA global longitudinal strain (GLS), LA activation time and LA Integrated Backscatter (IBS). LA activation time is a novel parameter, considered as an echocardiographic surrogate analysis for LA fibrosis. Echocardiographic derived IBS can noninvasively quantify myocardial fibrosis in the left ventricle, allowing a similar alternative analysis for LA fibrosis. Purpose To investigate potential LA structural and functional changes in paroxysmal AF patients by measuring LA activation time, LASI and LA IBS compared with age-matched control group. Methods In total, 75 paroxysmal AF patients and 99 age-matched control group patients (mean age 77 ± 0.4) were enrolled from STROKESTOP2 study. Patients with paroxysmal AF were included from a subgroup of newly screened-diagnosed AF. TTE examinations were analyzed retrospectively offline using dedicated software. NTproBNP levels ( ≤ 900 ng/L) was an enrollment criterium. LA activation time was acquired by measuring the time delay between the onset of the P-wave on ECG and the peak of the Á –wave on the Tissue Doppler (TD) tracing in the lateral LA wall. LASI was calculated as the ratio of E/é to LA-GLS. LA IBS was obtained as the intensity difference between the LA lateral wall and the pericardium, at QRS peak. Results There was a significant increase of LASI (0.53 ± 0.21 vs. 0.41 ± 0.22, P &amp;lt; 0.05) and LA IBS (14 ± 7.1 dB vs. 11 ± 6.3 dB, P &amp;lt; 0.05) in the AF group compared to the control group. Feasibility for LASI resulted as 64 %, respectively 91 % for LA IBS. LA activation time was significantly prolonged in the AF group (157 ± 34 ms vs. 134 ± 18 ms, P &amp;lt; 0.05) with a feasibility of 44 %. In the AF group, 45 patients (60 %) expressed normal LAVI &amp;lt;34 ml/m2. No significant difference was revealed concerning LAVI (P &amp;gt; 0.05) between the groups (AF group with normal LAVI). Although LASI, LA IBS and LA activation time remained significant increased in the AF group (P &amp;lt; 0.05). No significant difference was shown regarding NT-proBNP levels. (P &amp;gt; 0.05) between the AF group 243 (179-420) ng/L and the control group 219 (160-317) ng/L. Conclusions Indices reflecting LA stiffness and echocardiographic parameters associated with LA fibrosis, were elevated in patients with paroxysmal AF compared to age-matched controls. These findigs might non-invasively provide additional information in paroxysmal AF patients with normal LA size.

Genomic variations in patients with myelodysplastic syndrome and karyotypes without numerical or structural changes

Myelodysplastic syndrome (MDS) is an onco-hematologic disease with distinct levels of peripheral blood cytopenias, dysplasias in cell differentiation and various forms of chromosomal and cytogenomic alterations. In this study, the Chromosomal Microarray Analysis (CMA) was performed in patients with primary MDS without numerical and/or structural chromosomal alterations in karyotypes. A total of 17 patients was evaluated by GTG banding and eight patients showed no numerical and/or structural alterations. Then, the CMA was carried out and identified gains and losses CNVs and long continuous stretches of homozygosity (LCSHs). They were mapped on chromosomes 1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 14, 16, 17, 18, 19, 20, 21, X, and Y. Ninety-one genes that have already been implicated in molecular pathways important for cell viability were selected and in-silico expression analyses demonstrated 28 genes differentially expressed in mesenchymal stromal cells of patients. Alterations in these genes may be related to the inactivation of suppressor genes or the activation of oncogenes contributing to the evolution and malignization of MDS. CMA provided additional information in patients without visible changes in the karyotype and our findings could contribute with additional information to improve the prognostic and personalized stratification for patients.

THE ROLE OF ULTRASOUND ELASTOGRAPHY IN THE DIAGNOSIS OF PATHOLOGIC CONDITIONS OF TESTICLES AND SCROTUM.

SUMMARYSeveral years ago, elastography emerged as a potentially very useful ultrasound technique that is currently used in diagnostic workup of the breast, liver and some other organ systems, whereas for other ones it is still mainly in the phase of research. The aim of the study was to compare elasticity index (EI) of testicles using strain elastography in healthy subjects and those with pathologic changes of testicles/scrotum. A total of 117 patients were included in the study. Measurements were performed on a Logiq E9 ultrasound system using strain elastography. In healthy subjects, the mean EI value was 1.34±0.35 for right testis and 1.49±0.47 for left testis. Increased mean EI values were found in the following six conditions: patients with varicocele, infertile patients, solitary testis after orchidectomy of the other testicle because of tumor, patients with testicular tumors, patients after orchidopexy of undescended testicle, and patients with congenitally smaller testicle. There is a paucity of literature data on the use of elastography in testes, as well as on normal elastography values in testicular tissue. Strain elastography was demonstrated to be a valuable method to acquire additional information in patients with pathologic changes in testicles/scrotum. These data provide reference values for further research in a larger sample of subjects.

Evaluation of the aortic velocity propagation, epicardial fat thickness, and carotid intima-media thickness in patients with subclinical hypothyroidism.

Subclinical hypothyroidism (SH) is associated with hemodynamic and metabolic abnormalities that cause endothelial dysfunction and atherosclerotic cardiovascular diseases. Aortic velocity propagation (AVP), epicardial fat thickness (EFT), and carotid intima-media thickness (CIMT) may provide additional information in SH patients. This study aimed to evaluate thyroid stimulating hormone (TSH), AVP, EFT, and CIMT in SH patients, and determine the associations among these parameters. Eighty patients with SH and 43 euthyroid (EU) individuals were enrolled. Blood samples were collected to measure laboratory parameters. Patients were divided into two groups based on their TSH values (TSH ≥10 or TSH <10 mIU/L). AVP, EFT, and CIMT were measured and compared between the study groups. A multivariate linear regression model was used for analysis of the independent predictors of AVP (beta = -0.298; 95% confidence interval = -0.946 to -0.287; p < 0.001). AVP was significantly lower in SH patients than the control group (43.7 ± 12.5 and 62.6 ± 13.8, respectively; p < 0.001). EFT values were similar between the SH and control groups (0.7 ± 0.3 and 0.6 ± 0.2, respectively; p = 0.10). SH patients had higher CIMT values than the control group (0.8 ± 0.3 and 0.5 ± 0.2, respectively; p < 0.001). In the multivariate linear analysis, TSH was an independent predictor of AVP. AVP was lower and CIMT was higher in SH patients compared to EU individuals. The increased CIMT and decreased AVP levels were significantly associated with TSH levels in SH patients.

Absolute Monocyte and Platelet Counts May Provide Additional Prognostic Information in Primary Gastric Diffuse Large B-cell Lymphoma Patients Treated with Rituximab and CHOP.

Primary gastric diffuse large B cell lymphoma (PG-DLBCL) is the most common histological subtype of primary gastric lymphoma. The standard of care of PG-DLBCL patients is the combination rituximab-based immunochemotherapy (R-CHOP). Re-cently, different host-related factors have been shown to have significant prognostic significance in non-Hodgkin lymphoma. However, data regarding their prognostic contribution to PG-DLBCL are limited. To assess the prognostic impact of a panel of simple, cost-effective laboratory variables which are easy to apply in routine labora-tory use for R-CHOP-treated PG-DLBCL patients in an attempt to identify those among them that are high-risk category. We retrospectively assessed the possible prognostic impact of different laboratory markers in 42 R-CHOP treated PG-DLBCL patients treated between 2004 and 2014 and followed at a single institution. The estimated 5-year overall (OS) and progression-free survival (PFS) of the whole group were 80.9% and 78%, respectively. The absolute monocyte and platelet counts in univariate analysis predicted PFS and OS when analyzed as continuous and dichotomized variables. On multivariate analysis performed with factors included in the stage-modified International Prognostic Index (m-IPI), the absolute monocyte and platelet counts remained independent predictors of PFS and OS. Therefore, the absolute monocyte and platelet counts were combined to generate a prognostic index that identified patients with an especially poor overall survival. This prognostic index was independent of the m-IPI and could provide additional prognostic information for better stratification of these patients.

Prognostic value of global longitudinal strain versus mitral annular plane systolic excursion in patients with ischemic heart failure

Abstract Background Mitral annular plane systolic excursion (MAPSE) derived from M-mode echocardiography is a classical risk factor of clinical outcome in heart failure patients. Two-dimensional-echocardiography (2DE) derived global longitudinal strain (GLS) is also related to outcome in patients with heart failure. This study aimed to compare the prognostic performance between GLS and MAPSE in ischemic heart failure patients with reduced ejection fraction. We sought to test the hypothesis that GLS might be superior to MAPSE as a risk stratification marker in these patients. Methods In total, 1277 ischemic heart failure patients with reduced left ventricular ejection fraction (LVEF&amp;lt;50%), referred to our department between 2009 and 2017, were included in this retrospective study. Offline standard echocardiographic measurements including MAPSE and GLS were performed. Average MAPSE of septal and lateral walls (MAPSE_Avg) was calculated. GLS was derived from the segmental averaging (18-segment) of the three apical views. All patients completed at least one-year clinical follow-up by telephone interview or clinical visit. The primary endpoint was defined as all-cause mortality or heart transplantation (HTx). Results At baseline visit, mean age was 70±11 years and 79.6% were men. NYHA class III-IV were identified in 33.5% of patients. Coronary artery disease was confirmed by coronary angiography. 63.0% patients had a history of myocardial infarction, 32.1% underwent PCI, and 16.8% underwent coronary artery bypass grafting. Over a median follow-up period of 26 (14–39) months, 369 (28.9%) patients died and 5 (0.4%) underwent HTx. Median LVEF was 39% (32–45%), and there were 48.0% patients with LVEF between 40–49%, 32.3% patients with LVEF between 30–49% and 19.7% patients with LVEF &amp;lt;30%. MAPSE_Avg was 8.0 (6.5–10.0) mm and median GLS was −9.9% (−7.7 to −12.3%). Clinical covariates significantly associated with all-cause mortality in this cohort included age (HR=1.048), NYHA class III-IV (HR=1.800), AF (HR=1.567), diabetes (HR=1.262), dyslipidemia (HR=0.657), hyperuricemia (HR=1.861), peripheral vascular disease (HR 1.858), chronic respiratory diseases (HR=1.680), and renal dysfunction (HR=2.705). Multivariable Cox regression analysis showed that reduced MAPSE_Avg (&amp;lt;7mm, HR=1.431, 95% CI 1.146–1.786) and reduced GLS (&amp;lt;8.3%, HR=1.519, 95% CI 1.230–1.875) were independent predictors of all-cause mortality after adjustment of above-mentioned clinical confounders. ROC curves demonstrated that the predictive performance of all-cause mortality among LVEF, MAPSE_Avg, and GLS were similar (AUC=0.608, 0.601, and 0.616, respectively, all P&amp;lt;0.001). Conclusions Both 2DE-guided GLS and MAPSE could provide additional prognostic information in ischemic heart failure patients with reduced LVEF. Prognostic performance of GLS, MAPSE, and LVEF is similar in ischemic heart failure patients with reduced LVEF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The German Federal Ministry of Education and Research

Dividing Stage 1 Acute Kidney Injury After Cardiac or Thoracic Aortic Surgery

Although the Kidney Disease: Improving Global Outcomes (KDIGO) criteria are used to define acute kidney injury, the criteria have limitations for including 2 different serum creatinine criteria in stage 1. We hypothesized that there would be differences in clinical outcomes between the 2 subgroups of stage 1 acute kidney injury in patients undergoing cardiac or thoracic aortic surgery. We reviewed 2510 cases. Patients with KDIGO stage 1 were divided into 2 subgroups (stage 1a: 0.3 mg/dL or greater of absolute increase in serum creatinine, n= 376; and stage 1b: 50% or greater relative increase, n= 365). Propensity score analysis was performed between stage 1a and 1b groups, yielding 240 pairs. We compared the length of hospital stay, the incidence of cardiovascular complications, 5-year all-cause mortality between these subgroups. Overall survival was compared between the subgroups after propensity score matching. We performed sensitivity analysis for Acute Kidney Injury Network (AKIN) criteria. Length of hospital stay and 5-year all-cause mortality were worse in patients with KDIGO stage 1b compared with stage 1a. Five-year patient survival was significantly worse in patients with stage 1b compared with stage 1a after matching (log rank test, P= .002). We found similar results regarding AKIN criteria. Subgroup analysis showed that the significant difference in survival existed only when baseline serum creatinine was 0.8 mg/dL or greater. The KDIGO or AKIN criteria for stage 1 acute kidney injury could be further divided into 2 substages with different severity of clinical outcomes. These modified criteria could give additional prognostic information in patients undergoing cardiac or thoracic aortic surgery.

Comparison of a combination test (1 μg ACTH test plus glucagon test) versus 1 μg ACTH test and glucagon test in the evaluation of the hypothalamic-pituitary-adrenal axis in patients with pituitary disorders.

To investigate whether a combination of the low-dose (1 μg) adrenocorticotropin (ACTH) stimulation test and glucagon stimulation test (GST) could overcome the problem of equivocal results with the GST or ACTH test alone in patients with pituitary disorders. The study included 41 adult patients with pituitary disorders and 20 healthy subjects who underwent evaluation of cortisol response to ACTH, GST, and a combination of both tests. Blood samples for cortisol measurement were obtained at baseline and 30, 60, 90, and 120 minutes after intravenous administration of ACTH 1 μg and 90, 120, 150, 180, 210, and 240 minutes after subcutaneous injection of glucagon 1 mg. The combination test was performed by injecting ACTH 1 μg at the 180-minute time point of the GST, with blood samples for cortisol measurement obtained at 210 and 240 minutes. Overall, 28 patients with normal cortisol response to both tests also had a normal cortisol response to the combination test. Ten patients with adrenal insufficiency in both tests also had adrenal insufficiency in the combination test, including a patient who had a peak cortisol value of 12.4 μg/dL (which is the cutoff value for the combination test). Two patients with adrenal insufficiency in the ACTH stimulation test and one patient with adrenal insufficiency in the GST had normal cortisol responses to the combination test. By using an appropriate cutoff value, the combination test may offer additional information in patients with equivocal results in the GST and ACTH stimulation test.

Pretreatment 18F-FDG PET/CT texture parameters provide complementary information to Epstein-Barr virus DNA titers in patients with metastatic nasopharyngeal carcinoma.

The aim of the present study was to evaluate whether texture features extracted from 18F-FDG PET/CT images may provide additional prognostic information in patients with metastatic nasopharyngeal carcinoma (NPC). We retrospectively examined 52 patients with metastatic NPC who underwent assessment of EBV DNA titers and pretreatment 18F-FDG PET/CT imaging. All participants were followed up for at least two years. The following 18F-FDG PET parameters were analyzed: standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and texture parameters. Independent predictors of outcomes were identified using receiver operating characteristic curve analysis and multivariate Cox proportional hazards models. On multivariate analysis, EBV DNA titers>3500 copies/mL and TLG of metastatic lesions>138mL were identified as independent predictors of overall survival (OS) (P=0.036 and P=0.047, respectively). Patients were divided into two subgroups based on their EBV DNA titers (high versus low). In the high EBV DNA titer group, a lower homogeneity of distant metastatic lesions and higher TLG values of distant metastatic lesions were independent risk factors for OS (P=0.033 and P<0.001, respectively). In the low EBV DNA titer group, a reduced uniformity of distant metastatic lesions and a higher SUVmax of distant metastatic lesions were unfavorable risk factors for OS (P=0.004 and P=0.005, respectively). Based on these results, we devised two prognostic scoring systems for the prediction of 2-year OS in each EBV DNA titer group. Some of the PET-derived texture parameters are independent predictors of outcomes in patients with metastatic NPC and provide complementary information to EBV DNA titers.