Impact Of Clinical Parameters Research Articles

The Impact of Clinical Parameters on LSTM-based Blood Glucose Estimate in Type 1 Diabetes

Accurate forecasting of blood sugar levels is essential for managing diabetes, especially Type-1 reducing incidences, and diminishing care, costs in patients. In this study, a Long Short-Term Memory Recurrent Neural Network (LSTM) model has been employed to predict blood glucose levels using clinical data. The research focuses on identifying and analyzing several key parameters that play a significant role in determining future blood glucose levels, ensuring a robust and reliable prediction framework. We have considered patient-specific features: Insulin-Sensitivity-Factor (ISF), total daily dose (TDD) of insulin, HbA1C levels, height and weight of a patient, and age and gender while analyzing the prediction performance for Blood Glucose. We thought training LSTM models on a large dataset and studying the most important predictors with their predictive power would be beneficial. The results indicate that including these clinical parameters improves the accuracy of blood glucose prediction and provides valuable information for individuals to control diabetes. This analysis highlights the efficiency of LSTM networks in making use of patient data to improve prediction models, eventually aiding more effective and individualized treatment strategies for Type 1 diabetic patients (T1D). This work also examines the extent to which each parameter influences the prediction of future blood glucose levels, providing deeper insights into their relative impact and significance in the predictive model.

The CALR mutations enhance the expression of the immunosuppressive proteins GARP and LAP on peripheral blood lymphocytes through increased binding of activated platelets.

Recently, an antibody which inhibits the glycoprotein A repetitions predominant (GARP)-mediated release of active transforming growth factor beta (TGFβ) from the TGFβ propeptide latency-associated peptide (LAP) showed preclinical activity in a murine model of the chronic myeloproliferative neoplasms (MPN). Consequently, we investigated the expression of the immunosuppressive molecules LAP and GARP on peripheral blood lymphocytes from 56 MPN patients and 11 healthy donors (HD). We found that lymphocytes from patients with MPN express higher levels of LAP and GARP with no strong differences found between the different MPN diagnoses. The impact of clinical parameters on the expression of LAP and GARP by lymphocytes showed that patients with calreticulin (CALR)mut MPN have increased expression compared with HD and patients with the Januskinase2 (JAK2) mutation. The fraction of lymphocytes bound to activated platelets (aPLT) strongly correlate to LAP and GARP expression suggesting that it is not the lymphocytes themselves but aPLT, which confer the increased expression of GARP and LAP on MPN patient lymphocytes. Notably, no differences in neither platelet counts nor anti-thrombotic therapy was identified between patients with JAK2- and CALRmut patients. Analysis of platelet gene expression failed to identify differences in expression of relevant genes between JAK2- and CALRmut patients.

Impact of Clinical Parameters and Induction Regimens on Peripheral Blood Stem-Cell Mobilization and Collection in Multiple Myeloma Patients

Introduction: High-dose chemotherapy (HDCT) followed by autologous blood stem-cell transplantation (ABSCT) remains the standard consolidation therapy for newly diagnosed eligible multiple myeloma (MM) patients. As a prerequisite, peripheral blood stem cells (PBSCs) must be mobilized and collected by leukapheresis (LP). Many factors can hamper PBSC mobilization/collection. Here, we provide a comprehensive multiparametric assessment of PBSC mobilization/collection outcome parameters in a large cohort. Methods: In total, 790 MM patients (471 [60%] male, 319 [40%] female) who underwent PBSC mobilization/collection during first-line treatment were included. Evaluated PBSC mobilization/collection outcome parameters included the prolongation of PBSC mobilization, plerixafor administration, number of LP sessions, and overall PBSC collection goal/result. Results: 741 (94%) patients received cyclophosphamide/adriamycin/dexamethasone (CAD) and granulocyte-colony-stimulating factor (G-CSF) mobilization. Plerixafor was administered in 80 (10%) patients. 489 (62%) patients started LP without delay. 530 (67%) patients reached the PBSC collection goal at the first LP session. The mean overall PBSC collection result was 10.3 (standard deviation [SD] 4.4) × 106 CD34+ cells/kg. In a multiparametric analysis, variables negatively associated with PBSC mobilization/collection outcomes were female gender, age >60 years, an advanced ISS stage, and local radiation pre-/during induction, but not remission status postinduction. Notably, the identified risk factors contributed differently to each PBSC mobilization/collection outcome parameter. In this context, compared to all other induction regimens, lenalidomide-based induction with/without antibodies negatively affected only the number of LP sessions required to reach the collection goal, but no other PBSC mobilization/collection outcome parameters. In contrast, the probability of reaching a high collection goal of ≥6 × 106 CD34+ cells/kg body weight was higher after lenalidomide-based induction compared to VCD/PAD or VAD – taking into account – that a higher G-SCF dosage was given in approximately one-third of patients receiving lenalidomide-based induction with/without antibodies. Conclusion: Considering the identified risk factors in the clinical setting can contribute to optimized PBSC mobilization/collection. Moreover, our study demonstrates the necessity for a differentiated evaluation of PBSC mobilization/collection outcome parameters.

Predicting Long-term Survival After Lung Metastasectomy in Patients With Malignant Germ-cell Tumors.

The aim of the study was to identify predictors of long-term survival and propose an improved risk stratification in patients with pulmonary germ-cell metastases admitted for pulmonary metastasectomy. Thirty-four patients admitted to the Division of Thoracic Surgery Munich, Germany, from 04/1994 until 09/2017 were retrospectively analyzed. The impact of clinical parameters on survival was calculated using Kaplan-Meier, multivariate Cox regression analysis and receiver-operator curves. Ten-year overall survival was 75.3%. Elevated American Society of Anesthesiologists score, metachronous metastasis, embryonal histology, intrathoracic lymph node involvement, brain metastases and thoracic wall infiltration were significant predictors of reduced survival. With the independent predictors (embryonal histology, metachronous metastasis and thoracic wall infiltration), a germinal non-seminomatous lung metastasis risk of death score (GLUMER) was calculated, accurately predicting survival (area under curve=0.8839, p=0.0023). In patients with pulmonary germ-cell metastases, intrathoracic lymph node involvement, embryonal carcinoma, metachronous metastasis and thoracic wall infiltration represent negative predictors of long-term survival. The GLUMER score might represent a promising tool for use in adapted follow-up care in high-risk patients.

Predictive value of clinical and 18F-FDG-PET/CT derived imaging parameters in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma

Aim of this study was to validate the prognostic impact of clinical parameters and baseline 18F-FDG-PET/CT derived textural features to predict histopathologic response and survival in patients with esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiation (nCRT) and surgery. Between 2005 and 2014, 38 ESCC were treated with nCRT and surgery. For all patients, the 18F-FDG-PET-derived parameters metabolic tumor volume (MTV), SUVmax, contrast and busyness were calculated for the primary tumor using a SUV-threshold of 3. The parameter uniformity was calculated using contrast-enhanced computed tomography. Based on histopathological response to nCRT, patients were classified as good responders (< 10% residual tumor) (R) or non-responders (≥ 10% residual tumor) (NR). Regression analyses were used to analyse the association of clinical parameters and imaging parameters with treatment response and overall survival (OS). Good response to nCRT was seen in 27 patients (71.1%) and non-response was seen in 11 patients (28.9%). Grading was the only parameter predicting response to nCRT (Odds Ratio (OR) = 0.188, 95% CI: 0.040–0.883; p = 0.034). No association with histopathologic treatment response was seen for any of the evaluated imaging parameters including SUVmax, MTV, busyness, contrast and uniformity. Using multivariate Cox-regression analysis, the heterogeneity parameters busyness (Hazard Ratio (HR) = 1.424, 95% CI: 1.044–1.943; p = 0.026) and contrast (HR = 6.678, 95% CI: 1.969–22.643;p = 0.002) were independently associated with OS, while no independent association with OS was seen for SUVmax and MTV. In patients with ESCC undergoing nCRT and surgery, baseline 18F-FDG-PET/CT derived parameters could not predict histopathologic response to nCRT. However, the PET/CT derived features busyness and contrast were independently associated with OS and should be further investigated.

Prediction of neo-adjuvant chemotherapy response in bladder cancer: the impact of clinical parameters and routine biomarkers

Purpose To investigate the role of clinical parameters and immunohistochemical (IHC) biomarkers in their feasibility to predict the effect of neo-adjuvant chemotherapy (NAC) in patients with muscle-invasive urothelial bladder cancer (MIBC). Materials and methods The first 76 consecutive patients with MIBC treated with NAC and radical cystectomy in two University hospitals in Finland between 2008 and 2013 were chosen for this study. After excluding patients with non-urothelial cancer, less than two cycles of chemotherapy, no tissue material for IHC analysis or non-muscle-invasive bladder cancer in re-review, 59 patients were included in the final analysis. A tissue microarray block was constructed from the transurethral resection samples and IHC stainings of Ki-67, p53, Her-2 and EGFR were made. The correlations between histological features in transurethral resection samples and immune-histochemical stainings were calculated. The associations of clinicopathological parameters and IHC stainings with NAC response were evaluated. Factors affecting survival were estimated. Results The complete response rate after NAC was 44%. A higher number of chemotherapy cycles was associated with better response to neo-adjuvant chemotherapy. No response to neo-adjuvant chemotherapy and female gender was associated with decreased cancer-specific survival. The IHC stainings used failed to show an association with neo-adjuvant chemotherapy response and overall or cancer specific survival. Conclusions Patients who do not respond to neo-adjuvant chemotherapy do significantly worse than responders. This study could not find clinical tools to distinguish responders from non-responders. Further studies preferably with larger cohorts addressing this issue are warranted to improve the selection of patients for neo-adjuvant chemotherapy.

Impact of clinical parameters and vascular haemodynamics on arterio-venous fistula maturation in patients with end stage renal disease: A prospective study on Indian patients.

About 18%-65% of Arterio-Venous fistula (AVF) made to facilitate haemodialysis in end stage renal disease patient fail to mature. This study was designed to evaluate the impact of clinical parameters and vascular haemodynamics on maturation of AVF on Indian patients. This was a prospective observational study. Eligible patients' clinical profiles and vascular haemodynamics by Doppler ultrasonography were noted. All patients underwent radio-cephalic AVF on the non-dominant arm under local anaesthesia. Clinical definition was used to assess success rate of AVFs which is defined as successful six settings of satisfactory dialysis. Data were analysed using Stata/12.0 software. Independent t-test, chi-square test, logistic regression analysis and multivariate analysis were used. The p-value of <0.05 was considered significant. A total of 205 patients were enrolled and analysed. Among clinical factors, age, sex, serum creatinine, hypertension had no significant association with failure (p = 0.5, 0.08, 0.76 and 0.74). Patient's BMI and presence of diabetes had significant impact on outcome (p < 0.001 and 0.02 respectively). Among vascular haemodynamics, radial vein diameter of >2.5 mm and radial artery flow rate >40 ml/min had no significant association with failure (p = 0.12 and 0.28). Diameter of radial artery (>2 mm) and intra-operatively immediate thrill were independent predictor of success (p = 0.002 and <0.001). In the present study rate of fistula, maturation was 73.2% without any post-operative radiological intervention. Radial artery diameter >2 mm and presence of immediate thrill post-operatively were significantly associated with successful cannulation.

Transarterial drug delivery for liver cancer: numerical simulations and experimental validation of particle distribution in patient-specific livers

ABSTRACT Background: Transarterial therapies are routinely used for the locoregional treatment of unresectable hepatocellular carcinoma (HCC). However, the impact of clinical parameters (i.e. injection location, particle size, particle density etc.) and patient-specific conditions (i.e. hepatic geometry, cancer burden) on the intrahepatic particle distribution (PD) after transarterial injection of embolizing microparticles is still unclear. Computational fluid dynamics (CFD) may help to better understand this impact. Methods: Using CFD, both the blood flow and microparticle mass transport were modeled throughout the 3D-reconstructed arterial vasculature of a patient-specific healthy and cirrhotic liver. An experimental feasibility study was performed to simulate the PD in a 3D-printed phantom of the cirrhotic arterial network. Results: Axial and in-plane injection locations were shown to be effective parameters to steer particles toward tumor tissue in both geometries. Increasing particle size or density made it more difficult for particles to exit the domain. As cancer burden increased, the catheter tip location mattered less. The in vitro study and numerical results confirmed that PD largely mimics flow distribution, but that significant differences are still possible. Conclusions: Our findings highlight that optimal parameter choice can lead to selective targeting of tumor tissue, but that targeting potential highly depends on patient-specific conditions.

Predictors of the start of declining eGFR in patients with systemic lupus erythematosus.

To characterize the longitudinal trajectory of estimated glomerular filtration rate (eGFR) in patients with systemic lupus erythematosus (SLE) and identify predictors of the change in eGFR trajectory. The longitudinal eGFR levels of patients in the Hopkins Lupus Cohort were modelled by piecewise linear regression to evaluate the slope of different line segments. The slopes were classified into declining (≤-4 mL/min/1.73 m2 per year), stable (-4 to 4 mL/min/1.73 m2 per year), and increasing (≥4 mL/min/1.73 m2 per year) states. The transition rate between states and the impact of clinical parameters were estimated by a Markov model. The analysis was based on 494 SLE patients. At a mean follow-up of 8.8 years, 347 (70.2%), 107 (21.7%), 33 (6.7%), and 7 (1.4%) patients had zero, one, two, and three state transitions, respectively. In patients with no transition, 37 (10.7%), 308 (88.8%), and 2 (0.6%) were in declining, stable, and increasing state, respectively. In patients with one transition, 43 (40.2%) changed from declining to stable state while 29 (27.1%) changed from stable to declining state. When patients were in a non-declining GFR state, those who were younger and African Americans were more likely to transition to a declining GFR state. In adjusted analyses, high blood pressure, C4 and low hematocrit were associated with change from non-declining to declining state. High urine protein-to-creatinine ratio also tended to be associated with change from non-declining to declining state. African American patients were less likely to move from declining to non-declining state. Use of prednisone was associated with change from declining to non-declining state. Patients with high blood pressure, low complement C4, low haematocrit, and high urine protein-to-creatinine ratio are more likely to have a declining eGFR trajectory, while the use of prednisone stabilizes the declining eGFR trajectory.

The altered gut microbiota in adults with cystic fibrosis

BackgroundCystic Fibrosis (CF) is an autosomal recessive disease that affects the function of a number of organs, principally the lungs, but also the gastrointestinal tract. The manifestations of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the gastrointestinal tract, as well as frequent antibiotic exposure, undoubtedly disrupts the gut microbiota. To analyse the effects of CF and its management on the microbiome, we compared the gut microbiota of 43 individuals with CF during a period of stability, to that of 69 non-CF controls using 454-pyrosequencing of the 16S rRNA gene. The impact of clinical parameters, including antibiotic therapy, on the results was also assessed.ResultsThe CF-associated microbiome had reduced microbial diversity, an increase in Firmicutes and a reduction in Bacteroidetes compared to the non-CF controls. While the greatest number of differences in taxonomic abundances of the intestinal microbiota was observed between individuals with CF and the healthy controls, gut microbiota differences were also reported between people with CF when grouped by clinical parameters including % predicted FEV1 (measure of lung dysfunction) and the number of intravenous (IV) antibiotic courses in the previous 12 months. Notably, CF individuals presenting with severe lung dysfunction (% predicted FEV1 ≤ 40%) had significantly (p < 0.05) reduced gut microbiota diversity relative to those presenting with mild or moderate dysfunction. A significant negative correlation (−0.383, Simpson’s Diversity Index) was also observed between the number of IV antibiotic courses and gut microbiota diversity.ConclusionsThis is one of the largest single-centre studies on gut microbiota in stable adults with CF and demonstrates the significantly altered gut microbiota, including reduced microbial diversity seen in CF patients compared to healthy controls. The data show the impact that CF and it's management have on gut microbiota, presenting the opportunity to develop CF specific probiotics to minimise microbiota alterations.

The relationship between clinical parameters and lifestyle variables among patients with severity of coronary artery stenosis: A cross-sectional analysis based on the severity of coronary artery stenosis.

INTRODUCTION:Cardiovascular diseases are the leading cause of death all over the world. Lifestyle can have an important role not only in reducing risk factors but also in the prevention and treatment of coronary heart diseases. The aim of this study was to examine the relationship between clinical parameters and various aspects of patients’ lifestyles according to the severity of their coronary artery stenosis.MATERIALS AND METHODS:This study was a descriptive, analytic study carried out on 220 patients undergoing coronary angiography at Mazandaran Heart Center. Based on the angiography results, patients were divided into two groups: artery stenosis > 50% (110 cases) and < 50% (110). Patients’ lifestyles were evaluated using health-promoting behavior questionnaire. Blood pressure and triglyceride, low-density lipoprotein, high-density lipoprotein, cholesterol, and fasting blood sugar were also measured. After collecting data, SPSS 21 software, Chi-square test, t-test, and multiple linear regression were used for analysis of the data.RESULTS:The results showed that in patients with positive angiographic data, there is a significant correlation between clinical parameters and dimensions of health-promoting behavior (P < 0.05).CONCLUSION:Given the impact of clinical parameters on various aspects of lifestyle, it seems that by teaching the different aspects of lifestyle (such as having a healthy diet consisting of fresh fruits and vegetables, reducing intake of saturated fat, physical activity and regular exercise, stress management, and blood pressure control) to patients with a positive angiographic result, we can improve their lifestyles by means of improving clinical parameters.

Impact of clinical parameters and systemic inflammatory status on epidermal growth factor receptor-mutant non-small cell lung cancer patients readministration with epidermal growth factor receptor tyrosine kinase inhibitors.

BackgroundEpidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration to lung cancer patients is common owing to the few options available. Impact of clinical factors on prognosis of EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKI readministration after first-line EGFR-TKI failure and a period of TKI holiday remains unclear. Through this retrospective study, we aimed to understand the impact of clinical factors in such patients.MethodsOf 1386 cases diagnosed between December 2010 and December 2013, 80 EGFR-mutant NSCLC patients who were readministered TKIs after failure of first-line TKIs and intercalated with at least one cycle of cytotoxic agent were included. We evaluated clinical factors that may influence prognosis of TKI readministration as well as systemic inflammatory status in terms of neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR).Baseline NLR and LMR were estimated at the beginning of TKI readministration and trends of NLR and LMR were change amount from patients receiving first-Line TKIs to TKIs readministration.ResultsMedian survival time since TKI readministration was 7.0 months. In the univariable analysis, progression free survival (PFS) of first-line TKIs, baseline NLR and LMR, and trend of LMR were prognostic factors in patients receiving TKIs readministration. In the multivariate analysis, only PFS of first-line TKIs (p < 0.001), baseline NLR (p = 0.037), and trend of LMR (p = 0.004) were prognostic factors.ConclusionLonger PFS of first-line TKIs, low baseline NLR, and high trend of LMR were good prognostic factors in EGFR-mutant NSCLC patients receiving TKI readministration.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2917-6) contains supplementary material, which is available to authorized users.

The impact of clinical parameters on progression-free survival of non-small cell lung cancer patients harboring EGFR-mutations receiving first-line EGFR-tyrosine kinase inhibitors

ObjectivesIn daily practice, some patients with certain clinical characteristics may have better responses to the administration of epidermal growth factor receptor (EGFR)—tyrosine kinase inhibitors (TKIs). It is therefore reasonable to stratify and weigh the importance of these clinical parameters which may not only affect patients’ responses to TKIs but also progression-free survival (PFS) other than the impact of EGFR mutation status per se. Materials and methodsThis retrospective study evaluated EGFR-mutant, non-small cell lung cancer patients who received EGFR-TKIs as a first-line therapy between January 2011 and December 2013. Several potential prognostic factors were analyzed with respect to PFS, and the results of this analysis were validated in another time cohort. ResultsA total of 262 patients were included in the study. Age≤40 years, uncommon EGFR mutations, poor performance status, more sites of distal metastasis, and blood lymphocyte to monocyte ratio≤3 were independently associated with poor PFS. These five factors were included in a scoring system and three prognostic groups A, B, and C, were formed based on total scores of 0–1, 2, and ≥3, respectively.In the test group, the PFS was 15.7 month, 9.3 month, and 4.0 month in groups A, B, and C, respectively (p<0.001). Between the test and validation groups, no significant differences were found in each one of the three prognostic groups. ConclusionsThe scoring system appears valid and reproducible for PFS prognosis in EGFR-mutant patients who received first-line EGFR-TKIs.

Mutations in Histone Modulators Are Associated with Prolonged Survival during Azacitidine Therapy

Early therapeutic decision-making is crucial in patients with higher-risk MDS where median survival is only around one year. Azacitidine prolongs survival for these patients (Fenaux et al, Lancet Oncology 2009) but clinically relevant biomarkers remain to be identified. We evaluated retrospectively, the impact of clinical parameters and mutational profiles in 134 consecutive patients treated with a median number of 7 cycles of Azacitidine (range 1-45), in accordance to European guidelines. The vast majority (n=114) had higher-risk disease i.e. MDS with IPSS int-2 or high, AML with multilinear dysplasia and 20-30% blasts or CMML-II. We combined an initial cohort from Karolinska University Hospital (n=89) with a validating cohort from King's College Hospital, London (n=45). Studied endpoints were response, as defined by the IWG criteria, and survival. Since prolonged survival is the main goal for this cohort of patients, we believe that survival is the most relevant endpoint, supported by the fact that even non-responding patients have a survival benefit from Azacitidine (Gore et al, Haematologica, 2013).While neither clinical parameters nor mutations had a significant impact on response rate, both karyotype and mutational profile were strongly associated with survival from the start of treatment, see Table 1 and Figure 1-2. IPSS high-risk cytogenetics was negatively associated with survival (median 20 vs 10 months; p<0.001), whereas mutations in histone modulators (ASXL1, EZH2, MLL) were associated with prolonged survival (22 vs 12 months, p=0.001). This positive association was present in both cohorts and remained highly significant in the multivariate cox model. Importantly, patients with mutations in histone modulators lacking high-risk cytogenetics showed a survival of 29 months (response rate 73%) compared to 10 months (response rate 49%) in patients with the opposite pattern, see Figure 3. While TP53 was negatively associated with survival in the univariate analysis, neither RUNX1-mutations nor the number of mutations, previously reported as negative prognostic markers, appeared to influence survival in this cohort. In contrast, disease duration and cellularity showed a weak negative correlation with survival. We propose a model combining histone modulator mutational screening with cytogenetics in the clinical decision-making process for higher-risk MDS eligible for treatment with Azacitidine.Table 1Variables associated with survival. Univariate analyses used the log-rank test. The cox model included all listed variables except response rate in a multivariate analyses.Estimated median survival (months)Univariate p-valueCox regression p-valueHazard ratio (95% CI)Response rate: CR / mCR vs PR/HI vs SD/PD20 vs 20 vs 10<0.001IPSS cytogenetic risk group: Favorable vs Int vs Adverse20 vs 20 vs 10<0.001<0.001*3.00 (1.9-4.7)Disease duration ≥ 4 months: Yes vs No14 vs 170.440.05**1.01 (1.00-1.02)Marrow blasts ≥ 11%: Yes vs No14 vs 140.7Cellularity ≥ 70%: Yes vs No14 vs 200.20.021.013 (1.002-1.023)**ANC ≥ 1.3: Yes vs No14 vs 170.32Platelets ≥ 60: Yes vs No17 vs 120.07Transfusion dependent: Yes vs No13 vs 170.43Therapy related: Yes vs No17 vs 140.44Number of mutations: 0 vs 1 vs ≥ 217 vs 12 vs 170.64Epigenetic mutation: Yes vs No19 vs 120.03DNA methylation mutation: Yes vs No14 vs 140.64Histone modulator mutation: Yes vs No22 vs 120.0010.0070.499 (0.3-0.83)Splicing factor mutation: Yes vs No13 vs 170.31ASXL1 mutation: Yes vs No29 vs 120.03TET2 mutation: Yes vs No13 vs 160.45EZH2 mutation: Yes vs No20 vs 140.37SF3B1 mutation: Yes vs No13 vs 160.35RUNX1 mutation: Yes vs No17 vs 140.76SRSF2 mutation: Yes vs No20 vs 140.5TP53 mutation: Yes vs No9 vs 17<0.001*Comparing adverse cytogenetics vs the other groups. ** Disease duration, marrow blasts, cellularity, ANC and TPK were analyzed as a continuous variable in the cox model [Display omitted] [Display omitted] [Display omitted] DisclosuresMcLornan:Novartis: Research Funding, Speakers Bureau. Jädersten:Celgene: Other: speakers fee. Kulasekararaj:Alexion: Consultancy. Mufti:Celgene: Consultancy, Other: Speakers fee. Hellström-Lindberg:Celgene Corporation: Research Funding.

Impact of clinical parameters on surgical outcomes in patients with hematological disorders undergoing splenectomy.

e17689 Background: Safety of splenectomy is of concern in hematological disorders (HD) due to compromised blood indices and platelet dysfunction. Methods: We conducted a retrospective review of cli...

Medication Compliance in Patients with Chronic Pain

Background: Despite hints about the high incidence of pain patients misreporting their pain medication use, there are only a few non-controlled studies on the topic that focus solely on opioids. Objective: Using toxicological analyses in a cross-sectional study, we investigated patients’ reliability regarding their report of any current pain medication use. Study Design: A cross-sectional study. Setting: A comprehensive pain center and a surgical unit of a German University Hospital. Methods: Consecutive outpatients at their first visit to the pain clinic (PG, n = 243) and pre-surgical control patients (SG, n = 100) suffering from pain reported on their current pain medication. The patients’ reports were verified in serum and urine using specific toxicological methods. Two types of noncompliance were defined: under-reporting (detection of non-reported substances) and overreporting (reported substances undetectable). The impact of clinical parameters on compliance was investigated using binary logistic regression. Results: The incidence of noncompliance was significantly higher in the PG (43.3%) than in the SG (24%; P &lt; 0.05). Under-reporting occurred similarly in both groups (31% PG; 23% SG), whereas over-reporting predominantly appeared in the PG (11% vs. 2%; P &lt; 0.05). Opioids were not most frequently under-reported, but the highest proportion of under-reported drugs (underreported in relation to detection incidence) was found for non-opioid analgesics (NSAIDs: 29% PG; 25% SG; other: 42% PG; 32% SG) and psychotropic drugs (35% PG; 53% SG). In the PG, logistic regression revealed high depression scores to be predictive for noncompliance (odds ratio 2.12). Limitations: Due to lack of a structured follow-up interview motives of under- and over-reporting stay speculative. Conclusions: Under-reporting of non-opioid analgesics is the main type of noncompliance, a disquieting fact in light of their toxicity and adverse effects. Further research is required in terms of drug assessment and compliance improvement strategies in pain clinics; therefore, toxicological monitoring is indispensable. Clinical Trial: NCT01625065; Medi-3889-10 Key words: Medication compliance, adherence, chronic pain, toxicological analyses, urine drug testing, NSAID, opioids

Prediction of pathological and oncological outcomes based on extended prostate biopsy results in patients with prostate cancer receiving radical prostatectomy: a single institution study

BackgroundThe prediction of pathological outcomes prior to surgery remains a challenging problem for the appropriate surgical indication of prostate cancer. This study was performed to identify preoperative values predictive of pathological and oncological outcomes based on standardized extended prostate biopsies with core histological results diagrammed/mapped in patients receiving radical prostatectomy for prostate cancer clinically diagnosed as localized or locally advanced disease.MethodsIn 124 patients with clinically localized or locally advanced prostate cancer (cT1c–cT3a) without prior treatment, pathological outcomes on the surgical specimen including seminal vesicle involvement (SVI), positive surgical margin (PSM), and perineural invasion (PNI) were studied in comparison with clinical parameters based on the results of 14-core prostate biopsies comprising sextant, laterally-directed sextant, and bilateral transition zone (TZ) sampling.ResultsConcerning the association of pathological outcomes with oncological outcomes, patients with PSM and PNI on surgical specimens had poorer biochemical-progression-free survival than those without PSM (logrank p = 0.002) and PNI (p = 0.003); it was also poorer concerning SVI, although the difference was not significant (p = 0.120). Concerning the impact of clinical parameters on these pathological outcomes, positive TZ and multiple positive biopsy cores in the prostatic middle were independent values predictive of SVI with multivariate analyses (p = 0.020 and p = 0.025, respectively); both positive TZ and multiple positive prostatic middle biopsies were associated with larger tumor volume (p < 0.001 in both). The percentage of positive biopsy cores (%positive cores) and biopsy Gleason score were independent values predictive of PSM (p = 0.001) and PNI (p = 0.001), respectively. Multiple positive cores in the prostatic base were associated with proximal/bladder-side PSM (p < 0.001), and also linked to poorer biochemical-progression-free survival (p = 0.004). Clinical T stage had no association with these pathological outcomes.Conclusions%positive cores and Gleason score in extended biopsies were independent values predictive of PSM and PNI in prostate cancer clinically diagnosed as localized or locally advanced disease, respectively, which were associated with poorer oncological outcomes. When diagramming biopsy-core results, extended biopsy may provide additional information for predicting oncological and pathological outcomes including SVI in patients clinically diagnosed as having localized or locally advanced disease.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8790262771042628

Abstract 273: Phenotypic Differences Between Human Subcutaneous and Perivascular Adipose Tissues

Objective: Human adipose lies in specific anatomic depots. Peri-vascular adipose appears unique and impacts blood vessel biology, but direct human data is limited. In view of their theorized roles, we tested the hypothesis that human peri-vascular and subcutaneous adipose tissue hold distinct phenotypic signatures. We also evaluated the impact of clinical parameters on adipose phenotype. Methods: Fresh human peri-vascular and subcutaneous adipose tissues were collected intra-operatively from patients undergoing major lower extremity amputation (n=27) and assayed for protein levels of the adipose-associated mediators IL-6, IL-8, leptin, TNF-α, MCP-1, adiponectin, resistin and PAI-1. Results: Leptin (2.4 fold, p=0.045) and adiponectin (1.8 fold, p=0.007) were significantly more abundant in subcutaneous compared to peri-vascular adipose (Table I). Clinical data were used to model associations between clinical characteristics and mediator levels. Age positively correlated with peri-vascular PAI-1 expression (β=0.64, p=0.042), and hyperlipidemia negatively correlated with peri-vascular adipose adiponectin (β=-1.18, p=0.039). Conclusions: While significant similarity was observed between subcutaneous and peri-vascular adipose from leg amputation patients, the differential in adipose derived hormones leptin and adiponectin provides direct human evidence that these tissue compartments hold distinct biologic roles. Further investigation into the unique nature of peri-vascular adipose may provide meaningful guidance in managing peripheral vascular disease.

Impact of Clinical Parameters on the Diagnostic Accuracy of Endorectal Coil MRI for the Detection of Prostate Cancer

Objectives: Endorectal coil MRI (endoMRI) of the prostate is useful to evaluate tumor localization. There is little evidence on patient characteristics affecting its diagnostic performance. We evaluate the influence of clinical and histological parameters on the accuracy of endoMRI. Methods: Sixty-nine patients with prostate cancer were included. After virtually dividing the prostate into pixels of 1 cm², results of endoMRI were compared with those from prostatectomy specimens’ whole-mount sections. Univariate and multivariate analyses were performed to calculate the impact of clinical and histological parameters on the number of appropriately described pixels. Results: In 9, no tumor could be demonstrated by endoMRI. 48.3% of patients were staged correctly, 23.3% were over- and 28.3% understaged. Mean rates of correctly labeled pixels were 0.44 (± 0.04 SEM) for tumor and 0.90 (± 0.01) for benign segments. In univariate analysis, the rate of correctly labeled tumor segments showed significant positive correlations with Gleason score ≧7 and negative correlations with prostate weight and multifocality. The rate of correctly labeled benign segments showed significant negative correlation with tumor weight. All factors were independent variables in multivariate analysis. Conclusions: The reliability of endoMRI depends on clinical parameters. Higher Gleason scores, unifocal tumors and smaller prostate volumes ameliorate endoMRI performance.

Abstract 3126: Pulmonary Valve Replacement In Chronic Pulmonary Regurgitation In Adults With Congenital Heart Disease: Influence Of Preoperative QRS-duration On Postoperative Right Ventricular Function

Background: Chronic pulmonary regurgitation (PR) causes progressive right ventricular (RV) dysfunction and heart failure. Parameters defining the optimal time point for surgery of chronic PR are lacking. The present study prospectively evaluated the impact of clinical parameters, cardiorespiratory function and neurohumoral activation on post operative RV function and volumes assessed with magnetic resonance imaging (MRI) after pulmonary valve replacement in patients with severe PR. Methods and Results: MRI was performed preoperatively and at follow-up 5.2±3.5months after surgery in 27 patients (23.6±2.9 years, 15 women) with severe PR. Underlying cardiac disease was repaired Tetralogy of Fallot (n=22), Double outlet right ventricle (n=3) and PR after pulmonary valvulotomy (n=2). Postoperatively, RV endsystolic (RVESVI) and enddiastolic volume indices (RVEDVI) decreased significantly (RVESVI pre 78,2±20,4 ml/m 2 BSA vs. RVESVI post 52,2±16,8 ml/m 2 BSA, p&lt;0,001; RVEDVI pre 150,7±27,7 ml/m 2 BSA vs. RVEDVI post 105,7±26,7 ml/m 2 BSA; p&lt;0,001). Mean RV ejection fraction (RVEF) remained unchanged in the study cohort (47.6 ± 8.7% vs. 49.7 ±7.0%, n.s.). Preoperative volumes did not correlate with postoperative ejection fraction. With increasing preoperative QRS-duration, postoperative RVEF decreased significantly (r=−0.57; p&lt;0,005). A preoperative QRS-duration smaller than the median (156ms) predicted an improved RVEF as compared to a QRS-duration ≤ 156ms (54.9% vs. 46.8%, p&lt;0.05). Neither elevated NT-proBNP levels nor reduced cardiorespiratory function were able to predict postoperative RVEF. Conclusion: Valve replacement in severe pulmonary regurgitation causes significant reduction of RV volumes. Prolonged preoperative QRS-duration was associated with a worse outcome with respect to postoperative RVEF. During follow-up an increase in QRS-duration in patients with chronic PR might indicate deterioration in RV function reflecting a risk of impaired RV function postoperatively.