scholarly journals Real World Validation of VTE Risk Models in Newly Diagnosed Multiple Myeloma in a Community Setting

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2971-2971
Author(s):  
Shivani Kapur ◽  
Kayla Feehan ◽  
Samuel Mosiman ◽  
Susan Frankki ◽  
Lori J Rosenstein
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Group ◽  
Community Setting ◽  
Low Risk ◽  
Intermediate Risk ◽  
Start Date ◽  
Kaplan Meier ◽  
Therapeutic Anticoagulation

Abstract Background: Multiple Myeloma (MM) is associated with increased risk for venous thromboembolism (VTE). Treatment, such as dexamethasone, immunomodulatory drugs (IMID), alkylating agents, and doxorubicin, alter hemostatic pathways and thus promote thrombogenesis 1. MM patients with VTE have a 3-fold increase in mortality compared to those without VTE, so identifying those at risk and aiming to prevent VTE events is important 2. Several clinical VTE risk prediction scores have been developed, including the SAVED score, IMPEDE VTE score, and more recently the PRISM score 2,4,5. The National Comprehensive Cancer Network suggests that patient with MM on IMID therapy should be on aspirin, or therapeutic anticoagulation for those at "high risk"3. However, it remains unclear which risk model, if any, should be used.Our objective was to validate the three published risk assessment tools in a community setting and assess the predictive ability of each. Methods: We conducted a retrospective chart review of all patients with newly diagnosed multiple myeloma who started chemotherapy at Gundersen Health System (La Crosse, WI) between 2010 and 2020 who had at least 6 months of follow up documented. Patients with prior indication for ongoing therapeutic anticoagulation or a diagnosis of VTE within 6 months prior to starting therapy were excluded. Total scores for IMPEDE VTE, SAVED and PRISM scores were calculated from the chemotherapy start date. Statistical analysis included Chi-square, Fisher's exact and Wilcoxon rank sum tests, and Kaplan Meier survival analysis. A p-value ≤ 0.05 was considered significant and all analysis was completed in SAS version 9.4. Results: Our cohort contained 123 patients diagnosed with MM. Average age was 68 years (SD 12.1, range 37-92). Our study included 68 (55%) males and 55 (45%) females with 121 (98%) being White/Caucasian. The mean BMI of patients was 29.4 kg/m2 (SD 7.0, range 18.6-54.4). Kaplan Meier survival analysis showed a 5-year survival rate of 53.1% (95% CI [42.7%, 63.4%]). In the entire cohort, 10 (8.1%) patients were diagnosed with VTE (as compared to 5.8% in IMPEDE study, 8.7% in SAVED study and 8.2% in PRISM study) with 80.0% occurring within 6 months of treatment start date. Aspirin was the most frequently used agent for thromboprophylaxis with 88 (86.3%) patients receiving either 81, 162, or 325 mg of aspirin. IMID therapy was given to 76 (61.8%) patients, 114 (92.7%) received dexamethasone and 114 (92.7%) received proteasome inhibitors. Amongst those on IMIDs, 72 (94.7%) patients received prophylaxis, most commonly aspirin. Abnormal metaphase cytogenetics were noted in 104 (85.4%) patients. Neither the IMPEDE VTE (p=0.6), SAVED (p=0.9) nor PRISM risk scores (p=0.3) were able to statistically predict VTE outcome in our patient population. Using the IMPEDE score, 7 patients in the intermediate risk group and 3 patients in the low-risk group had a VTE. In the SAVED model, 5 patients in the low-risk group and 5 patients in the high-risk group had a VTE. Using the PRISM risk score, all 10 of the patients with VTE were in the intermediate risk group. Most patients who were on IMID therapy fell into the intermediate risk group on the IMPEDE VTE and PRISM scoring systems, and the SAVED score had an approximately equal patient distribution between the high risk and low risk group. Conclusions: Our patients with multiple myeloma had similar rates of VTE as compared to the published models, with the majority occurring in the first 6 months of chemotherapy. In total, our patients on IMID therapy received appropriate prophylaxis with aspirin. Overall, 8.1% of our patients had a VTE event. However, none of the three risk models were able to predict the development of VTE. In fact, many of the VTE events occurred in patients who were felt to be low or intermediate risk. While the sample size is small and from a single health system, we had excellent follow up and ability to closely examine each chart for treatment and outcomes. Further efforts should focus on collaboration across institutions to increase the sample size, to validate and compare existing models. The majority of myeloma treatment occurs in the community; thus, it is important to ensure the findings are reproducible in that patient population. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identification of Previously Unrecognized Multiple Myeloma Risk Subgroups with a Novel Biological Disease Stratifier

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4718-4718
Author(s):  
Afsaneh M. Shariatpanahi ◽  
Sarah Grasedieck ◽  
Matthew C. Jarvis ◽  
Faezeh Borzooee ◽  
Reuben S. Harris ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Disease Biology ◽  
Kaplan Meier ◽  
Risk Patients ◽  
Patient Subgroups

Abstract Background: The prognosis of MM is determined by affected organs, tumor burden as measured by e.g., the international staging system (ISS), disease biology such as cytogenetic abnormalities, and response to therapy. The outcome of high-risk MM patients classified by ISS or adverse risk cytogenetics is not uniform and patients show heterogeneous survival. Recent insights into the pathogenesis of MM highlighted genome/transcriptome editing as well as inflammation as drivers for the onset and progression of MM. We hypothesized that inclusion of molecular features into risk stratification could potentially resolve the challenge of accurately distinguishing between high-risk and low-risk MM patients at initial diagnosis and improve outcome. Aim: We aimed to create a simple molecular risk score to identify unrecognized patient subgroups, who have been previously misclassified by current risk stratifiers. Method: The Multiple Myeloma Research Foundation CoMMpass study genomics dataset, combining mRNA Seq and clinical data from more than 700 MM patients, allowed us to evaluate the prognostic value of demographic and clinical parameters, cytogenetics, and gene expression levels of APOBEC genes as well as inflammation-modulating cytokines in MM patients. We calculated hazard ratios and Kaplan-Meier survival estimates for all extracted features. Combining clinical variables that were significantly associated with PFS and OS, we then applied machine learning approaches to identify the most accurate classification model to define a new risk score that is easy to compute and able to stratify NDMM patients more accurately than cytogenetics-based classifiers. Based on a Kaplan-Meier survival curve analysis, we then evaluated the performance of our newly built EI score in sub-classifying of current multiple myeloma risk stratifiers. Results: Based on machine learning models, we defined a weighted OS/PFS risk score (Editor-Inflammation (EI) score) based on mRNA expression of APOBEC2, APOBEC3B, IL11, TGFB1, TGFB3, as well as ß2-microglobulin and LDH serum levels. We showed that the EI score subclassified patients into high-risk, intermediate-risk, and low-risk prognostic groups and demonstrated superior performance (C-index: 0.76) compared to ISS (C-index: 0.66) and R-ISS (C-index: 0.64). We further showed that EI low-risk patients do not benefit from autograft and maintenance therapy. Re-classification of ISS (Figure 1a, b, c) and R-ISS risk groups further confirmed the superiority of the EI score. In addition, the EI score identified previously unrecognized distinct subgroups of MM patients with adverse risk cytogenetics but good prognosis (Figure 1d, e, f). For example, the EI score excellently subclassified del(17p) MM patients into three main risk subgroups including a super low-risk group (none of them has p53 mut) with 5-year OS of 100%, an intermediate-risk group (30% of these patients also have p53 mut) with 5-year OS rate of 75%, and a very poor prognosis group of patients (40% of these patients also have p53 mut) with 5-year OS rate of 0% (2y OS: 40%) (Figure 1f). In line, we could show that patients with del(17p) and high EI score exhibit an enrichment of APOBEC induced genomic mutations compared to intermediate-risk and low-risk patients supporting the hypothesis that del(17p) along with high APOBEC expression levels activate the APOBEC mutation program and thus create an optimal environment for tumor progression. These findings support the necessity of a prognostic score that more accurately reflects MM disease biology. Conclusion: Although MM is considered as an incurable disease, an improved risk stratification could help to identify previously unrecognized low- and high-risk patient subgroups that are over- or undertreated and lead to improved outcomes. Our EI score is a simple score that is based on recent insights into MM biology and accurately identifies high-risk and low-risk newly diagnosed MM patients as well as misclassified MM patients in different cytogenetic and ISS risk subgroups. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Application of a Validated Predictive Model for Venous Thromboembolism in Cancer to Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 534-534
Author(s):  
Natasha Catherine Edwin ◽  
Jesse Keller ◽  
Suhong Luo ◽  
Kenneth R Carson ◽  
Brian F. Gage ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Discriminative Ability ◽  
Blood Institute ◽  
C Statistic

Abstract Background Patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors (NCCN 2015, ASCO 2014, ACCP 2012). However, putative risk factors vary across guidelines and no validated VTE risk tool exists for MM. Khorana et al. developed a VTE risk score in patients with solid organ malignancies and lymphoma (Blood, 2008). We sought to apply the Khorana et al. score in a population with MM. Methods We identified patients diagnosed with MM within the Veterans Health Administration (VHA) between September 1, 1999 and December 31, 2009 using the International Classification of Diseases (ICD)-03 code 9732/3. We followed the cohort through October 2014. To eliminate patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, we excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. We also excluded patients who did not have data for hemoglobin (HGB), platelet (PLT) count, white blood count (WBC), height and weight, as these are all variables included in the Khorana et al. risk model. Height and weight were assessed within one month of diagnosis and used to calculate body mass index (BMI). We measured HGB, PLT count, and WBC count prior to treatment initiation: within two months of MM diagnosis. A previously validated algorithm, using a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement, identified patients with incident VTE after MM diagnosis (Thromb Res, 2015). The study was approved by the Saint Louis VHA Medical Center and Washington University School of Medicine institutional review boards. We calculated VTE risk using the Khorana et al. score: We assigned 1 point each for: PLT ≥ 350,000/μl, HGB < 10 g/dl, WBC > 11,000/μl, and BMI ≥ 35 kg/m2. Patients with 0 points were at low-risk, 1-2 points were considered intermediate-risk and ≥3 points were termed high-risk for VTE. We assessed the relationship between risk-group and development of VTE using logistic regression at 3- and 6-months. We tested model discrimination using the area under the receiver operating characteristic curve (concordance statistic, c) with a c-statistic range of 0.5 (no discriminative ability) to 1.0 (perfect discriminative ability). Results We identified 1,520 patients with MM: 16 were high-risk, 802 intermediate-risk, and 702 low-risk for VTE using the scoring system in the Khorana et al. score. At 3-months of follow-up, a total of 76 patients developed VTE: 27 in the low-risk group, 48 in the intermediate-risk group, and 1 in the high-risk group. At 6-months of follow-up there were 103 incident VTEs: 41 in the low-risk group, 61 in the intermediate-risk group, and 1 in the high-risk group. There was no significant difference between risk of VTE in the high- or intermediate-risk groups versus the low-risk group (Table 1). The c-statistic was 0.56 at 3-months and 0.53 at 6-months (Figure 1). Conclusion Previously, the Khorana score was developed and validated to predict VTE in patients with solid tumors. It was not a strong predictor of VTE risk in MM. There is a need for development of a risk prediction model in patients with MM. Figure 1. Figure 1. Disclosures Carson: American Cancer Society: Research Funding. Gage:National Heart, Lung and Blood Institute: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Sanfilippo:National Heart, Lung and Blood Institute: Research Funding.

scholarly journals Clinical Risk Score for the Prediction of Incident Atrial Fibrillation: Derivation in 7 220 654 Taiwan Patients With 438 930 Incident Atrial Fibrillations During a 16‐Year Follow‐Up

2021 ◽  
Author(s):  
Tze‐Fan Chao ◽  
Chern‐En Chiang ◽  
Tzeng‐Ji Chen ◽  
Jo‐Nan Liao ◽  
Ta‐Chuan Tuan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Clinical Risk Score ◽  
Clinical Risk ◽  
Asian Patients

Background Although several risk schemes have been proposed to predict new‐onset atrial fibrillation (AF), clinical prediction models specific for Asian patients were limited. In the present study, we aimed to develop a clinical risk score (Taiwan AF score) for AF prediction using the whole Taiwan population database with a long‐term follow‐up. Methods and Results Among 7 220 654 individuals aged ≥40 years without a past history of cardiac arrhythmia identified from the Taiwan Health Insurance Research Database, 438 930 incident AFs occurred after a 16‐year follow‐up. Clinical risk factors of AF were identified using Cox regression analysis and then combined into a clinical risk score (Taiwan AF score). The Taiwan AF score included age, male sex, and important comorbidities (hypertension, heart failure, coronary artery disease, end‐stage renal disease, and alcoholism) and ranged from −2 to 15. The area under the receiver operating characteristic curve of the Taiwan AF scores in the predictions of AF are 0.857 for the 1‐year follow‐up, 0.825 for the 5‐year follow‐up, 0.797 for the 10‐year follow‐up, and 0.756 for the 16‐year follow‐up. The annual risks of incident AF were 0.21%/year, 1.31%/year, and 3.37%/year for the low‐risk (score −2 to 3), intermediate‐risk (score 4 to 9), and high‐risk (score ≥10) groups, respectively. Compared with low‐risk patients, the hazard ratios of incident AF were 5.78 (95% CI, 3.76–7.75) for the intermediate‐risk group and 8.94 (95% CI, 6.47–10.80) for the high‐risk group. Conclusions We developed a clinical AF prediction model, the Taiwan AF score, among a large‐scale Asian cohort. The new score could help physicians to identify Asian patients at high risk of AF in whom more aggressive and frequent detections and screenings may be considered.

Risk Stratification in Acute Promyelocytic Leukemia Based on Elevated White Cell Count and Reduced Platelet Count Does Not Identify Subsequent Relapses: A Retrospective Review of 60 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4522-4522
Author(s):  
Richard T. Doocey ◽  
Stephen H. Nantel ◽  
Michael J. Barnett ◽  
Donna L. Forrest ◽  
Donna E. Hogge ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Maintenance Therapy ◽  
Risk Group ◽  
White Cell Count ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Risk Patients

Abstract Acute promyelocytic leukemia (APL) has become one of the more readily treatable subtypes of acute myeloid leukemia on the basis of its particular sensitivity to anthracyclines and the introduction of the differentiating agent all-trans retinoic acid (ATRA). Unfortunately some patients will ultimately relapse after achievement of complete remission. A PETHEMA and GIMEMA (PETH/GIM) cooperative group joint study sought to identify risk factors associated with relapse and developed a predictive model based on white cell count (WCC) and platelet count (Plt) at diagnosis. This model for relapse free survival was capable of segregating patients into low risk (WCC &lt; 10 x 109/L / Plt &gt; 40 x 109/L), intermediate risk (WCC &lt; 10 x 109/L / Plt &lt; 40 x 109/L), and high risk (WCC &gt; 10 x 109/L). A subsequent follow up study demonstrated improved outcomes for intermediate and high risk group patients treated with an anthracycline and ATRA based risk adapted strategy. We reviewed 60 cases of adult de novo APL treated at Vancouver General Hospital from August 1995 to December 2003. Thirty five females (58%) and 25 males (42%) were treated with a standard induction and consolidation protocol consisting of 3 cycles of Daunorubicin (60 mg/m2 OD for 3 days), Cytosine arabinoside (100 mg/m2 BID for 7 days), and ATRA (45 mg/m2/day until complete remission or a maximum of 60 days). In 2000 maintenance therapy was introduced and ATRA and/or varying doses of Methotrexate and 6-Mercaptopurine were then instituted for up to 2 years duration. At the completion of induction chemotherapy complete morphological and cytogenetic remission was achieved in 55/60 patients (92%) with 4 induction failures and only 1 death during induction treatment. Subsequently during and after consolidation and maintenance therapy at a median follow up of 34 months there were a total of 10 episodes of relapse (18%) in these 55 patients. When the 55 patients in complete remission were stratified at diagnosis by the PETH/GIM risk group there were 18 low risk patients (33%), 26 intermediate risk patients (47%), and 11 high risk patients (20%). The number of relapses was 6 in the low risk group (33%), 4 in the intermediate risk group (15%) and no relapses were identified in the high risk group. In our experience the predictive model for relapse free survival developed by the PETH/GIM cooperative group does not identify those at most likelihood for subsequent relapse after achieving an initial complete remission. The greatest number of relapse was seen in the low risk group with no relapses in the high risk group. These variations may be explained in part by the different chemotherapy treatment protocols with variable maintenance therapy. Future investigation will focus on the prognostic role of immunophenotype, additional cytogenetic abnormalities and molecular isoforms in determining outcome in APL.

Stratified follow-up for endometrial cancer: a move to more personalized cancer care

2021 ◽  
pp. ijgc-2021-002903
Author(s):  
Asma Sarwar ◽  
Jennifer Van Griethuysen ◽  
Jasmine Waterhouse ◽  
Hakim-Moulay Dehbi ◽  
Gemma Eminowicz ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
European Society ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Eligibility Criteria ◽  
Gynecology And Obstetrics

ObjectiveHospital based follow-up has been the standard of care for endometrial cancer. Patient initiated follow-up is a useful adjunct for lower risk cancers. The purpose of this study was to evaluate outcomes of endometrial cancer patients after stratification into risk groupings, with particular attention to salvageable relapses.MethodsAll patients treated surgically for International Federation of Gynecology and Obstetrics (FIGO) stage I–IVA endometrial cancer of all histological subtypes, from January 2009 until March 2019, were analyzed. Patient and tumor characteristics, treatment details, relapse, death, and last follow-up dates were collected. Site of relapse, presence of symptoms, and whether relapses were salvageable were also identified. The European Society of Medical Oncology–European Society of Gynecological Oncology 2020 risk stratification was assigned, and relapse free and overall survival were estimated.Results900 patients met the eligibility criteria. Median age was 66 years (range 28–96) and follow-up duration was 35 months (interquartile range 19–57). In total, 16% (n=144) of patients relapsed, 1.3% (n=12) from the low risk group, 3.9% (n=35) from the intermediate risk group, 2.2% (n=20) from the high–intermediate risk group, and 8.7% (n=77) from the high risk group. Salvageable relapses were less frequent at 2% (n=18), of which 33% (n=6) were from the low risk group, 22% (n=4) from the intermediate risk group, 11% (n=2) from the high–intermediate risk group, and 33% (n=6) from the high risk group. There were only three asymptomatic relapses in the low risk patients, accounting for 0.33% of the entire cohort.ConclusionsRelapses were infrequent and most presented with symptoms; prognosis after relapse remains favorable. Overall salvageable relapses were infrequent and cannot justify intensive hospital based follow-up. Use of patient initiated follow-up is therefore appropriate, as per the British Gynaecological Cancer Society's guidelines, for all risk groupings.

Preliminary Report of Risk-Based Approach in Korean Patients with Newly Diagnosed Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4911-4911 ◽  
Author(s):  
Soo-Mee Bang ◽  
Jae Hoon Lee ◽  
Sung-Soo Yoon ◽  
Seonyang Park ◽  
Je-Jung Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
Chromosome 13 ◽  
Beta 2 ◽  
The Impact

Abstract Purpose: The purpose of this study was to examine the impact of different approaches stratified on risk based on chromosome 13 deletion and serum beta-2 microglobulin (MG) level would lead to survival benefit in patients with newly-diagnosed multiple myeloma. Patients and Methods: At diagnosis, fresh marrow samples for FISH and serum for beta-2 MG were sent to central laboratory and reviewed. Patients who had chromosome 13 deletion and high beta-2 MG (&gt;2.5 mg/L) were considered to have high-risk disease. Patients without chromosome 13 deletion and low beta-2 MG were classified as low-risk group. Intermediate-risk group had to have either one of these two risk factors. After VAD induction chemotherapy, autologous stem cell transplantation conditioned with MEL200 was performed in patients at high- and intermediate-risk. DECP consolidation chemotherapy was added for high-risk patients. Patients who achieved CR after VAD in low-risk did not receive any further treatment. Results: As of Jun 2004, 50 patients were registered from 10 centers. Median age was 58 (range, 39–68) years old. Chromosome 13 deletion was detected in 18 patients (36%) and beta-2 MG was elevated in 39 patients (78%). Thirteen patients were classified as high-risk, 31 patients as intermediate-risk and 6 patients as low-risk. After median follow-up of 9 months, progression-free and overall survival at 1-year were 56% and 76%, respectively. To date, no statistically significant differences in survival were observed between risk groups (figure 1). Conclusion: In this study, risk-based approach in patients with multiple myeloma appeared to be feasible. Study accrual is ongoing and updated results will be presented. Figure Figure

Use of cytokeratin 18 and EAU score to predict tumor recurrence in patients with non-muscle-invasive bladder cancer following single postoperative immediate intravesical chemotherapy instillation.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 269-269
Author(s):  
M. Horinaga ◽  
S. Murata ◽  
M. Matsushima ◽  
Y. Nakahira ◽  
H. Yanaihara ◽  
...  
Keyword(s):  
High Risk ◽  
Scoring System ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Nuclear Staining ◽  
Intermediate Risk ◽  
Ki 67 ◽  
Risk Recurrence

269 Background: We examined the prognostic factors for recurrence after TURBT using molecular markers as well as the scoring system of the EAU. Methods: Eighty-eight patients with primary or recurrent bladder tumors who underwent TURBT followed by the single postoperative immediate instillation of pirarubicin and no further instillations were enrolled between 2003 and 2006; the median follow-up period was 46 months. The time to first recurrence was the primary end point of this study. Patients were divided into EAU recurrence risk groups as follows: low-risk group (total score, 0), intermediate-risk group (total score, 1-9) and high-risk group (total score, 9-17). The intermediate-risk group patients were subdivided into a total score of 1-4 and a total score of 5-9. Immunostaining using Ki-67, pHH3, CK18 and Survivin were performed on the TURBT specimens. Results: According to the risk stratification, 5, 82, and 1 were assigned to the low-, intermediate-, and high-risk recurrence groups, respectively. During the follow-up, recurrences were observed in 0% of the low-risk group, 45% (37 out of 82) in the intermediate-risk group and 100% in the high-risk group. We evaluated various predictors of a recurrence-free outcome among the 82 intermediate-risk patients. In univariate analyses, EAU score (1-4, 32.1% vs 5-9, 62.1%; p = 0.0011), high CK18 expression (negative, 31.4% vs positive 88.8%; p < 0.0001), high Ki-67 index (< 5%, 35.4% vs > 5%, 52.5%; p = 0.017) and high Survivin nuclear staining (< 5%, 35.9% vs > 5%, 62.5%; p = 0.004) were associated with recurrence. In a multivariate analysis, EAU score (HR 2.95, p = 0.003) and a high CK18 immunostaining (HR 6.70, p < 0.0001) were independent predictors of disease recurrence. Conclusions: A single immediate chemotherapy instillation is, by itself, insufficient for the treatment of patients in the intermediate- or high-risk recurrence groups defined by the EAU guidelines. Strong immunohistochemical expression of CK18 and the EAU scoring system appeared to be independent predictors of clinical outcome among patients with urothelial carcinoma of the bladder. No significant financial relationships to disclose.

scholarly journals SARS-CoV-2 Seroprevalence in Healthcare Workers in Germany: A Follow-Up Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4540
Author(s):  
Johannes Korth ◽  
Benjamin Wilde ◽  
Sebastian Dolff ◽  
Jasmin Frisch ◽  
Michael Jahn ◽  
...  
Keyword(s):  
High Risk ◽  
Healthcare Workers ◽  
Risk Group ◽  
Close Contact ◽  
Virus Transmission ◽  
High Risk Group ◽  
Low Risk ◽  
University Hospital ◽  
Intermediate Risk ◽  
Igg Antibody

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March–May to 4.0% in June–July to 5.1% in October–December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.

scholarly journals Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Pingfei Tang ◽  
Weiming Qu ◽  
Dajun Wu ◽  
Shihua Chen ◽  
Minji Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Pancreatic Carcinoma ◽  
Cox Regression ◽  
Risk Group ◽  
Immune Dysfunction ◽  
Low Risk ◽  
Excellent Performance ◽  
Kaplan Meier ◽  
Prognostic Prediction

Background. Acidosis in the tumor microenvironment (TME) is involved in tumor immune dysfunction and tumor progression. We attempted to develop an acidosis-related index (ARI) signature to improve the prognostic prediction of pancreatic carcinoma (PC). Methods. Differential gene expression analyses of two public datasets (GSE152345 and GSE62452) from the Gene Expression Omnibus database were performed to identify the acidosis-related genes. The Cancer Genome Atlas–pancreatic carcinoma (TCGA-PAAD) cohort in the TCGA database was set as the discovery dataset. Univariate Cox regression and the Kaplan–Meier method were applied to screen for prognostic genes. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish the optimal model. The tumor immune infiltrating pattern was characterized by the single-sample gene set enrichment analysis (ssGSEA) method, and the prediction of immunotherapy responsiveness was conducted using the tumor immune dysfunction and exclusion (TIDE) algorithm. Results. We identified 133 acidosis-related genes, of which 37 were identified as prognostic genes by univariate Cox analysis in combination with the Kaplan–Meier method ( p values of both methods < 0.05). An acidosis-related signature involving seven genes (ARNTL2, DKK1, CEP55, CTSV, MYEOV, DSG2, and GBP2) was developed in TCGA-PAAD and further validated in GSE62452. Patients in the acidosis-related high-risk group consistently showed poorer survival outcomes than those in the low-risk group. The 5-year AUCs (areas under the curve) for survival prediction were 0.738 for TCGA-PAAD and 0.889 for GSE62452, suggesting excellent performance. The low-risk group in TCGA-PAAD showed a higher abundance of CD8+ T cells and activated natural killer cells and was predicted to possess an elevated proportion of immunotherapeutic responders compared with the high-risk counterpart. Conclusions. We developed a reliable acidosis-related signature that showed excellent performance in prognostic prediction and correlated with tumor immune infiltration, providing a new direction for prognostic evaluation and immunotherapy management in PC.

Abstract 19763: Role of HAS-BLED Score on Major Bleeding in Atrial Fibrillation Undergoing Percutaneous Coronary Intervention With Drug-eluting Stents

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yoshitaka Ito ◽  
Kazuhiro Naito ◽  
Katsuhisa Waseda ◽  
Hiroaki Takashima ◽  
Akiyoshi Kurita ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Stent Implantation ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk

Background: While anticoagulant therapy is standard management for atrial fibrillation (Af), dual antiplatelet therapy (DAPT) is needed after stent implantation for coronary artery disease. HAS-BLED score estimates risk of major bleeding for patients on anticoagulation to assess risk-benefit in Af care. However, it is little known about usefulness of HAS-BLED score in Af patient treated with coronary stents requiring DAPT or DAPT plus warfarin (triple therapy: TT). The aim of this study was to evaluate the role of HAS-BLED score on major bleeding in Af patients undergoing DAPT or TT. Methods: A total of 837 consecutive patients were received PCI in our hospital from Jan. 2007 to Dec. 2010, and 66 patients had Af or paroxysmal Af at the time of PCI. Clinical events including major bleeding (cerebral or gastrointestinal bleeding) were investigated up to 3 years. Patients were divided into 2 groups based on HAS-BLED score (High-risk group: HAS-BLED score≥4, n=19 and Low-risk group: HAS-BLED score<4, n=47). DAPT therapy was required for a minimum 12 months after stent implantation and warfarin was prescribed based on physicians’ discretion. Management/change of antiplatelet and anticoagulant therapy during follow-up periods were also up to physicians’ discretion. Results: Baseline characteristics were not different between High-risk and Low-risk group except for age. Overall incidence of major bleeding was observed in 8 cases (12.1%) at 3 years follow-up. Major bleeding event was significantly higher in High-risk group compared with Low-risk group (31.6% vs. 4.3%, p=0.002). However, management of DAPT and TT was not different between the 2 groups. Among component of HAS-BLED score, renal dysfunction and bleeding contributed with increased number of the score. Conclusion: High-risk group was more frequently observed major bleeding events compared with Low-risk group in patients with Af following DES implantation regardless of antiplatelet/anticoagulant therapy.

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