Low-intermediate Risk Group Research Articles

Revised Clinical Practice Guideline of Korean Pancreatobiliary Association for Common Bile Duct Stones: Diagnosis

The diagnosis of common bile duct (CBD) stones is conducted through various imaging tests, endoscopic examinations, and the patient's clinical presentation. In patients with symptomatic gallstone disease, initial tests such as liver function tests, abdominal ultrasound, and abdominal computed tomography can be performed. Based on the results of these initial tests, symptomatic patient with cholelithiasis can be classified into low risk, intermediate risk, and high risk groups. Low risk of choledocholithiasis is characterized by normal liver function test results and absence of CBD dilation on abdominal ultrasound. For patients in this category, additional tests are not necessary unless symptoms indicating CBD stones persist. Intermediate risk of choledocholithiasis is identified by abnormal liver function test results or CBD dilation on abdominal ultrasound. Additional tests such as endoscopic ultrasound or magnetic resonance cholangiopancreatography can be performed. If CBD stones are confirmed in the additional tests, endoscopic retrograde cholangiopancreatography (ERCP) is required. High risk of choledocholithiasis is diagnosed when there is clinical evidence of cholangitis or CBD stones are identified on imaging tests. In such cases, ERCP is recommended for both diagnosis and treatment purposes without the need for further additional tests.

Assessment of lipid profile and its correlation with ASCVD risk in the general population

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major global health issue with high morbidity, mortality, and healthcare costs, emphasizing the need for effective risk assessment for prevention and management. This study aimed to assess the lipid profile of the general population and establish correlations with their ASCVD risk. Methods: This cross-sectional study was conducted among the general population in India. Participants were invited through advertisements to attend the ASCVD camp for a lipid profile check-up. Results: A total of 1068 participants were included, with a mean age of 52.7 years. The majority of participants were male (69.8%). Approximately 33% of participants had low ASCVD risk, followed by 31.6% with high risk, and 26.7% with intermediate risk. In the high ASCVD risk group, participants aged ≥60 years were significantly higher compared to those in the low risk, borderline risk and intermediate risk groups (P<0.001). The mean total cholesterol and low-density lipoprotein (LDL) were significantly increased in participants with high ASCVD risk compared to intermediate, borderline and low risk (P<0.001 and P=0.001). The mean HDL cholesterol level was significantly lower in male participants compared to female participants (P<0.001). There was a positive correlation between age (r=0.783), total cholesterol (r=0.372) and the ASCVD risk score (P<0.001 for both). There was negative correlation between HDL and ASCVD risk score (r=-124; P<0.001). Conclusion: This study demonstrates a significant association between lipid profiles and ASCVD risk. Age, total cholesterol, and LDL levels are positively correlated with ASCVD risk, while HDL levels show a negative correlation.

Application of serum tumor specific protein 70 for prognostic stratification in acute myeloid leukemia

Objective: To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML). Methods: A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping. Results: Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 (OR=2.54, 95%CI: 1.68-3.84, P<0.001), hemoglobin (HB) (OR=0.96, 95%CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) (OR=1.07, 95%CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95%CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95%CI: 0.890-0.973); C-index=0.925 (95%CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone (Z=1.693,P>0.05). Conclusion: Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

Evaluation of the prognostic value of papillary muscle-free strain in patients with hypertrophic cardiomyopathy.

The prognosis of hypertrophic cardiomyopathy (HCM) varies from mild disease with a normal life expectancy to heart failure and sudden cardiac death (SCD). The identification of patients who are at high risk for SCD remains challenging. In this study, we evaluated the prognostic value of papillary muscle-free strain in HCM patients. Seventy-nine patients with a diagnosis of HCM were included in this study. Patients were divided into low/intermediate-risk (n=57) and high-risk (n=22) groups. Two-dimensional (2-D) echocardiography and strain imaging were performed for each patient. The mean age of the study population was 53.85±15.88 years; 47 (59.5%) of them were male. During a mean follow-up duration of 74.45±17.03 months, 12 patients died. A comparison of the low-intermediate and high-SCD risk groups revealed that patients in the high-SCD risk group had greater maximal wall thickness, interventricular septum thickness, posterior wall thickness, and left ventricular mass index (LVMI) and lower (less negative) global longitudinal, anterolateral papillary muscle (ALPM) and posteromedial papillary muscle (PMPM) free strain. Additionally, a history of syncope and ICD implantation were found to be more common in patients with high SCD risk scores. The SCD risk score was positively correlated with the global longitudinal strain, ALPM-free strain, and PMPM-free strain (r=.528, r=.658, and r=.600, respectively; p<.001 for all). Our results showed that the LVMI, presence of syncope, global longitudinal strain, and ALPM-free strain were predictors of death. Decreased papillary muscle-free strain values might have prognostic value in patients with HCM.

Prognostic significance of adjuvant chemotherapy in stage I-II endometrial carcinoma patients who underwent lymphadenectomy.

Endometrial carcinoma, the most common gynecologic carcinoma, has an excellent prognosis post-surgery when diagnosed early. The role of postoperative adjuvant chemotherapy in stages I-II endometrial carcinoma remains controversial. This study assesses the efficacy of adjuvant chemotherapy in improving prognosis for these patients. A retrospective analysis was conducted on 1223 stage I-II endometrial carcinoma patients who underwent surgical treatment including total hysterectomy, bilateral salpingo-oophorectomy, and lymph-node biopsy or dissection across four Jikei University School of Medicine-affiliated facilities between 2001 and 2018. Patients were divided into low intermediate risk (LIR) and high intermediate risk (HIR) groups based on recurrence risk. Propensity score matching adjusted for various covariates was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received adjuvant chemotherapy and those who did not. The study included 443 eligible patients, with 288 in the LIR group and 155 in the HIR group. Post propensity score matching, no significant difference in PFS or OS was observed between the observation and adjuvant chemotherapy groups within both risk categories. Notably, the 5-year OS for LIR was 97.6% in the observation group and 96.7% in the chemotherapy group; for HIR, the 5-year OS was similarly high with no significant difference. The findings suggest that postoperative adjuvant chemotherapy does not significantly contribute to the improvement of recurrence or prognosis in patients with stage I-II endometrial carcinoma who are categorized outside the low-risk group and have no lymph-node metastasis.

Clinical and histopathological parameters in transrectal ultrasound-guided biopsies associated with tumor upgrading after radical prostatectomy: A comparative analysis of risk groups.

Thanks to technological advances, prostate cancer (PCa) can be diagnosed at a younger age. It is known that most of these patients are in the low-intermediate risk group, and the histological grade of the tumor increases in half of those undergoing radical prostatectomy (Rp) compared to their diagnostic biopsies. This is especially important in terms of active surveillance (AS) and/or the timely evaluation of curative treatment options in patients diagnosed at an early age. Our aim was to investigate clinical and histopathological parameters that may be associated with an increase in the histological grade of the tumor in patients with acinar adenocarcinoma who were diagnosed by transrectal ultrasound-guided biopsy (TRUS-Bx) and underwent Rp. A total of 205 patients with classical acinar adenocarcinoma diagnosed by TRUS-Bx without metastasis and who underwent Rp were grouped according to the D'Amico risk classification. Age at diagnosis, serum prostate-specific antigen (PSA), PSA density, prostate volume, Prostate Imaging Reporting and Data System (PI-RADS) score, clinical stage, Gleason Grade Group (GGG), high-grade intraepithelial neoplasia in tumor-free cores (HGPIN) (single and ≥2 cores), perineural invasion (PNI), and lymphovascular invasion (LVI) was obtained. Additionally, GGG, pathological stage, lymph node metastasis, surgical margin positivity, and tumor volume obtained from Rp were evaluated. Comparisons were made between the case groups in which the tumor grade increased and remained the same, in terms of age, serum PSA, PSA density, HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI in all biopsies (with or without tumors), as well as risk groups. In addition, the relationships of HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI on TRUS-Bx with age, serum PSA and PSA density, tumor volume, surgical margin positivity, pathological stage, lymph node metastasis, and risk groups were examined separately. Of the patients, 72 (35.1%) were in the low-risk group, 95 (46.3%) in the intermediate-risk group, and 38 (18.5%) in the high-risk group. Most of the patients with an increased histological grade (n = 38, 48.1%) were in the low-risk group (p < 0.05) and had an advanced median age. HGPIN in single and ≥2 tumor-free cores and PNI were more common in these patients (p < 0.01, p < 0.001, and p < 0.05, respectively). According to the multivariable analysis, advanced age (odds ratio [OR]: 1.087, 95% confidence interval [CI]: 1.029-1.148, p < 0.05), high serum PSA (OR: 1.047, 95% CI: 1.006-1.090, p < 0.05), HGPIN in ≥2 tumor-free cores (OR: 6.346, 95% CI: 3.136-12.912, p < 0.001), and PNI (OR: 3.138, 95% CI: 1.179-8.356, p < 0.05) were independent risk factors for a tumor upgrade. Furthermore, being in the low-risk group was an independent risk factor when compared to the intermediate- and high-risk groups (OR: 0.187, 95% CI: 0.080-0.437, p < 0.001 and OR: 0.054, 95% CI: 0.013-0.230, p < 0.001, respectively). The HGPIN diagnosis was more common in the low- and intermediate-risk groups. Advanced age at diagnosis, high serum PSA and PSA density values were associated with PNI on TRUS-Bx. High serum PSA and PSA density values were associated with LVI on TRUS-Bx. Surgical margin positivity was higher in cases with PNI and LVI detected by TRUS-Bx. HGPIN in ≥2 tumor-free cores, PNI, and LVI on TRUS-Bx were associated with a higher rate of lymph node metastases. In patients diagnosed with acinar adenocarcinoma, the presence of HGPIN even in a single tumor-free core on TRUS-Bx was found to be significant in terms of showing an increase in the histological tumor grade in Rp. The diagnosis of HGPIN in ≥2 tumor-free cores on TRUS-Bx was determined as an independent risk factor for an increased Gleason score after Rp. Furthermore, an advanced age, a high serum PSA value, being in the low-risk group, and the presence of PNI were associated with a tumor upgrade. HGPIN in ≥2 tumor-free cores, PNI, and LVI were also associated with lymph node metastasis. Therefore, the diagnosis of HGPIN should be signed out on pathological reports.

Abstract 1377: The role of TIM3 and PD1 blockades in head and neck cancer

Abstract Background: Our group has recently developed and validated a novel prognostic score for human papillomavirus (HPV+) oropharyngeal cancer called UWO3, which stratifies patients into low risk (immune rich), intermediate risk (immune mixed), and high risk (immune desert) groups. The high-risk immune desert group had a paucity of immune cells, however, that population of lymphocytes expressed high levels of the checkpoint molecule TIM3. To follow up on this, we assessed the therapeutic effect of anti-TIM3 mAb alone and in combination with anti-PD-1 in a syngenic murine HPV+ head and neck cancer model using the mERR. T-cell immunoglobulin mucin 3 (TIM3) and Programmed death 1 (PD-1) are negative immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL), play a crucial role in tumor-induced immune suppression. Given the critical role that the tumour microenvironment (TME) has on the prognosis of head and neck squamous cell carcinoma (HNSCC), immune checkpoint inhibitor immunotherapy approaches, specifically anti-PD1 and/or anti-TIM3 antibody therapy, may be very effective treatment strategies and may offer improved survival outcomes. Methods:Immunocompetent C57BL/6 mice were injected in one flank with the syngeneic mouse HPV+ cell line, mEERL (106 cells), for tumour generation. Mice were then treated with either IgG2a isotype control, anti-PD1 (200μg), anti-TIM3 (200 μg) antibodies or a combination of anti-PD-1 and anti-TIM3 were administered via intraperitoneal injection 3 times per week following tumour establishement for 6 weeks (n = 7 mice per arm, total of 28 mice). Tumour volumes were measured every 2 days. Three representative tumors from each treatment group were collected for bulk RNA sequencing, scRNA-seq, and flow cytometry to characterise immune cell populations and transcriptional changes and monitor their impact on the TME of HNSCC. Results:Anti-PD1 and anti-TIM3 both restricted tumour growth by size and weight relative to the IgG2a control (p&amp;lt;0.01, linear mixed model [lmm]). The combination of anti-PD1 and anti-TIM3 was more effective than either monotherapy alone (p&amp;lt;0.05, lmm). RNA sequencing analysis revealed differential abundance in CCL6, CCL9, CFD, and MAP3K5 transcripts relative to control for anti-PD1, anti-TIM3, and combination checkpoint inhibition. Conclusion:Targeting both PD-1 and TIM3 enhanced the anti-tumor immune response in HPV+ head and neck tumours, providing further support for dual targeting of these molecules for more effective cancer immunotherapy. Our results suggest that immune checkpoint inhibitor therapy (PD1 and TIM3 blockades) could be a promising treatment strategy for HPV+ HNSCC, and the expression of these immune checkpoint molecules could serve as a predictive biomarker of patient outcome in HPV+ HNSCC. Citation Format: Mushfiq Shaikh, Amir Karimi, Peter Zeng, Harrison Pan, John Barrett, Anthony Nichols. The role of TIM3 and PD1 blockades in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1377.

Clinical utility of CLL-IPI scoring system in Pakistani Chronic Lymphocytic Patients: A single center experience.

To determine validity of the CLL International prognostic index (IPI) scoring system in Pakistani chronic lymphocytic leukemia patients, as the validity and universal applicability of various prognostic scoring systems such as the CLL-IPI remains a challenge, particularly in under-developed countries like Pakistan. This prospective single center study was conducted at Department of Hematology, University of Health Sciences, Lahore and included sixty patients with CLL diagnosed between July, 2019 to July, 2022. Patients were followed for a period of two years and 02 year overall survival (OS) was noted. Risk stratification was conducted according to CLL-IPI prognostic model. Among 60 patients, the mean age was 60±11years. Advanced Binet stage B+C and elevated β2-microglobulin >3.5mg/L was observed in 73.3% and 38.3% patients respectively. The estimated median 02 years OS was 16.5 months (95% CI: 10-20 months). In total, 40 of 60 CLL patients (67%) were accessible for follow-up analyses. For the present CLL cohort, 25% patients (n = 10) were classified as CLL-IPI low risk and intermediate risk group, 35% (n = 14) as high risk and 15% (n = 06) as very high-risk group. However, this classification of patients according to CLL-IPI did not yield significant differences in terms of OS (p = 0.24), although the median OS of CLL-IPI very high-risk group was noted as only six months and was not reached for low and intermediate risk groups. To conclude, clinical validation of CLL-IPI scoring system could not be established for the present CLL cohort and needs to be evaluated in further studies with larger sample size.

KFRE for predicting ESRD risk in CKD 3-4 patients

Objective: The Kidney Failure Risk Equation (KFRE) is a useful tool for predicting chronic kidney disease (CKD) progression to end-stage renalkidney disease (ESRD). It has been validated in various countries populations. This study aimed to evaluate the prognostic significance of the KFRE model in a Turkish CKD cohort. Materials and Methods: In a prior retrospective study at a single center, the 4-variable KFRE model's accuracy in predicting end-stage renal disease (ESRD) progression was assessed. Among 246 stage 3 or 4 CKD individuals, two-year risk predictions categorized participants into low-intermediate (&lt;20%) and high (≥20%) risk groups. Results: The model showed a sensitivity of 48.9% (95% confidence interval [CI] 34.08–63.94) and a specificity of 89.45% (95% CI 84.32–93.35) in predicting kidney failure progression in the Turkish population with stage 3–4 CKD. The area under the receiver operating characteristic curve was 0.69 (95% CI 0.60–0.79, p = 0.0001). Albuminuria, glomerular filtration rate, and renin–aldosterone system blockage were independently associated with kidney failure progression according to the Cox regression analysis. Conclusion: The findings of this study have demonstrated that the Kidney Failure Risk Equation (KFRE) model shows potential utility in predicting the progression of stage 3–4 chronic kidney disease (CKD) toward the critical stage of end-stage renal disease (ESRD) for the Turkish population.

Preoperative Intensified Chemoradiation with Intensity-Modulated Radiotherapy and Simultaneous Integrated Boost Combined with Capecitabine in Locally Advanced Rectal Cancer: Long-Term Outcomes of a Real-Life Multicenter Study

Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. Results: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3–4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3–77.4) and 85.9% (95% CI: 80.2–90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0–13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5–26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3–5 were significantly associated with worse PFS, OS and metastasis-free survival. Conclusions: Preoperative IMRT-SIB with the moderate dose intensification of 52.5–57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.

Prognosis of Patients with Diffuse Large B Cell Lymphoma with Central Nervous System Relapse: USC Experience

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma and a potentially curable disease with systemic immunochemotherapy regimens. Involvement of the central nervous system (CNS) in patients with DLBCL is a relatively rare event which occurs in approximately 2-5% of patients overall, but the CNS relapse rate can be as high as 10-12% in high-risk patients. Unfortunately, CNS relapse confers poor prognosis with some studies estimating median survival of 2.5 months from relapse. Our study evaluates prognostic factors and outcomes in this patient population. Methods: This study is a retrospective review of patients diagnosed with DLBCL who then developed CNS relapse and were treated at Los Angeles General Medical Center (LAGMC) and Norris Comprehensive Cancer Center (NCCC) from 2016-2023. Information regarding patient demographics, prognostic factors to calculate NCCN-IPI scores, pathologic characterization, therapy, clinical course, and survival were collected. CNS relapse was defined as pathologic or imaging diagnosis of CNS involvement after initial treatment was received. Results: A total of 29 patients with CNS relapse of DLBCL were identified with a median age of 60 (range 43-86). The median time from initial diagnosis to CNS relapse was 9 months. The patients were 72.4% male (N=21), 79.3% Hispanic (N=23), and 17.2% (N=5) HIV positive. NCCN-IPI scores were calculated for all patients and divided into NCCN-IPI risk groups. The low-risk group (NCCN-IPI 0-1) made up 10.3% (N=3), low-intermediate risk group (NCCN-IPI 2-3) 48.3% (N=14), high-intermediate risk group (NCCN-IPI 4-5) 34.5% (N=10), and high-risk group (6-8) 6.90% (N=2). Pathologic analysis revealed 41.4% (N=12) of patients had germinal center type lymphoma, 44.8% (N=13) were BCL-2/c-myc double expressors, 13.8% (N=4) were BCL-2/c-myc double hit, and 13.8% (N=4) were BCL-6/c-myc double hit (Table 1). Overall survival (OS) for the entire cohort was 18.5% at five years after CNS relapse of DLBCL with a median survival of 12 months. Patients with a low or low-intermediate NCCN-IPI score (0-3) had an OS of 57.4% at 12 months and 29.1% at five years. Patients with a high-intermediate or high NCCN-IPI score had an OS of 35.7% at 12 months and 0% by 33 months. OS at 12 months for the HIV negative group was 70.4% compared to 40.0% in the HIV positive group, but OS at 5 years was similar in both groups at 19.4% and 20.0%, respectively (Figure 1). Conclusions: CNS relapse in patients with DLBCL is a rare but devastating complication. In our largely male and Hispanic patient population, prognosis at five years was very poor for those with CNS relapse, but higher NCCN-IPI scores demonstrated a trend that conferred a higher likelihood of death at both the one year and five year time points compared to those with lower scores. Survival after CNS relapse in our cohort is longer compared to prior studies, indicating possible improvements in the prognosis of patients with CNS relapse of DLBCL. Given the overall poor prognosis of CNS relapse of DLBCL, improved prognostic stratification is of the utmost importance in this highly curable disease.

Real World Population- Based Data from Nationwide Registry Support the Existence of Accelerated Phase in Newly Diagnosed Chronic Myeloid Leukemia (CML) Patients Even in Tyrosine Kinase Inhibitors (TKIs) Era

Background For decades, CML has been considered to be a triphasic disease recognizing 3 distinct stages: chronic phase (CP), accelerated phase (AP), and blast crisis (BC). Since the discovery of TKIs, the prognosis of CML patients has rapidly improved and less than 10% of patients diagnosed in CP experience disease progression on the therapy. Based on low incidence of CML progression and the fact that CML biological behavior seems biphasic, the new WHO 2022 classification of CML deemed AP less relevant and suggested the omission of AP. Many experts, however, still advocate for its inclusion in CML classification (e.g. ELN 2020, ICC 2022, NCCN 2023), even though the universal definition of AP is not established and differs in between publications. Methods This retrospective, real-world study is based on the Czech nationwide CML registry INFINITY with the data of newly diagnosed CML patients who agreed and provided their written consent. Recruited subjects were adult patients diagnosed in years 2005 - 2022 with sufficient data to determine the phase of the disease at diagnosis and follow-ups to assess their overall survival (OS), disease specific survival (DSS) and progression-free survival (PFS). The phase of the disease at the time of diagnosis was determined using the classification according to ELN 2020, ICC 2022, WHO 2016, and WHO 2022. Whenever CP was established, EUTOS Long-Term Survival (ELTS) score was calculated, assigning the patient to low risk (LR), intermediate risk (IR) and high risk (HR) group. OS and PFS are defined according to published guidelines. DSS is defined as the time from diagnosis to death due to CML disease or CML treatment. Results During the studied time period, 1660 new cases of CML were reported in INIFINITY registry. Of them, 1500 patients had data sufficient to classify the phase of the disease at the time of the diagnosis according to ELN 2020 guidelines and WHO 2022 classification and 1395 patients had data to assess the phase according to WHO 2016 and ICC 2022 classifications. When using ELN 2020 guidelines, groups were assigned as follows: LR CP- 784 patients (52.3%), IR CP- 421 patients (28.1%), HR CP- 227 patients (15.1%), AP- 42 patients (2.8%), BC- 26 patients (1.7%). There were significant differences in representation by gender, age, comorbidities and performance score amongst patient groups. When comparing just HR CP and AP CML patients, there were no significant differences. Calculated estimates of 5- and 10- year OS, respectively, were 92.5% and 87.2% for LR CP, 83.5% and 65.9% for IR CP, 76.9% and 65.5% for HR CP, 59.2% and 45.9% for AP, and 32.9% for BC, p= 0.031 for HR CP versus AP (Figure 1). In the case of WHO 2016 and ICC 2022 classifications, 714 (51.2%) patients were diagnosed in LR CP, 374 (26.8%) in IR CP, 154 (11.0%) in HR CP, 125 (9.0%) in AP, and 28 (2.0%) in BC. Again, there were significant differences in representation by gender, age, comorbidities and performance score amongst patient groups. When comparing just HR CP and AP CML patients, only age at the time of diagnosis was significantly different. Calculated estimates of 5- and 10- year OS, respectively, were 93.2% and 87.5% for LR CP, 84.9% and 67.7% for IR CP, 80.0% and 69.5% for HR CP, 65.7% and 55.6% for AP, and 39.7% for BC. We also performed propensity score matching according to age for patients in HR CP and AP and calculated estimates of 5- and 10- year OS, respectively, were 85.4% and 74.4% for HR CP and 60.2%, and 52.0% for AP, p= 0.003 (Figure 2). Similar results were obtained when testing for PFS and DSS. Summary Real-world data obtained from 1500 patients diagnosed in Czechia over 17 years, in our opinion, support the need to recognize the existence of AP at the time of diagnosis, even though a singular definition of AP is not agreed upon. Patients in AP have worse survival scores (OS, DSS, PFS) compared to patients in CP and/or HR CP. Moreover, because ELTS risk score was calculated on patients in CP, it may not be suitable for patients in AP, which would be changed to CP according to the new WHO 2022 classification. In conclusion, based on the real-world data with long-term follow-up, we believe it would be reasonable to keep the AP as part of CML classification of newly diagnosed patients. This publication was supported by the grant number MUNI/A/1224/2022, Programme EXCELES, ID Project No. LX22NPO5102, and by the Ministry of Health of the Czech Republic grant number 00023736.

Accuracy of the GRACE Score for mortality prediction in myocardial infarction with nonobstructive coronary arteries (MINOCA)

Abstract Introduction Myocardial infarction with nonobstructive coronary arteries (MINOCA) patients account for 3.5 to 15% of all myocardial infarctions. The GRACE risk score is a well-validated tool for estimating short- and long-term risk in acute coronary syndrome, but the accuracy of the risk score for prognostic stratification in patients with MINOCA remains uncertain. Purpose We aimed to investigate whether the GRACE risk score can predict mortality in a real-world cohort of patients presenting with MINOCA. Methods We retrospectively analyzed patients admitted with MINOCA in a single center. Patients who were diagnosed with myocarditis and Takotsubo syndrome were excluded from the analysis. The GRACE risk score on admission was calculated. Patients were divided into a low-intermediate risk group (≤ 140 points, 71.5%) and a high-risk group (&amp;gt;140 points, 28.5%) according to their GRACE risk scores. Receiver operating characteristic (ROC) analysis was used to quantify the accuracy of the GRACE risk score to estimate both in-hospital and one-year mortality in MINOCA patients. Results Of a total of 3721 myocardial infarction patients, MINOCA was identified in 11.6% (n=430). 313 patients had complete data for the calculation of the GRACE on admission and were included in the analysis. Mean age was 65±12 years, and 49% (n=154) of patients were male. Mean GRACE score was 125±31 points. Patients in the high-risk group were older (74±9 vs. 61±11 years, p&amp;lt;0.001), had a higher incidence of in-hospital mortality (0.4% vs. 5.6%, p=0.008), and had a higher rate of one-year mortality (2.7% vs. 19.5%, p&amp;lt;0.001), compared with the low-intermediate risk group. There were no differences regarding sex and cardiovascular risk factors between the groups. In-hospital mortality was 1.9% and one-year mortality was 7.3%. ROC curve analysis showed that the GRACE risk score has a high value in predicting in-hospital mortality (AUC ROC 0.892; 95% CI 0.798–0.986; p=0.001), and one-year mortality (AUC ROC 0.826; 95% CI 0.739–0.0.914; p&amp;lt;0.001) in MINOCA patients. (Figure 1). The overall c-statistics were similar compared with estimates obtained from patients with myocardial infarction and significant coronary artery disease: in-hospital mortality (AUC ROC 0.0.849; 95% CI, 0.807–0.891; p&amp;lt;0.001); and one-year mortality (AUC ROC 0.776; 95% CI, 0.747–0.806; p&amp;lt;0.001). Conclusions In conclusion, the GRACE risk score provides potentially valuable prognostic information on in-hospital and one-year mortality when applied to MINOCA patients.Figure 1

Characteristics of genetic variants in 134 patients with Acute myeloid leukemia

To analyze the characteristics of genetic variants in 134 patients diagnosed with Acute myeloid leukemia (AML). Clinical data of the 134 patients with AML (non-acute promyelocytic leukemia) initially diagnosed at the 940th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from June 2017 to June 2022 were retrospectively analyzed. Potential variants of AML-related genes were detected by next-generation sequencing, and the frequency of variants was analyzed by using SPSS v26.0 software, and likelihood ratio χ2 test and Fisher exact test were used for data analysis. The patients had included 72 males and 62 females, with a gender ratio of 1.7 : 1 and a median age of 51 years (9 ~ 86 years old). One hundred twenty patients (76.1%) had harbored at least one genetic variant, including 26 (19.4%) having a single variant, 27 (20.1%) having two variants, and 49 (36.6%) having >= 3 variants. 32 (23.9%) had no detectable variants. Genetic variants detected in over 10% of the 134 patients had included NPM1 (n = 24, 17.91%), FLT3-ITD (n = 21, 15.67%), DNMT3A (n = 20, 14.93%), CEBPA (single variant; n = 14, 10.45%), TET2 (n = 14, 10.45%), and NRAS (n = 14, 10.45%). The patients were also divided into low risk, intermediate risk and high risk groups based on their chromosomal karyotypes. The mutational rates for genes in different groups have varied, with 19 patients from the low risk group harboring variants of NRAS (n = 4, 21.05%), KRAS (n = 4, 21.05%), and KIT (n = 2, 10.53%); and 96 patients from the intermediate risk group harboring variants of NPM1 (n = 24, 25.00%), FLT3-ITD (n = 20, 20.83%), DNMT3A (n = 18, 18.75%), CEBPA (n = 12, 12.50%), and TET2 genes (n = 12, 12.50%). The mutational frequencies for the 19 patients from the high risk group were ASXL1 (n = 7, 21.05%), NRAS (n = 3, 15.97%), TP53 (n = 3, 15.79%), and EZH2 (n = 2, 10.53%). A significant difference was found in the frequencies of KIT, NPM1, FLT3-ITD, DNMT3A, and ASXL1 gene variants among the low-risk, medium-risk, and high-risk groups. AML patients have a high frequency for genetic variants, with 76.1% harboring at least one variant. The frequency of genetic variants have varied among patients with different chromosomal karyotypes, and there are apparent dominant variants. KIT, NPM1, FLT3-ITD, DNMT3A, and ASXL1 may be used as prognostic factors for evaluating their prognosis.

The role of Mangled Extremity Severity Score in amputation triage in a transport health facility with catastrophic earthquake admissions

BackgroundThe purpose of this study is to assess the diagnostic utility of the Mangled Extremity Severity Score (MESS) in the prediction of amputation after a major earthquake, and its utility in disaster triage. MethodsStudy results were presented from a tertiary hospital in Diyarbakır, which was affected by the earthquake but served as a transport hub for other cities in the region affected by the earthquake. MESS was calculated and its diagnostic value is analyzed in predicting amputations. MESS scores were divided into low risk, intermediate risk, and high risk groups by the researchers based on their diagnostic value analysis. Results79 patients were included in the study. Based on the outcome of amputation or salvage, patients were divided into two groups. 24.1% (n = 19) of the patients had amputations. Both gender and mean age did not differ statistically significantly between the groups (p > 0.05). Compared with the salvage group, the amputation group had a significantly longer prehospital stay and higher rate of vascular injury and higher median MESS (p = 0.007, p < 0.001, p < 0.001; respectively). Based on MESS scores, amputation outcomes were predicted with an accuracy of 0.889 (95% CI 0.798–0.949). Those with a MESS score below 9 were considered low risk (sensitivity = 100%) whereas those with a MESS score above 12 were considered high risk (specificity = 98.33%). ConclusionIn transport centers, MESS may be useful for surgical triage of earthquake-induced limb crush injuries.

#5802 ASSESSMENT OF THE INTERNATIONAL IGA NEPHROPATHY PREDICTION TOOL AFTER IGAN TREATMENT: A CASE-SERIES STUDY

Abstract Background and Aims IgAN have a variable clinical course and a considerable risk of ESKD. The 2021 KDIGO guidelines recognize the International IgAN Prediction Tool (IIgAN-PT) as a quantifier of progression risk at the time of kidney biopsy. The possible application of the IIgAN-PT to re-evaluate the risk after treatment and during follow-up is debated. We analyzed the possible association between treatment response and changes of IIgAN-PT risk estimation. Method Retrospective study including patients with IgAN undergone kidney biopsy from Jan 2010 to Dec 2020. Inclusion criteria: treatment with glucocorticoids, age&amp;gt;18, follow-up at 3-6-12-24 months, availability of risk assessment. Progression risk evaluated by IIgAN-PT at time 0 (biopsy) and after 6-12 months. Two risk groups were identified based on the IIgAN-PT at time 0: Low-Intermediate risk group (Low-risk, IIgAN-PT&amp;lt;23%) and High-risk group (High-risk; IIgAN-PT risk≥23%). Results A total of 22 patients were included (59% Low-risk; 31% High-risk). Patients at low- risk had significantly higher eGFR with respect to high-risk group (78 vs 40 ml/min/1.73 m² respectively) (p&amp;lt;0.001). Age, MAP, and RASi use at biopsy did not differ significantly. Proteinuria was comparable among groups: 3.14 g/24 h in High-risk and 2.49 g/24h in Low-risk (p = 0.17). In the Low-risk group the median proteinuria swiftly decays below 1.0 g/day already at three months, and below 0.5 g/day after six. Conversely, in the high-risk group, it remained above 1 g/day until 12 months (Fig. 1). Regarding risk progression assessment: 89% of patients at higher risk at baseline became at lower risk at 6 months (Fig 2; Table 1). Conclusion Treatment response was associated with a reduction in the IgAN progression risk as demonstrated by changing of IIgAN-PT already after 6 months. These data suggest a possible dynamic use of IIgAN-PT for IgAN progression risk re-evaluation even in the short follow-up period.

New biomarkers in peripheral artery disease cardiovascular rehabilitation - keep it simple

Abstract Funding Acknowledgements Type of funding sources: None. Cardiac rehabilitation (CR) plays an essential role in the management of patients with peripheral artery disease (PAD) [1]. Patients enrolment in an integrative and multidisciplinary program, can improve the functional status, quality of life, and long-term morbidity and mortality [2]. We conducted a prospective cohort study on 97 patients with PAD admitted to a single tertiary referral center. Based on a long-term mortality prognostic index in PAD [3], we enrolled two groups of patients: low and low-intermediate risk (group 1, n=45) versus high-intermediate and high risk (group 2, n=52). We analyzed demographics, clinical, and paraclinical parameters, focusing on novel inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), white blood cells-to-MPV ratio (WMR) and lymphocyte-to-C-reactive protein ratio (LCR). The 6 months follow-up showed that a minimum 50% decrease compared to initial levels was associated with both short and long-term clinical and functional improvement. A decrease in NLR (p &amp;lt; 0.001), PLR (p = 0.028), WMR (p = 0.009) and LCR (p = 0.036) levels correlated positively with improved metabolic profile - low-density lipoprotein cholesterol (p= 0.015), triglycerides (p= 0.041) , fasting glucose (p=0.011) -, as well as improved exercise capacity - assessed through peak oxygen uptake (p = 0.008), pain-free walking distance (p = 0.024) and maximum walking distance (p = 0.032) at 6 months follow-up for group 1. Assessment of these inflammatory biomarkers had a statistically significant prognostic role in our study, being an accessible tool for clinical cardiologists in evaluating CR programs effectiveness in patients with PAD.

Anatomical and anastomotic viability indexes for stratifying the risk of anastomotic leakage in esophagectomy with retrosternal reconstruction.

Risk prediction of anastomotic leakage using anatomical and vascular factors has not been well established. This study aimed to assess the anatomical and vascular factors affecting the hemodynamics of the gastric conduit and develop a novel risk stratification system in patients undergoing esophagectomy with retrosternal reconstruction. This retrospective cohort study analyzed 202 patients with esophageal cancer who underwent subtotal esophagectomy with gastric tube retrosternal reconstruction between January 2008 and December 2020. Risk factors for anastomotic leakage (AL), including the anatomical index (AI) and anastomotic viability index (AVI), were evaluated using a logistic regression model. According to the logistic regression model, the independent risk factors for AL were preoperative body mass index ≥23.6 kg/m2 (odds ratio [OR], 7.97; 95% confidence interval [CI], 2.44-26.00; P < 0.01), AI <1.4 (OR, 23.90; 95% CI, 5.02-114.00; P < 0.01), and AVI <0.62 (OR, 8.02; 95% CI, 2.57-25.00; P < 0.01). The patients were stratified into four AL risk groups using AI and AVI as follows: low-risk group (AI ≥1.4, AVI ≥0.62 [2/99, 2.0%]), intermediate low-risk group (AI ≥1.4, AVI <0.62 [2/29, 6.9%]), intermediate high-risk group (AI <1.4, AVI ≥0.62 [8/53, 15.1%]), and high-risk group (AI <1.4, AVI <0.62 [11/21, 52.4%]). The combination of AI and AVI strongly predicted AL. Additionally, the use of AI and AVI enabled the stratification of the risk of AL in patients who underwent esophagectomy with retrosternal reconstruction.

Genetically-Determined LDL Negatively Impacts Clinical Evolution of Ischemic Stroke Survivors (S3.003)

<h3>Objective:</h3> We aim to study the contribution of genetically-determined lipid levels to the clinical trajectories of stroke survivors. <h3>Background:</h3> Ischemic Stroke survivors are at high risk of stroke recurrence. Understanding the genetic risk factors for stroke recurrence will help guide future prevention strategies. <h3>Design/Methods:</h3> We analyzed clinical and genetic data from the Vitamin Intervention Stroke Prevention (VISP) clinical trial, which examined high-dose vitamins in stroke survivors. Genetic susceptibility to increased LDL-c was modeled through a polygenic risk score built with genetic data on 38 known genetic risk variants for LDL-cholesterol (variants influencing other lipid traits were excluded). We divided the LDL-related polygenic risk score into 0–20, 20–80, and 80–100 percentile categories labeled as low, intermediate and high genetic predisposition to high LDL. We fitted multivariable (adjusting for age, sex, vascular risk factors, and statin treatment) Cox proportional hazards and logistic regression models to test whether higher polygenic risk for elevated LDL-c was associated with observed LDL-c, ischemic stroke recurrence, and composite risk of ischemic stroke and myocardial infarction. <h3>Results:</h3> Of the 2,164 stroke survivors enrolled in VISP, 1,567 (72%) had available LDL-c and genetic data. The mean LDL in the low, intermediate and high polygenic risk categories was 114.5 (SD 2.21), 123.2 (SD 1.23), and 128.8 (SD 2.35), respectively (unadjusted p&lt;0.001). Compared to stroke survivors with low polygenic risk, intermediate (HR 1.52, 95% CI 0.91–2.54) and high (HR 2.03, 95% CI 1.14–3.61) polygenic risk groups had significantly higher stroke recurrence risk (p test-for-trend 0.01). We observed similar associations when evaluating the composite risk of stroke and myocardial infarction (all p&lt;0.05). <h3>Conclusions:</h3> A higher polygenic risk for increased LDL-c is associated with worse clinical trajectories after stroke. Further research is needed to determine whether stroke survivors with an elevated genetic risk benefit from unique care pathways with additional monitoring and treatment. <b>Disclosure:</b> An immediate family member of Mr. Wu has received personal compensation for serving as an employee of Bristol-Myers Squibb. Mr. Wu has received research support from NIH. Dr. Rivier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pyxis Partners. Mr. Demarais has nothing to disclose. Ms. Conlon has nothing to disclose. Dr. Renedo has nothing to disclose. Mr. Torres-Lopez has nothing to disclose. Dr. Sharma has nothing to disclose. Dr. De Havenon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Integra. Dr. De Havenon has stock in Certus. The institution of Dr. De Havenon has received research support from NIH/NINDS. The institution of Dr. De Havenon has received research support from Regeneron Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMAG Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMGEN. Dr. De Havenon has received publishing royalties from a publication relating to health care. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zoll. Dr. Sheth has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NControl. Dr. Sheth has received stock or an ownership interest from Astrocyte. Dr. Sheth has received stock or an ownership interest from Alva. The institution of Dr. Sheth has received research support from Biogen. The institution of Dr. Sheth has received research support from Novartis. The institution of Dr. Sheth has received research support from Bard. The institution of Dr. Sheth has received research support from Hyperfine. Dr. Sheth has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Falcone has received research support from NIH. The institution of Dr. Falcone has received research support from AHA.

Mutational Spectrum and Prognosis Analysis of Young Patients with Diffuse Large B-Cell Lymphoma Based on Next-Generation Sequencing

To investigate the mutational spectrum in young patients with diffuse large B-cell lymphoma (DLBCL) based on next generation sequencing (NGS), and to provide a basis for in-depth understanding of the molecular biological characteristics and accurate prognosis of young DLBCL. From March 2009 to March 2021, 68 young DLBCL patients with complete initial diagnosis data from the Department of Hematology, The People's Hospital Xinjiang Uygur Autonomous Region were retrospectively analyzed, and their paraffin-embedded tissues were subjected to targeted sequencing analysis by NGS technology (including 475 Target genes), and the differences in gene mutation profiles and signaling pathways between high-risk patients with aaIPI ≥2 and low-intermediate risk patients with aaIPI <2 were compared. A total of 44 high-frequency mutation genes were detected in 68 young DLBCL patients. By comparing the high-frequency mutation genes in aaIPI high-risk group and low-intermediate risk group, it was found that CARD11 mutation in aaIPI high-risk group was significantly higher than that in low-intermediate risk group (P =0.002), while MGA mutation (P =0.037) only appeared in the aaIPI high-risk group, and SPEN mutation (P =0.004) only appeared in the aaIPI low-intermediate risk group. The high-frequency mutation genes and clinical indicators of the aaIPI high-risk group were included in the survival analysis, and the results showed that TP53 (P =0.009, P =0.027), POU2AF1 (P =0.003, P =0.006) and CCND3 (P =0.040, P =0.014) genes mutations were associated with worse PFS and OS, while B2M was associated with better PFS (P =0.014) and OS (P =0.013). Multivariate COX regression analysis showed that the TP53, POU2AF1 and CCND3 were independent risk factors for PFS（P ＝0.021，P =0.005，P =0.020） and OS（P ＝0.042，P =0.010，P =0.013）. The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. TP53, POU2AF1 and CCND3 mutations predict worse survival in the patients with the aaIPI high-risk group.