Mechano-inhibition of endocytosis sensitizes cancer cells to Fas-induced Apoptosis.

The transmembrane death receptor Fas transduces apoptotic signals upon binding its ligand, FasL. Although Fas is highly expressed in cancer cells, insufficient cell surface Fas expression desensitizes cancer cells to Fas-induced apoptosis. Here, we show that the increase in Fas microaggregate formation on the plasma membrane in response to the inhibition of endocytosis sensitizes cancer cells to Fas-induced apoptosis. We used a clinically accessible Rho-kinase inhibitor, fasudil, that reduces endocytosis dynamics by increasing plasma membrane tension. In combination with exogenous soluble FasL (sFasL), fasudil promoted cancer cell apoptosis, but this collaborative effect was substantially weaker in nonmalignant cells. The combination of sFasL and fasudil prevented glioblastoma cell growth in embryonic stem cell-derived brain organoids and induced tumor regression in a xenograft mouse model. Our results demonstrate that sFasL has strong potential for apoptosis-directed cancer therapy when Fas microaggregate formation is augmented by mechano-inhibition of endocytosis.

Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The US Myeloma Immunotherapy Consortium Real- World Experience.

Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.S. Impact of ALC parameters including pre-apheresis (pre-A), pre-lymphodepletion (pre-LD), absolute and percent difference from pre-A to pre-LD on clinical outcomes after ide-cel were examined using survival analysis. A new ALC profile was created based on univariate analysis that comprises 3 groups: normal (≥1 × 109/L) pre-LD ALC (LDN), low (<1 × 109/L) pre-LD ALC (LDL) + percent reduction <37.5 (%RL), and LDL ALC + percent reduction ≥37.5 (%RH). A total of 214 SOC ide-cel recipients were included in this analysis. The median patient age was 64 years (interquartile range [IQR], 57 to 69 years), median number of prior therapies was 6 (IQR, 5 to 9), and median duration of follow-up was 5.4 months (IQR, 2.1 to 8.3 months). Most patients had both low pre-A ALC (75.3%) and pre-LD ALC (77.2%), and the reduction from pre-A to pre-LD (median, .65 to .55 × 109/L) was statistically significant. Univariate analysis showed that the LDL + %RH group had significantly worse progression-free survival (PFS) and overall survival (OS) compared to the LDL + %RL and LDN ALC groups (6-month PFS: 40% versus 67.6% and 60.9%; 6-month OS: 69.5% versus 87% and 94.3%). In multivariable analysis, after adjusting for age, performance status, cytogenetic risk, use of bridging therapy, and extramedullary disease, PFS did not maintain its statistical significance; however, OS remained significantly worse for LDL + %RH group compared to the LDN ALC group (hazard ratio [HR], 4.3; 95% confidence interval [CI], 1.1 to 17), but the difference between the LDL + %RH versus %RL groups was not statistically significant (HR, 1.7; 95% CI, .8 to 4.0). Our findings indicate that low pre-LD ALC with high %R from pre-A to pre-LD was associated with inferior survival outcomes, particularly OS, in patients who received SOC ide-cel.

Endothelial injury and dysfunction with emerging immunotherapies in multiple myeloma, the impact of COVID-19, and endothelial protection with a focus on the evolving role of defibrotide.

Patients with multiple myeloma (MM) were among the groups impacted more severely by the COVID-19 pandemic, with higher rates of severe disease and COVID-19-related mortality. MM and COVID-19, plus post-acute sequelae of SARS-CoV-2 infection, are associated with endothelial dysfunction and injury, with overlapping inflammatory pathways and coagulopathies. Existing treatment options for MM, notably high-dose therapy with autologous stem cell transplantation and novel chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engaging antibodies, are also associated with endothelial cell injury and mechanism-related toxicities. These pathologies include cytokine release syndrome (CRS) and neurotoxicity that may be exacerbated by underlying endotheliopathies. In the context of these overlapping risks, prophylaxis and treatment approaches mitigating the inflammatory and pro-coagulant effects of endothelial injury are important considerations for patient management, including cytokine receptor antagonists, thromboprophylaxis with low-molecular-weight heparin and direct oral anticoagulants, and direct endothelial protection with defibrotide in the appropriate clinical settings.

A Clinical Perspective on Plasma Cell Leukemia: A Single-Center Experience.

Circulating plasma cells (CPCs) are detected in most multiple myeloma (MM) patients, both at diagnosis and on relapse. A small subset, plasma cell leukemia (PCL), represents a different biology and has a poor prognosis. In this retrospective analysis, we evaluated patients with primary (pPCL, n = 35) or secondary (sPCL, n = 49), with ≥5% CPCs and a smaller subset with lower CPCs of 1-4% (n = 20). The median age was 61 years; 45% were men and 54% were Black. High-risk cytogenetics were found in 87% and extramedullary disease in 47%. For the entire cohort, 75% received a proteasome inhibitor, 70% chemotherapy, 54% an immunomodulatory drug, 24% a daratumumab-based regimen and 26% an autologous stem cell transplant (ASCT). The treatments marginally improved the overall survival (OS) for pPCL vs. sPCL (13 vs. 3.5 months p = 0.002). However, the 5-year survival for the whole cohort was dismal at 11%. High-risk cytogenetics, low platelets, extramedullary disease and high LDH were independently associated with poor outcomes. Further research is urgently needed to expand the treatment options and improve the outcomes in PCL.

Can direct bilirubin-to-lymphocyte ratio predict surgery for pediatric adhesive small bowel obstruction?

OBJECTIVE: Estimating which patients might require surgical intervention is crucial. Patients with complete bowel obstructions exhibit disrupted enterohepatic cycles of bile and bacteremia due to bacterial translocation. The goal of this study was to develop a prediction index using laboratory inflammatory data to identify patients who may need surgery. MATERIALS AND METHODS: The patients were divided into two groups based on their management strategy: Non-operative management (Group 1) and surgical management (Group 2). RESULTS: The indirect bilirubin, direct bilirubin, and total bilirubin were significantly higher in Group 2 than in Group 1 (p = 0.001, p < 0.001, and p < 0.001, respectively). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-NLR (PNLR), and direct bilirubin-to-lymphocyte ratio (DBR) were significantly higher in Group 2 compared to Group 1 (p = 0.041, p = 0.020, and p < 0.001, respectively). In group 2, 78% have viable bowels. Resection was performed in 40% of cases, with 12% mortality and a 10-day average hospital stay. DLR performs the best overall accuracy (72%), demonstrating a well-balanced sensitivity (62%) and specificity (81%). CONCLUSIONS: This study suggested that DBR is a more accurate predictive index for surgical intervention in pediatric adhesive small bowel obstruction patients compared to NLR and PNLR, providing valuable guidance for treatment strategies.

OBJETIVO: Desarrollar un índice de predicción utilizando datos inflamatorios de laboratorio para identificar qué pacientes podrían necesitar cirugía. MÉTODO: Los pacientes se dividieron en dos grupos según su estrategia de manejo: no quirúrgico (grupo 1) o quirúrgico (grupo 2). RESULTADOS: Las bilirrubinas indirecta, directa y total fueron significativamente más altas en el grupo 2 que en el grupo 1 (p = 0.001, p < 0.001 y p < 0.001, respectivamente). Las relaciones neutrófilos-linfocitos, plaquetas-neutrófilos-linfocitos y bilirrubina directa-linfocitos fueron significativamente más altas en el grupo 2 que en el grupo 1 (p = 0.041, p = 0.020 y p < 0.001, respectivamente). En el grupo 2, el 78% tenían intestino viable. Se realizó resección en el 40% de los casos, con un 12% de mortalidad y una estancia hospitalaria promedio de 10 días. La relación bilirrubina directa-linfocitos tuvo la mejor precisión general (72%), demostrando una sensibilidad bien equilibrada (62%) y una buena especificidad (81%). CONCLUSIONES: Este estudio sugiere que la relación bilirrubina directa-linfocitos es un índice predictivo más preciso para la intervención quirúrgica en pacientes pediátricos con obstrucción adhesiva de intestino delgado en comparación con la de neutrófilos-linfocitos y la de plaquetas-neutrófilos-linfocitos, proporcionando una valiosa orientación para las estrategias de tratamiento.

Protective effects of Passiflora Incarnata on ischemia-reperfusion injury in testicular torsion: an experimental study in a rat model.

OBJECTIVE: The current study aimed to explore the potential protective effect of Passiflora Incarnata L., (PI) in treating IR injury after testicular torsion in rats. MATERIALS AND METHODS: This research investigated the impact of PI on IR damage in male Wistar albino rats. Animals were divided to three groups: group 1 (sham), group 2 (IR), and group 3 (IR+PI). RESULTS: The malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels did not significantly differ across the groups (p = 0.830, p = 0.153 and p=0.140, respectively). However, Group 3 demonstrated a superior total antioxidant status (TAS) value compared to Group 2 (p = 0.020). Concurrently, Group 3 presented a significantly diminished mean total oxidant status (TOS) relative to Group 2 (p = 0.009). Furthermore, Group 3 showed a markedly improved Johnsen score relative to Group 2 (p < 0.01). IR caused cell degeneration, apoptosis, and fibrosis in testicular tissues. PI treatment, however, mitigated these effects, preserved seminiferous tubule integrity and promoted regular spermatogenesis. Furthermore, it reduced expression of tumor necrosis factor-alpha (TNF-α), Bax, and Annexin V, signifying diminished inflammation and apoptosis, thereby supporting cell survival (p < 0.01, p < 0.01, p < 0.01, respectively). CONCLUSIONS: This study revealed that PI significantly reduces oxidative stress and testicular damage, potentially benefiting therapies for IR injuries.

OBJETIVO: Explorar el posible efecto protector de Passiflora incarnata L. (PI) en el tratamiento de la lesión por isquemia-reperfusión (IR) después de una torsión testicular en ratas. MÉTODO: Se estudió el impacto de Passiflora incarnata en el daño por IR en ratas Wistar albinas machos. Los animales se dividieron tres grupos: 1 (simulado), 2 (IR) y 3 (IR+PI). RESULTADOS: Los niveles de malondialdehyde (MDA), myeloperoxidase (MPO) y glutathione (GSH) no difirieron significativamente entre los grupos (p = 0.830, p = 0.153 y p = 0.140, respectivamente). Sin embargo, el grupo 3 tuvo un valor de estado antioxidante total (TAS) superior en comparación con el grupo 2 (p = 0.020). Al mismo tiempo, el grupo 3 presentó un estado oxidante total (TOS) medio significativamente disminuido en comparación con el grupo 2 (p = 0.009). El grupo 3 mostró una mejora notable en la puntuación de Johnsen en comparación con el grupo 2 (p < 0.01). La IR causó degeneración celular, apoptosis y fibrosis en los tejidos testiculares. El tratamiento con PI mitigó estos efectos, preservó la integridad de los túbulos seminíferos y promovió la espermatogénesis regular. Además, redujo la expresión de factor de necrosis tumoral alfa, Bax y anexina V, lo que significa una disminución de la inflamación y de la apoptosis, respaldando así la supervivencia celular (p < 0.01, p < 0.01 y p < 0.01, respectivamente). CONCLUSIONES: Este estudio reveló que PI reduce significativamente el estrés oxidativo y el daño testicular, beneficiando potencialmente las terapias para lesiones por IR.

Prehabilitation Maximizing Functional Mobility in Patients With Cardiogenic Shock Supported on Axillary Impella.

Physical therapy (PT) benefits for critically ill patients are well recognized; however, little data exist on PT in patients receiving temporary mechanical circulatory support. In this single-center retrospective study (February 2017-January 2022), we analyzed 37 patients who received an axillary Impella device (Abiomed, Danvers, MA) and PT to "prehabilitate" them before durable left ventricular assist device (dLVAD) implantation. The Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility tool assessed the functional status at different points during admission. Immediately after Impella placement, the median AM-PAC score was 12.7 (interquartile range [IQR], 9-15), and the scores continued to significantly increase to 18.4 (IQR, 16-23) before dLVAD and up to 20.7 (IQR, 19-24) at discharge, indicating improved independence. No PT-related complications were reported. Thus, we hypothesize that critically ill patients initially deemed equivocal candidates may safely participate in PT while maximizing functional activities before dLVAD placement.

Racial and ethnic differences in clinical outcomes among patients with multiple myeloma treated with CAR T-cell therapy.

ABSTRACT: Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) non-Hispanic Black, and 149 (72%) non-Hispanic White patients with RRMM. Compared with Hispanic and non-Hispanic White patients, non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P = .02) and baseline ferritin (362.0 vs 307.0 vs 680.5, respectively; P = .08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P = .04). Although best overall response rate was lower among Hispanic patients (59%) than among non-Hispanic Black (86%) and White patients (86%; P = .01), there were no racial and ethnic differences in progression-free or overall survival. We provide, to our knowledge, the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all patients with RRMM. These findings should be confirmed in larger samples of diverse patients with RRMM, with longer follow-up time.

Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment.

We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population. RI was defined as creatinine clearance (CrCl) <50 mL/min. CrCl of <30 mL/min or dialysis dependence were defined as severe RI. The study cohort included 214 patients, 28 (13%) patients with RI, including 11 patients severe RI (dialysis, N=1). Patients with RI were older, more likely to be female and had higher likelihood of having Revised International Staging System stage 3 disease. Rates and severity of cytokine release syndrome (89% vs. 84%, grade ≥3: 7% vs. 2%) and immune effector cell-associated neurotoxicity syndrome (23% vs. 20%) were similar in patients with and without RI, respectively. Patients with RI had higher incidence of short-term grade ≥3 cytopenias, although cytopenias were similar by 3 months following CAR T-cell therapy. Renal function did not worsen after CAR T-cell therapy in patients with RI. Response rates (93% vs. 82%) and survival outcomes (median progression-free survival: 9 vs. 8 months; P=0.26) were comparable in patients with and without RI, respectively. Treatment with ide-cel is feasible in patients with RI, with a comparable safety and efficacy profile as patients without RI, with notable exception of higher short-term high-grade cytopenias.

Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma: U.S. Myeloma Immunotherapy Consortium real world experience.

While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted CAR T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤ 3 months after CAR T infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event ≤ 3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress ≤ 3 months of infusion (p < 0.05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (p < 0.001; median PFS for ≥ 3 factors, 3.2 months vs. 0 factors, 14.1 months). This study helps identify patients at high risk of early progression after CAR T who may benefit from specific interventions pre and post CAR T to improve outcomes.

Effectiveness of extracorporeal shock wave lithotripsy in urolithiasis patients under 2 years of age.

OBJECTIVE: In this study, we present our extracorporeal shock wave lithotripsy (ESWL) outcomes in urolithiasis patients under the age of two. MATERIALS AND METHODS: The procedure was performed with patients < 2 years of age sedated, under anesthesia using ketamine and Dormicum (midazolam), in the supine position. Fragmentation was evaluated by fluoroscopy after the procedure. RESULTS: A total of 74 procedures were performed on 65 kidneys. One patient with bilateral stones had two sessions of ESWL on the right side; three sessions of ESWL were performed in one patient with a unilateral stone, and two sessions were performed in seven patients with unilateral stones. All other patients underwent one session of ESWL. As post-procedural complications, hematuria was observed in 14 patients (12 mild and 2 significant), and vomiting occurred in 1 patient. Ureterorenoscopy was performed in 5 patients, and percutaneous nephrolithotomy in 6 patients due to a failed procedure. CONCLUSION: As a result, ESWL treatment is effective and has advantages such as a short hospitalization time, good reproducibility, cost-effectiveness, and a low rate of complications. Therefore, we recommend ESWL as the first-line treatment for renal and proximal ureteral stones in infants < 2 years of age.

OBIETIVO: En este estudio, presentamos nuestros resultados de ESWL en pacientes con urolitiasis menores de dos años. MATERIALES Y MÉTODOS: El procedimiento se realizó con pacientes menores de dos años sedados, bajo anestesia con ketamina y Dormicum (midazolam), en posición supina. La fragmentación se evaluó mediante fluoroscopia después del procedimiento. RESULTADOS: Se realizaron total de 74 procedimientos en 65 riñones. Un paciente con cálculos bilaterales tuvo dos sesiones de ESWL en el lado derecho; se realizaron tres sesiones de LEOC en un paciente con litiasis unilateral y dos sesiones en siete pacientes con litiasis unilateral. Todos los demás pacientes se sometieron a una sesión de ESWL. Como complicaciones post-procedimiento se observó hematuria en 14 pacientes (12 leves y 2 significativas) y vómitos en 1 paciente. Se realizó URS en 5 pacientes y NLP en 6 pacientes debido a un procedimiento fallido. CONCLUSIONES: Como resultado, el tratamiento de la ESWL es efectivo y tiene ventajas como un tiempo de hospitalización corto, buena reproducibilidad, costo-efectividad y baja tasa de complicaciones. Por tanto, recomendamos la ESWL como tratamiento de primera línea para cálculos renales y ureterales proximales en bebés < 2 años de edad.

Predestinative role acidic cerebrospinal fluid on the destiny of central channel in spinal cord following subarachnoid hemorrhage: an experimental study.

OBJECTIVE: Acidosis is the most dangerous complication in subarachnoid hemorrhage (SAH). This study aimed to investigate the effect of acidic cerebrospinal fluid on central canal structures after SAH. MATERIALS AND METHODS: Twenty-eight hybrid rabbits were studied. Blood and cerebrospinal fluid pH values were recorded before/during/after the experimental procedures. The structures related to the central canals at the level of C5 of the cervical spinal cord were then examined histopathologically. The relationship between pH values of ependymal cells and degenerated epithelial cell densities was statistically analyzed. RESULTS: Mean blood pH values and degenerated ependymal cell density (n/mm2) were as follows: 7.351 ± 0.033/23 ± 7 in control, 7.322 ± 0.059/78 ± 13 in SHAM, and 7.261 ± 0.048/254 ± 62 in study animals. Gross examinations revealed swelling, edema, pia-arachnoid adhesions, ventral canal dilatation, arachnoiditis, central canal hemorrhage, occlusions, and dilatation in the spinal cord. CONCLUSION: Cerebrospinal fluid acidosis-induced central channel pathologies should be considered an important complication of SAH following SAH.

OBJETIVO: La acidosis es la complicación más peligrosa en la hemorragia subaracnoidea (HSA). El objetivo de este estudio fue investigar el efecto del líquido cefalorraquídeo ácido en las estructuras del canal central tras la HSA. MATERIALES Y MÉTODOS: Se estudiaron 28 conejos híbridos. Se registraron los valores de pH de la sangre y del líquido cefalorraquídeo antes, durante y después de los procedimientos experimentales. A continuación se examinaron histopatológicamente las estructuras relacionadas con los canales centrales a nivel de C5 de la médula espinal cervical. Se analizó estadísticamente la relación entre los valores de pH de las células ependimarias y las densidades de células epiteliales degeneradas. RESULTADOS: Los valores medios de pH en sangre y la densidad de células ependimarias degeneradas (n/mm2) fueron los siguientes: 7.351 ± 0.033/23 ± 7 en el control, 7.322 ± 0.059/78 ± 13 en el SHAM, 7.261 ± 0.048/254 ± 62 en los animales del estudio. Los exámenes macroscópicos revelaron hinchazón, edema, adherencias pia-aracnoideas, dilatación del canal ventral, aracnoiditis, hemorragia del canal central, oclusiones y dilatación en la médula espinal. CONCLUSIONES: Las patologías del canal central inducidas por la acidosis del líquido cefalorraquídeo deben considerarse como una complicación importante de la HSA tras una hemorragia subaracnoidea.

Surgical Explantation of Impella 5.5 With Inflow Thrombus in Patients Undergoing Durable Left Ventricular Assist Device Implantation.

The Impella 5.5® (Abiomed, Danvers, MA, USA) is a microaxial flow pump that promotes left ventricular unloading and improves end-organ perfusion before durable left ventricular assist device (LVAD) implantation. Thrombus formation after Impella 5.5 insertion can occur and represents a significant challenge to device explantation. Durable LVAD implantation is typically performed without aortic cross-clamping, so a dislodged thrombus can potentially embolize and lead to catastrophic events. We describe our technique to safely explant an Impella 5.5 in patients who develop a thrombus on the inflow portion of the device before surgical LVAD implantation.

[A rare cause of intestinal obstruction: sock ingestion]. / Una causa rara de obstrucción intestinal: ingestión de calcetines.

Although most foreign bodies leave the gastrointestinal tract spontaneously without causing serious injuries such as bleeding and obstruction, they can sometimes occlude the intestine and may present with symptoms of ileus. A 14-year-old boy with cerebral palsy was admitted to our center due to persistent bilious vomiting. A foreign body (sock) was seen in the jejunal loops at laparotomy. Enterotomy and enterostomy were performed.

Aunque la mayoría de los cuerpos extraños abandonan el tracto gastrointestinal de forma espontánea sin causar lesiones graves como sangrado y obstrucción, a veces pueden ocluir el intestino y pueden presentarse con síntomas de íleo. Un niño de 14 años con parálisis cerebral ingresó en nuestro centro por vómitos biliosos persistentes. Se observó un cuerpo extraño (calcetín) en las asas yeyunales en la laparotomía. Se realizó enterotomía y enterostomía.

The association of polypoid growth pattern with lymph node involvement in endometrioid type endometrial adenocarcinoma.

Background: Tumor size is an independent predictor of lymph node metastasis and survival in the endometrioid type endometrial adenocarcinoma (EC). However, some of the ECs tend to grow towards the cavity in the polypoid pattern, which can reach very large sizes. In this study, we aimed to analyze the association of growing in the polypoid pattern of the tumor with the proportion of lymph node metastasis and extrauterine tumor spread. Methods: Four hundred seven patients were analyzed retrospectively. The effect of tumor size, tumor growing pattern, myometrial invasion, grade, and lymphovascular space invasion on the lymph node metastasis and extrauterine tumor spread were investigated. Statistical analysis consisted of unpaired t-tests for parametric data and Mann Whitney-U test for non-parametric data, whereas the Chi-square test for categorical variables. Logistic Regression, Cox Regression and multivariate analysis were used to estimate the risk predictors. Results: No association was found between the growing in polypoid pattern and lymph node metastasis (P > 0.05). In the analysis of endometrioid type EC patients who had myometrial invasion less than ½ as a subgroup, no association was found between the growing pattern and lymph node metastasis and extrauterine disease. Tumor size was found to be a statistically significant predictor of lymph node metastasis and extrauterine disease (P < 0.05). Conclusions: Lymphovascular space invasion, grade, and myometrial invasion are associated with a higher proportion of lymph node metastasis. The polypoid growth pattern of the tumor does not correlate with any histopathological parameters.

Imaging Biomarkers to Predict Outcomes in Patients With Large B-Cell Lymphoma With a Day 28 Partial Response by 18F-FDG PET/CT Imaging Following CAR-T Therapy.

BACKGROUND: CD19 directed CAR-T therapy for Large B-cell lymphoma (LBCL) has shown great therapeutic response in patients with relapsed/refractory disease with response rates of 60-80%. However, in patients with a partial response (PR) on initial day 28 post CAR-T therapy imaging, clinical uncertainty remains as half of these patients will ultimately have relapsed disease.   PATIENTS: In 24 patients receiving CD19 directed CAR-T therapy for relapsed/refractory LBCL achieving a PR on day 28, we utilize imaging biomarkers by 18F-FDG PET/CT imaging at pre CAR-T therapy baseline and day 28 to determine factors that may predict best overall response (B-OR), progression free survival (PFS), and overall survival (OS).   METHODS: Out of 75 patients receiving CAR-T therapy at a single institution, we retrospectively identified and reviewed 25 (33%) as achieving a PR on day 28. PR was defined using the 2014 Lugano classification system. All patients received standard of care CD19 directed CAR-T therapy with axicabtagene ciloleucel. Two independent nuclear medicine physicians measured baseline (pre-CAR-T therapy) and day 28 PET/CT SUVmax, SUVmean and TMV (cm3) of each lesion (node, organ or marrow uptake, if any) using ROVER software. All statistical tests were two-sided and conducted at the 0.05 level of significance. R version 1.3.1099 (R-studio) was used for statistical modeling.   CONCLUSION: We demonstrate that a higher day 28 SUVmax was significantly higher in those with a B-OR of PR and in our modeling, a lower day 28 SUVmax may predict favorable PFS and OS. Additionally, lower TMV, both at baseline and day 28, may also be predictive of longer PFS and OS, while lower TLG at baseline, but not day 28 is significantly associated with a B-OR of CR. While further study is warranted, these imaging biomarkers may allow for early identification of those with a day 28 PR at highest risk for relapse leading to early intervention to improve long term outcomes.