Median Follow-up Time For Patients Research Articles

Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn's disease: The HEAL study from GETECCU

The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

Analysis of 41 cases of non-metastatic Ewing's sarcoma in children

To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.

Correlation Analysis of Peripheral Blood B Cell Count with Clinical Features and Prognosis in Patients Newly Diagnosed with Diffuse Large B-Cell Lymphoma

To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The relationship of peripheral blood B cell count with clinical features, laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed. Patients were divided into low B-cell count group (B cell＜0.1×109/L, n=34) and high B-cell count group (B cell≥0.1×109/L, n=33) according to the median B cell count values. Compared with the high B cell count group, the low B cell count group had a higher proportion of patients with Lugano stage III-IV, elevated LDH, elevated β2-MG and IPI score 3-5 and increased CRP (P =0.033, 0.000, 0.023, 0.001, 0.033). The peripheral CD3+ and CD4+ cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group (P =0.010, 0.017). After initial treatment, overall response rate (ORR) and complete remission (CR) rate in high B cell count group were significantly higher than those in low B cell count group (P =0.032, 0.013). The median follow-up time of patients was 23(2-77) months, progression-free survival (PFS) and overall survival (OS) of patients in the high B cell count group were significantly better than those in the low B cell count group (P =0.001, 0.002). Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS (HR=4.108, P =0.002; HR=8.218, P =0.006). Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS (HR=3.116, P =0.037). Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy, which is associated with poor clinical prognosis.

Combination of BeGraft and Solaris Stent Grafts for the Covered Endovascular Reconstruction of Aortic Bifurcation-BS-CERAB Technique.

Background: This study examines the impact of the use of the combination of BeGraft and Solaris stent grafts on the outcomes during the covered endovascular reconstruction of aortic bifurcation (BS-CERAB) technique and extension to the iliac arteries. Methods: Consecutive patients with aortoiliac occlusive disease who underwent endovascular treatment using BS-CERAB between January 2020 and December 2023 were included. Patient demographics, symptoms, lesion characteristics, and procedural and follow-up details were collected and analyzed. Perioperative complications and reinterventions were also identified. Results: A total of 42 patients met the inclusion criteria (32 men, 76.2%, median age 72 years, range 59-85). Indications for treatment were intermittent claudication (42.9%) and critical limb ischemia (57.1%). Procedure success was achieved in all cases. The median patient follow-up time was 14 months (1-36). One patient died at a 10-month follow-up due to lung cancer. The mean pre-operative ABI increased from 0.37 ± 0.19 before intervention to 0.71 ± 1.23 post-operatively at 12 months (p = 0.037). The estimated primary patency rates at 3, 6, and 12 months were 90.5%, 85.7%, and 81.0% and primary assisted patency rates were 90.5%, 90.5%, and 85.7%, respectively. Secondary patency was 95.2% at 3 and 6 months and 90.5% at a 12-month follow-up. Active cancer (p = 0.023, OR 2.12 95%CI 1.14-3.25) was a risk factor for restenosis. Conclusions: This mid-term experience shows that the CERAB technique using the combination of BeGraft and Solaris stents grafts, for the endovascular treatment of severe aortoiliac atherosclerotic disease, may allow an effective reconstruction of the aortic bifurcation and iliac arteries related to high-patency and lower-reintervention rates.

Efficacy and Safety Analysis of Carfilzomib-Containing Regimen in the Treatment of Multiple Myeloma：a Multicenter Real-World Study

Purpose To investigate the efficacy and safety of carfilzomib-containing regimens in the treatment of multiple myeloma（MM） in different lines of treatment. method The clinical data of 55 multiple myeloma patients who received carfilzomib treatment in 10 medical centers in Shandong from January 2022 to March 2023 were retrospectively analyzed , and grouped according to the number of MM treatment lines, they were divided into group A : newly diagnosed multiple myeloma ( NDMM ), group B : patients with first relapse, and group C : patients treated with carfilzomib in the third line or above. Del ( 17p ), t ( 4;14 ), t ( 14;16 ) were defined as high-risk cytogenetic abnormalities result All patients with multiple myeloma were treated with the combined regimen based on carfilzomib, including 24 patients in group A , 9 patients in group B , and 22 patients in group C. Among all patients, there were 27 cases ( 49.1% ) of high-risk cytogenetics, and 13 cases with ECOG score ≥ 3 points ( 23.6% ), 10 cases ( 18.2 ) had eGFR &amp;lt;30 ml/min. The median follow-up time of patients in group A , group B and group C was 8 months, 9 months and 8 months. The overall response rate ( ORR ) was 91.7% , 88.9% and 77.3% for patients in Arms A , B and C who started carfilzomib, respectively . The ≥very good partial response ( VGPR ) rates were 75% and 66.7% for Arm A and B patients , respectively , while the ≥VGPR rate for Arm C patients was 41.0% . The negative rate of minimal residual disease ( MRD , sensitivity: 10 -6 ) in group A was 62.5% ( 15/24 ). Follow - up deadline is March 2023 On the 31st , the median progression-free survival ( PFS ) time and median overall survival ( OS ) time of patients in the three groups were not reached. After the application of carfilzomib, the incidence rate of grade 3-4 adverse events ( AE ) was 32.7% ( 18/55 ). The main hematological adverse reactions were anemia, thrombocytopenia, lymphopenia and neutropenia. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections. in conclusion Carfilzomib-based regimens in the treatment of multiple myeloma have good curative effect and safety, and the first-line and first-time relapse patients have better curative effect.

Cutaneous T-Cell Lymphoma and Dupilumab Use: A Retrospective Matched Cohort Study of Clinical Characteristics and Treatment Outcomes

Introduction: Dupilumab is a human monoclonal antibody that inhibits signaling of IL-4 and IL-13 and is currently approved by the Food and Drug Administration for the treatment of atopic dermatitis (AD). While causality has not been established, sporadic reports have emerged associating dupilumab use with the onset, progression, or subsequent diagnosis of cutaneous T-cell lymphomas, in particular mycoses fungoides (MF). The natural history of MF diagnosed after dupilumab exposure remains unclear. We performed a retrospective matched cohort study to compare the clinical characteristics and treatment outcomes of patients with MF based on prior dupilumab exposure. Methods: Through the Memorial Sloan Kettering (MSK) Research &amp; Technology data delivery platform (DataLine), we conducted a search for any patient seen by a provider in the MSK Cutaneous Lymphoma Clinic whose electronic record contained the word ‘dupilumab’ or ‘Dupixent.‘ Once the initial query was performed, we individually reviewed each patient to confirm: (1) A histologically-confirmed diagnosis of MF by an MSK dermatopathologist, and (2) Use of dupilumab prior to the histological diagnosis of MF. After identifying a cohort of patients with confirmed MF after dupilumab use (cases), we identified a matched cohort of patients with confirmed MF and no prior dupilumab use (controls). Specifically, we matched patients for stage at diagnosis, date of birth and age at diagnosis (+/- 5 years), and date of presentation (+/- 5 years). Clinical data and treatment outcomes were collected by clinical review. Baseline characteristics were summarized using descriptive statistics and compared between the two groups using the Wilcoxon rank sum test, Pearson's Chi-squared test, and Fisher's exact test. Overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were estimated as the elapsed time from initial diagnosis to death, disease recurrence, and progression, respectively. Kaplan-Meier estimates were stratified by exposure to dupilumab, and differences between the estimates were compared using the log-rank test. Results: We identified 25 patients who presented with a new, histologically-confirmed diagnosis of MF following dupilumab treatment for a diagnosis of AD. In 16 of these patients, AD was diagnosed based on a skin biopsy, whereas in 9 patients the diagnosis was based on clinical features only. Among 16 patients with known duration of dupilumab use, the median duration of use was 5.0 months (min/max: 1.5-24 months). In total, 14 patients were diagnosed with early-stage disease (IA n=2, IB n=12) and 11 were diagnosed with advanced stage disease (IIB n=4, IIIA n=2, IVA1 n=5). The estimated time from dupilumab treatment to lymphoma diagnosis was 10.2 months, and the median age at lymphoma diagnosis was 53 years (min/max: 28-84). Compared to the cohort of 25 matched patients with MF and no prior dupilumab use ( Table 1), no difference was observed in race, sex, initial therapy (skin-directed vs. systemic), or total number of therapies. The median follow-up time for patients exposed to dupilumab was 13.2 months (95% CI: 6.8-21.9), and 20.7 months (95% CI: 13.4-27.8) for those not exposed. No differences were observed in OS, PFS, or RFS between the exposed (dupilumab) and non-exposed (non-dupilumab) cohorts ( Figure 1). Two-year OS, PFS, and RFS in the non-dupilumab cohort was 85.0%, 47.3%, and 70.7%, compared to 100.0%, 41.5%, and 79.6% in the dupilumab cohort. One patient in the dupilumab-exposed cohort died of a non-lymphoma malignancy, whereas 4 patients in the non-exposed cohort died (3 due to lymphoma, 1 due to unknown causes). Conclusions: In summary, we identified a relatively large cohort of patients with MF diagnosed after dupilumab treatment. Patients presented with early and advanced-stage disease. Outcome were comparable to a matched cohort of non-exposed patients with MF. The causal relationship between dupilumab and MF remains unproven and deserves dedicated biological study.

Long-Term Follow-up of Humanized and Murine CD19 CAR-T Cell Therapy for B-Cell Malignancies

Aim: CD19 chimeric antigen receptor T cell (CAR-T) therapy is a revolutionary treatment for relapsed/refractory (R/R) B-cell hematologic malignancies. However, the safety and efficacy of murine CAR-T cells which have been widely used as commercialized products still need to be improved. Similarly, murine CAR-T encountered the problem that CAR-related immunogenicity existed after the infusion, which led to the failure of the re-infusion of CAR-T cells. As an improved generation of murine CAR-T cells, whether humanized CAR-T therapy can overcome the above shortcomings remains to be explored. Methods: In this study, the differences in safety, efficacy, and long-term follow-up results of murine and humanized CD19 CAR-T cells in patients with B-cell malignancies were collected and analyzed. A total of 130 patients were enrolled, including 35 patients with murine CAR-T and 95 with humanized CAR-T cells (NCT 02965092, NCT 04008251). Results： The proportion of patients with cytokine release syndrome (CRS) in the murine and humanized groups was 54.3%（19/35） and 61.1%（58/95）, respectively. A significantly higher proportion of patients suffered from severe CRS in the murine group than that in the humanized CAR-T group (17.14% vs. 7.4%, P=0.0233), and one patient in each group died of Grade 5 CRS. The incidence of grade 1-2 Immune effector cell-associated neurotoxicity syndrome (ICANS) was 11.4% (murine: 4/35) and 5.3% (humanized: 5/95), but high-grade ICANS was not observed. Among patients receiving murine CAR-T cells, 80% achieved objective response (OR), 71.43% achieved complete response (CR) and the CR rate of patients with leukemia was 74.19%. The OR rate and CR rate of patients in the humanized group were 75.79% and 63.16%, respectively, while the CR rate of patients with leukemia receiving humanized CAR-T cells was 89.58%. The median follow-up time of patients in the murine and humanized groups was 7 months (0.6-75 months) and 5.5 months (0.5-34 months), respectively. The median progression-free survival (PFS) of patients with murine CAR-T cells was 11 months and that of patients with humanized CAR-T products was 12 months. Both of the median overall survival (OS) were not reached. Among the 48 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a higher OS rate (84.64% vs. 59.26%, P=0.1479) and a significantly improved PFS (43.94% vs. 33.33%, P=0.0217, Figure 1). Bridging transplantation was an independent factor in prolonging OS (x 2=8.017, p=0.0046) and PFS (x 2=6.584, p=0.0103) of patients with leukemia. Neither species of chimeric antigen receptor nor common risk factors such as age, recurrence, bone marrow burden, BCR-ABL fusion gene had significant effect on patients' long-term follow-up outcomes (Table 1). Four patients received CAR-T therapies more than once. Three of them still achieved varying degrees of long-term remission after multiple humanized CAR-T infusions. However, one patient relapsed as soon as one month after his second infusion of murine CAR-T cells. Conclusion: Results indicate that humanized CAR-T therapy showed better safety and durable efficacy, especially in patients with higher tumor burden in bone marrow. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients' failures of CAR-T therapies.

Use of uterine manipulator and uterine perforation in minimally invasive endometrial cancer surgery.

Safety of the uterine manipulator (UM) within endometrial cancer (EC) surgery is being questioned. Its use might be one of the issues for potential tumor dissemination during the procedure, especially in the case of uterine perforation (UP). No prospective data on this surgical complication, nor on the oncological consequences exist. The aim of this study was to assess the rate of UP while using UM when performing surgery for EC and the impact of UP on the choice of adjuvant treatment. We conducted a prospective single-center cohort study from November 2018 to February 2022, considering all EC cases surgically treated by a minimally invasive approach with the help of a UM. Demographic, preoperative, postoperative and adjuvant treatment corresponding to the included patients were collected and comparatively analyzed according to the absence or presence of a UP. Of the 82 patients included in the study, 9 UPs (11%) occurred during surgery. There was no significant difference in demographics and disease characteristics at diagnosis that may have induced UP. The type of UM used or the approach (laparoscopic vs. robotic) did not influence the occurrence of UP (p=0.44). No positive peritoneal cytology was found post hysterectomy. There was a statistically significantly higher rate of lymph-vascular space invasion within the perforation group, 67% vs. 25% in the no perforation group, p=0.02. Two out of nine (22%) adjuvant therapies were changed because of UP. The median follow-up time for patients was 7.6 months (range 0.5-33.1 months). No recurrence was found in the UP group. Our study found a uterine perforation rate of 11%. This information needs to be further integrated to consider the usefulness of MU for EC surgery.

Efficacy and safety analysis of immune checkpoint inhibitors plus angiogenesis inhibitors for treatment of advanced driver-negative NSCLC in elderly patients: A retrospective study.

e21044 Background: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic drugs may have synergistic effects in elderly patients with advanced driver-gene wild-type non-small cell lung cancer (NSCLC), but its true efficacy remains unclear. In addition, the chemotherapy tolerance of elderly NSCLC patients is poor, and the precise identification of the population who can benefit from ICIs combined with angiogenesis inhibitors is also the focus of current research. Methods: We retrospectively compared the clinical efficacy and safety of ICIs combined with or without antiangiogenic agents in elderly patients with advanced driver-gene negative NSCLC who were ≥65 years old in the Cancer Center of the Affiliated Suzhou Hospital of Nanjing Medical University. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs). Results: A total of 36 patients in the IA group（Immune checkpoint inhibitors plus angiogenesis inhibitors group) and 43 patients in the NIA group（Immune checkpoint inhibitors without angiogenesis inhibitors group) were enrolled in the study between January 1, 2019 and December 31, 2021. The median follow-up time for patients in IA group and NIA group was 18.2 months (95%CI: 14 - 22.5 months) and 21.4 months (95%CI: 16.7 -26.1 months), respectively. The median PFS and median OS were longer in the IA group compared to the NIA group（8.1 months vs 5.3 months；HR for PFS: 0.778, 95%CI: 0.474-1.276, P = 0.32; NA vs 30.9 months; HR for OS: 0.795, 95%CI: 0.396-1.595, P = 0.519). Subgroup analysis showed that patients in the IA group had significantly longer PFS in the subgroup with PD-L1 expression ≥50% (P = 0.017), and the relationship between treatment regimens and outcomes was still discrepant in different PD-L1 expression levels (P for interaction = 0.002). There was no significant difference in ORR between the two groups (23.3% vs 30.5%, P = 0.465). The incidence of adverse events in IA group was lower than that in NIA group (39.5% vs 19.4%, P = 0.05), and the cumulative incidence of treatment interruptions due to adverse events was significantly reduced (P = 0.045). Conclusions: In elderly patients with advanced driver-gene wild-type NSCLC, the addition of antiangiogenic agents to ICIs therapy did not provide significant clinical benefit, but the incidence of treatment interruptions due to adverse events was significantly reduced. In the subgroup analysis, we found that the clinical benefit of this combination therapy was observed in patients with PD-L1 expression ≥50%, which warrants further exploration. Clinical trial information: NCT05688046 .

Pulsed-field- vs. cryo- vs. radiofrequency ablation: one-year recurrence rates after pulmonary vein isolation in patients with paroxysmal atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background A multipolar pulsed-field ablation (PFA) catheter has recently been introduced and showed favorable data in terms of safety and procedural efficiency of pulmonary vein isolation (PVI) for atrial fibrillation (AF). Long-term outcome data in comparison to other ablation modalities however is lacking. Purpose To compare procedural and one-year recurrence data of patients with paroxysmal AF (paroxAF) undergoing a first PVI using PFA, cryoballoon ablation (Cryo), or radiofrequency (RFA). Methods Consecutive patients with paroxAF undergoing a first PVI with PFA at our institution from May to December 2021 were included. For comparison, patients with paroxAF undergoing a first PVI with Cryo or RFA between May 2020 and March 2021 were included. A 3-D electro-anatomical mapping system was used in PFA and RFA, but not in Cryo. The following ablation protocols were used to achieve acute PVI: In the PFA group, the standard 32-applications lesion-set and supplementary applications at the discretion of the operator. In the Cryo group, a time-to-effect plus two minutes strategy and in the RFA group following to the CLOSE protocol. Patients were followed with 7d-Holter ECGs 3, 6, and 12 months after ablation. The primary endpoint was recurrence of any atrial arrhythmias following a blanking period of 3 months. Results A total of 202 patients were included (PFA: 32; Cryo: 82; RF: 88). Age, gender, CHA2DS2-VASc score, LVEF and LAVI did not differ among the groups (Table). Median procedure times were shortest with Cryo (76 [interquartile range 60-95] min) followed by PFA (94 [82-110] min) and RFA (157 [126-211] min, p &amp;lt; 0.01). Fluoroscopy dose was lowest with RFA (1.4 [0.6-2.5] Gycm2) followed by PFA (4.8 [3.5-7.9] Gycm2) and Cryo (5.3 [2.8-10.2] Gycm2, p &amp;lt; 0.01). Median follow-up time in patients without recurrence was 12 [10-12] months for the PFA group, 12 [12-13] months for the Cryo group and 13 [12-13] months for the RFA group. There was a trend towards fewer recurrences of atrial arrhythmias with PFA compared to Cryo and RFA (PFA 7%, Cryo: 25%, RFA: 20%, p = 0.13, Figure). Conclusion Recurrences of atrial arrhythmias 12 months after PFA PVI for paroxAF may be lower compared to Cryo and RFA. Larger prospective randomized studies are needed to confirm this initial experience.

Pulsed-field- vs. cryo- vs. radiofrequency ablation: one-year recurrence rates after pulmonary vein isolation in patients with persistent atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background A multipolar pulsed-field ablation (PFA) catheter has recently been introduced and showed favorable data in terms of safety and procedural efficiency of pulmonary vein isolation (PVI) for atrial fibrillation (AF). Long-term outcome data in comparison to other ablation modalities however is lacking. Purpose To compare procedural and one-year recurrence data of patients with persistent AF (persAF) undergoing a first PVI using PFA, cryoballoon ablation (Cryo), or radiofrequency (RFA). Methods Consecutive patients with persAF undergoing a first PVI with PFA at our institution from May to December 2021 were included. For comparison, patients with persAF undergoing a first PVI with Cryo or RFA between May 2020 and March 2021 were included. A 3-D electro-anatomical mapping system was used in PFA and RFA, but not in Cryo. The following ablation protocols were used to achieve acute PVI: In the PFA group, the standard 32-applications lesion-set and supplementary applications at the discretion of the operator. In the Cryo group, a time-to-effect plus two minutes strategy and in the RFA group following to the CLOSE protocol. Patients were followed with 7d-Holter ECGs 3, 6, and 12 months after ablation. The primary endpoint was recurrence of any atrial arrhythmia following a blanking period of 3 months. Results A total of 177 patients were included (PFA: 65; Cryo: 63; RF: 49). Age, gender, CHA2DS2-VASc score, LVEF and LAVI did not differ among the groups (Table). Median procedure time was different among the groups (PFA: 109 [interquartile range 88-130] min, Cryo: 81 [62-96] min, RF: 177 [153-200] min, p &amp;lt; 0.01). Fluoroscopy dose was different among groups: RF (1.9 [0.7-4.9] Gycm2), PFA (8.3 [4.3-19.0] Gycm2), and Cryo (9.5 [4.8-19.1] Gycm2, p&amp;lt;0.01). Median follow-up time in patients without recurrence was 13 [11-13] months for the PFA group, 13 [12-13] months for the Cryo group and 12 [11-13] months for RFA group. Recurrence of atrial arrhythmias in the KM-analysis after 12 months was not different in all three groups (PFA 44%, Cryo: 33%, RFA: 51%, Figure). Conclusion In patients with persAF, recurrence of atrial arrhythmias 12 months after PFA-PVI only is high, regardless of ablation modality. Assessment of strategies including ablation of extra-PV targets in some patients with persAF is needed.

Characteristics of Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis Without Therapeutic Immune Suppression

Progressive multifocal leukoencephalopathy can occur in the context of systemic sarcoidosis (S-PML) in the absence of therapeutic immune suppression and can initially be mistaken for neurosarcoidosis or other complications of sarcoidosis. Earlier recognition of S-PML could lead to more effective treatment of the disease. To describe characteristics of patients with S-PML. For this case series, records from 8 academic medical centers in the United States were reviewed from 2004 to 2022. A systematic review of literature from 1955 to 2022 yielded data for additional patients. Included were patients with S-PML who were not receiving therapeutic immune suppression. The median follow-up time for patients who survived the acute range of illness was 19 months (range, 2-99). Data were analyzed in February 2023. Sarcoidosis without active therapeutic immune suppression. Clinical, laboratory, and radiographic features of patients with S-PML. Twenty-one patients with S-PML not receiving therapeutic immune suppression were included in this study, and data for 37 patients were collected from literature review. The median age of the 21 study patients was 56 years (range, 33-72), 4 patients (19%) were female, and 17 (81%) were male. The median age of the literature review patients was 49 years (range, 21-74); 12 of 34 patients (33%) with reported sex were female, and 22 (67%) were male. Nine of 21 study patients (43%) and 18 of 31 literature review patients (58%) had simultaneous presentation of systemic sarcoidosis and PML. Six of 14 study patients (43%) and 11 of 19 literature review patients (58%) had a CD4+ T-cell count greater than 200/μL. In 2 study patients, a systemic flare of sarcoidosis closely preceded S-PML development. Ten of 17 study patients (59%) and 21 of 35 literature review patients (60%) died during the acute phase of illness. No meaningful predictive differences were found between patients who survived S-PML and those who did not. In this case series, patients with sarcoidosis developed PML in the absence of therapeutic immune suppression, and peripheral blood proxies of immune function were often only mildly abnormal. Systemic sarcoidosis flares may rarely herald the onset of S-PML. Clinicians should consider PML in any patient with sarcoidosis and new white matter lesions on brain magnetic resonance imaging.

MP41-02 TUMOR SIZE IS ASSOCIATED WITH GROWTH KINETICS IN SMALL RENAL MASSES ON ACTIVE SURVEILLANCE

You have accessJournal of UrologyCME1 Apr 2023MP41-02 TUMOR SIZE IS ASSOCIATED WITH GROWTH KINETICS IN SMALL RENAL MASSES ON ACTIVE SURVEILLANCE Maximilian Pallauf, Michael Rezaee, Roy Elias, Tina Wlajnitz, Sean A. Fletcher, Khalid Alkhatib, Peter Chang, Andrew A. Wagner, James M. McKiernan, Mohammad E. Allaf, Phillip M. Pierorazio, and Nirmish Singla Maximilian PallaufMaximilian Pallauf More articles by this author , Michael RezaeeMichael Rezaee More articles by this author , Roy EliasRoy Elias More articles by this author , Tina WlajnitzTina Wlajnitz More articles by this author , Sean A. FletcherSean A. Fletcher More articles by this author , Khalid AlkhatibKhalid Alkhatib More articles by this author , Peter ChangPeter Chang More articles by this author , Andrew A. WagnerAndrew A. Wagner More articles by this author , James M. McKiernanJames M. McKiernan More articles by this author , Mohammad E. AllafMohammad E. Allaf More articles by this author , Phillip M. PierorazioPhillip M. Pierorazio More articles by this author , and Nirmish SinglaNirmish Singla More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) is an accepted treatment strategy for small renal masses (SRM) <4 cm. Intervention is recommended for SRMs exceeding growth rates (GR) of 0.5 cm/year. We sought to identify clinical factors predictive of GR >0.5 cm/year for SRM on AS. METHODS: We queried the prospective, multi-institutional Delayed Intervention and Surveillance for SRM (DISSRM) registry for patients enrolled in AS. We tabulated clinical factors, including age, sex, and tumor size, and quantified GRs of SRMs between study enrollment and delayed intervention, metastasis, death, or last follow-up, whichever occurred first. GR was defined by the change in tumor size over time between the first and latest imaging. We defined growth progression as a GR in excess of 0.5 cm/year. We used recurrent-event multivariable Cox-regression modeling to test the associations between clinical factors and growth progression; age and tumor size were handled as time-varying covariates. Tumor size was tested as a continuous and dichotomized variable based on a cutoff of 2 cm, endorsed by the AUA guidelines. To account for GR variability within the first few months of AS, we excluded follow-up visits earlier than six months. RESULTS: Between 2009 and 2022, 591 patients were initially enrolled onto AS within the DISSRM registry, of whom 332 were on AS for at least six months. The median follow-up time of patients who continued AS was 4.0 years (IQR 2.6-6.1). Sixty-six patients (20%) exhibited growth progression, but no patient developed metastatic disease. Fifty patients (15%) underwent delayed intervention. While age and sex were not associated with growth progression, tumor size was an independent predictor of growth progression on multivariable analysis (HR 2.61 (95% CI 2.16-3.15), p<0.001). On dichotomization of tumor size, we found that tumors ≥ 2 cm were significantly associated with growth progression compared to those <2 cm (HR 4.29 (95% CI 2.43-7.61), p<0.001) (Figure). The mean GR for tumors ≥ 2 cm was 0.21 cm/year (±0.31) vs. 0.06 cm/year (±0.26) for those <2 cm. CONCLUSIONS: Larger tumor size is independently associated with clinically meaningful growth progression (GR >0.5 cm/year) for SRMs on AS. Identifying clinical factors predictive of growth kinetics for SRMs is important to guide patient counseling by informing personalized strategies of AS versus intervention. Source of Funding: This publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR003098 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH.Pallauf M gratefully acknowledges the support of the Paracelsus Medical University Research and Innovation Fund (2022-FIRE-004-Pallauf). © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e554 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maximilian Pallauf More articles by this author Michael Rezaee More articles by this author Roy Elias More articles by this author Tina Wlajnitz More articles by this author Sean A. Fletcher More articles by this author Khalid Alkhatib More articles by this author Peter Chang More articles by this author Andrew A. Wagner More articles by this author James M. McKiernan More articles by this author Mohammad E. Allaf More articles by this author Phillip M. Pierorazio More articles by this author Nirmish Singla More articles by this author Expand All Advertisement PDF downloadLoading ...

A Semmelweis Egyetem Bőr-, Nemikórtani és Bőronkológiai Klinika Sézary szindróma miatt kezelt betegeivel szerzett tapasztalatok összefoglalása

Sézary syndrome is a primary cutaneous T-cell lymphoma (CTCL) with severe clinical manifestations characterized by erythroderma, lymph node and blood involvement. In our retrospective database-based study we reviewed data of 23 patients (8 women and 15 men) diagnosed and treated with Sézary syndrome at our Indtitute from 1st January 2016 to 30th June 2022. The median follow-up time of patients was 42 (6-167) months. According to the course of the disease, 17.4% of patients went into complete remission, 30.4% achieved partial remission, 13% remained stable, while progression was seen in 39.1% of the cases. The most frequently used therapeutic entities were extracorporeal photopheresis (95.6%), bexarotene (52.2%), methotrexate (43.5%) and acitretine (34.8%). The diagnosis and treatment of Sézary syndrome remains a significant challenge. In all cases of erythroderma, histological sampling is recommended, and if CTCL is confirmed, staging examinations for TNMB classification should be performed. In the early stages of the disease, access to skin-directed therapies (phototherapy, radiotherapy) and immunomodulatory systemic treatments (ECP, retinoids, MTX) is crucial, while cooperation with hematological and stem cell transplantation centers is essential in the care of patients showing progression.

Impact of an Expanded Definition of Family History on Outcomes of Active Surveillance for Prostate Cancer.

Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes. Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, and biochemical recurrence after treatment. Statistical analyses were conducted using the Kaplan-Meier method and Cox regression. Among 855 evaluable patients, 300 (35.1%) patients had any family history of prostate cancer, and 95 (11.1%) had a family history of related malignancies suggestive of a hereditary cancer syndrome. Family history of prostate cancer alone was not associated with biopsy progression, whereas family history suggestive of a hereditary cancer syndrome was associated with a significantly increased risk of biopsy progression (HR 1.43, 95%CI 1.01-2.02), independent of other known clinicopathological risk factors in multivariable analysis. Similarly, family history suggestive of a hereditary cancer syndrome was associated with significantly lower treatment-free survival (HR 1.58, 95%CI 1.14-2.18) in multivariable analysis. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. An expanded family history suggestive of a hereditary cancer syndrome is an independent predictor of biopsy progression during active surveillance. Men with such a family history may still be offered active surveillance but should be counseled regarding the higher risk of disease progression.

Role of crescents for lupus nephritis in clinical, pathological and prognosis: a single-center retrospective cohort study

BackgroundReferring to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2018 pathological classification, we aim to reveal the significance of cellular/fibrocellular crescents in lupus nephritis (LN) patients.MethodsPatients with LN proven by renal biopsy at the First Affiliated Hospital of Wenzhou Medical University from December 2001 to November 2017 were identified, and eligible cases were divided into two groups according to the presence or absence of cellular/fibrocellular crescents in renal biopsy tissues.ResultsA total of 401 LN patients were identified from our follow-up database, and 296 eligible LN patients were enrolled in the study. Of these patients, 146 patients in the group without cellular/fibrocellular crescents (non-crescent group) and 150 patients in the group with cellular/fibrocellular crescents (Crescent group). The median follow-up time of patients was 47 months, and a total of 54 patients progressed to the composite endpoint. Crescent group had higher serum creatinine, lower serum albumin, higher systemic lupus erythematosus (SLE) disease activity index, and higher activity index of renal tissue. The interaction between cellular/fibrocellular crescents and proteinuria at baseline was associated with the prognostic risk of LN (P = 0.006). In the group with proteinuria < 3.5 g/24 h, the prognosis of crescent group was significantly worse than of non-crescent group (P < 0.001), while in the group with proteinuria ≥ 3.5 g/24 h, there was no significant relationship between crescents and prognosis (p = 0.452). By multivariable Cox hazard analysis, positive anti-dsDNA, chronic index of renal biopsy tissue, cellular/fibrocellular crescents and its interaction with 24 h proteinuria were independent risk factors for poor prognosis of LN.ConclusionsLN patients with cellular/fibrocellular crescents had more severe and active disease features, and cellular/fibrocellular crescents is a risk factor for poor prognosis of LN. There was an interaction between cellular/fibrocellular crescents and proteinuria in predicting poor prognosis, and among patients with low levels of proteinuria at the time of renal biopsy, those with crescents had a worse long-term prognosis than those without crescents.

Prognostic significance of frailty status in patients with primary lung cancer

Lung cancer has one of the highest morbidity and mortality rates in the world. Frailty is common in many countries and is a major cause of premature functional decline and premature death in older adults, and may affect the treatment and prognosis of lung cancer patients. To investigate the predictive value of frailty at diagnosis on all-cause mortality in lung cancer patients, this study retrospectively collected and analysed clinical information on lung cancer patients from 2015–2018. A total of 1667 patients with primary lung cancer were finally included in this study. The median follow-up time of patients was 650 (493, 1001.5) days. A total of 297(17.8%) patients had FI-LAB(the frailty index based on laboratory test) status of frail at the moment of diagnosis and the all-cause mortality rate for all patients was 61.1% (1018/1667). In a univariate model, we found a higher total all-cause mortality risk in frail patients (frail vs. robust, HR(hazard ratio) = 1.616, 95% CI(confidence interval) = 1.349,1.936), after balancing other variables combined into model 1 to model 6. The results were analyzed visually using ROC(Receiver operating characteristic) curves with nomogram and the AUC values ranged from 0.866–0.874. The final inclusion of age, TNM stage, CCI(Charlson comorbidity index) score, surgery history and chemotherapy into a multifactorial model balanced the predictive power of frailty grading on all-cause mortality. The study showed that for lung cancer patients, the higher the level of frailty at diagnosis, the higher the risk of all-cause mortality. In the context of widespread electronic medical records in hospitals, it is convenient and feasible to use FI-LAB to assess the prognosis of lung cancer patients.

Efficacy and Safety Analysis of Immune Checkpoint Inhibitors plus Angiogenesis Inhibitors for the Treatment of Advanced Driver-negative NSCLC in Elderly Patients: A Retrospective Study.

Background and Objective: Immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors may have synergistic effects in elderly patients with advanced driver-negative NSCLC, but its true efficacy remains unclear. In addition, chemotherapy tolerance in elderly NSCLC patients is poor, and the precise identification of the population that may benefit from ICIs combined with angiogenesis inhibitors is also the focus of current research. Methods: We retrospectively compared the efficacy and safety of ICIs combined with or without antiangiogenic agents in elderly patients with advanced driver-gene negative NSCLC ≥65 years of age in the Cancer Center of Suzhou Hospital Affiliated to Nanjing Medical University. The primary endpoint was PFS. Secondary endpoints were OS, ORR, and immune-related adverse events (irAEs). Results: A total of 36 patients in the IA group (immune checkpoint inhibitors plus angiogenesis inhibitors group) and 43 patients in the NIA group (immune checkpoint inhibitors without angiogenesis inhibitors group) were enrolled in the study between January 1, 2019 and December 31, 2021. The median follow-up time for patients in the IA group and NIA group was 18.2 months (95%CI: 14 - 22.5 months) and 21.4 months (95%CI: 16.7 -26.1 months), respectively. The median PFS and median OS were longer in the IA group compared to the NIA group (8.1 months vs 5.3 months; HR for PFS: 0.778, 95%CI: 0.474-1.276, P=0.32; NA vs 30.9 months; HR for OS: 0.795, 95%CI: 0.396-1.595, P=0.519). There were no significant differences in median PFS and median OS between the two groups. Subgroup analysis showed that patients in the IA group had significantly longer PFS in the subgroup with PD-L1 expression ≥50% (P=0.017), and the association between different groups and disease progression was still different in the two subgroups (P for interaction = 0.002). There was no significant difference in ORR between the two groups (23.3% vs 30.5%, P=0.465). The incidence of irAEs in the IA group was lower than that in the NIA group (39.5% vs 19.4%, P=0.05), and the cumulative incidence of treatment interruptions due to irAEs was significantly reduced (P=0.045). Conclusion: In elderly patients with advanced driver-negative NSCLC, the addition of antiangiogenic agents to ICIs therapy did not provide significant clinical benefit, but the incidence of irAEs and treatment interruptions due to irAEs was significantly reduced. In the subgroup analysis, we found that the clinical benefit of this combination therapy was observed in patients with PD-L1 expression ≥50%, which warrants further exploration.

COVID-19 Vaccine Effectiveness Among Patients With Maintenance Dialysis; Observations From Population Level Cohort Studies in 2 Large Canadian Provinces.

It was unknown if the effectiveness of COVID-19 vaccines could vary between regions. To explore key differences in COVID-19 pandemics in British Columbia (BC) and Ontario (ON) and to investigate if the vaccine effectiveness (VE) among maintenance dialysis population could vary between these 2 provinces. Retrospective cohort. This retrospective cohort study included patients from population-level registry in BC who were on maintenance dialysis from December 14, 2020, to December 31, 2021. The COVID-19 VE among BC patients were compared to the previously published VE among similar patient population in ON. Two-sample t-test for unpaired data were used to investigate if the VE estimates from BC and ON were statistically significantly different. Exposure to COVID-19 vaccines (BNT162b2, ChAdOx1nCoV-19, mRNA-1273) was modeled in a time-dependent fashion. Reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 infection and related severe outcome defined by hospitalization or death. Time-dependent Cox regression analysis. This study using BC data included 4284 patients. Median age was 70 years and 61% was male. Median follow-up time was 382 days. 164 patients developed COVID-19 infection. The ON study by Oliver et al included 13 759 patients with a mean age of 68 years. 61% of the study sample was male. Median follow-up time for patients in the ON study was 102 days. A total of 663 patients developed COVID-19 infection. During the overlapped study periods, BC had 1 pandemic wave compared to 2 in Ontario with substantially higher infection rates. Vaccination timing and roll out among the study population were substantially different. Median time between first and second dose was 77 days (interquartile range [IQR] 66-91) in BC compared to 39 days (IQR = 28-56) in Ontario. Distribution of COVID-19 variants during the study period appeared to be similar. In BC, compared to pre-vaccination person-time, risk of developing COVID-19 infection was 64% (aHR [95% CI] 0.36 [0.21, 0.63]), 80% (0.20 [0.12, 0.35]) and 87% (0.13 [0.06, 0.29]) less when exposed to 1 dose, 2 doses, and 3 doses, respectively. In contrast, risk reduction among Ontario patients was 41% (0.59 [0.46, 0.76]) and 69% (0.31 [0.22, 0.42]) for 1 dose and 2 doses, respectively (patients did not receive the third dose by study end date of June 30, 2021). VE against COVID-19 infection in BC and ON was not statistically significantly different, the P values for exposure to 1 dose and 2 doses comparisons were 0.103 and 0.163, respectively. Similarly, in BC, risk of developing COVID-19-related hospitalization or death were 54% (0.46 [0.24, 0.90]), 75% (0.25 [0.13, 0.48]) and 86% (0.14 [0.06, 0.34]) less for 1 dose, 2 doses, and 3 doses, respectively. Interestingly, exposure to second dose appeared to provide better protection against severe outcomes in Ontario versus BC, risk reduction was 83% (aHR = 0.17, 95% CI [0.10, 0.30]) and 75% (aHR = 0.25, 95% CI [0.13, 0.48]), respectively. However, the adjusted hazard ratios were not statistically significantly different between BC and ON, the P values were 0.676 and 0.369 for exposure to 1 dose and 2 doses, respectively. Infection rate, variant distribution, and vaccination strategies were compared using publicly available data. VE estimates were compared from 2 independent cohort studies from 2 provinces without patient-level data sharing. Health Canada approved COVID-19 vaccines were highly effective among patients with maintenance dialysis from BC and ON. Although there appeared to be between province differences in pandemic waves and vaccination strategies, the VE against COVID-19 infection as well as related severe outcome appeared to be not statistically significantly different. A nationally representative VE could be estimated using pooled data from multiple regions.

Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study.

In a continuously ageing population of patients with congenital heart disease (CHD), understanding the long-term risk of morbidity is crucial. The aim of this study was to compare the lifetime risks of developing comorbidities in patients with simple CHD and matched controls. Using the Danish nationwide registers spanning from 1977 to 2018, simple CHD cases were defined as isolated atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis, or patent ductus arteriosus in patients surviving until at least 5 years of age. There were 10 controls identified per case. Reported were absolute lifetime risks and lifetime risk differences (between patients with simple CHD and controls) of incident comorbidities stratified by groups and specific cardiovascular comorbidities. Of the included 17 157 individuals with simple CHD, the largest subgroups were ASD (37.7%) and VSD (33.9%), and 52% were females. The median follow-up time for patients with CHD was 21.2 years (interquartile range: 9.4-39.0) and for controls, 19.8 years (9.0-37.0). The lifetime risks for the investigated comorbidities were higher and appeared overall at younger ages for simple CHD compared with controls, except for neoplasms and chronic kidney disease. The lifetime risk difference among the comorbidity groups was highest for neurological disease (male: 15.2%, female: 11.3%), pulmonary disease (male: 9.1%, female: 11.7%), and among the specific comorbidities for stroke (male: 18.9%, female: 11.4%). The overall risk of stroke in patients with simple CHD was mainly driven by ASD (male: 28.9%, female: 17.5%), while the risks of myocardial infarction and heart failure were driven by VSD. The associated lifetime risks of stroke, myocardial infarction, and heart failure in both sexes were smaller in invasively treated patients compared with untreated patients with simple CHD. Patients with simple CHD had increased lifetime risks of all comorbidities compared with matched controls, except for neoplasms and chronic kidney disease. These findings highlight the need for increased attention towards early management of comorbidity risk factors.