Macapagal, Sharina

Abstract Introduction: The real-world outcomes in patients (pts) with PCALCL in the era of targeted therapies like Brentuximab Vedotin (BV) is not well defined due to lack of large multicenter studies. We conducted a multicenter retrospective analysis (RWA) to assess patient and disease characteristics, treatment patterns, survival outcomes and impact of novel therapies in this rare type of cutaneous T cell lymphoma (CTCL). Methods: The analysis included 167 adult (≥18 years) patients (pts) with PCALCL across 9 academic institutions in the United States diagnosed between 01/2012 to 06/2022. The study was approved by the Institutional Review Boards at the respective sites. Demographic and disease factors were summarized using descriptive statistics. Overall survival (OS) and relapse-free survival (RFS) were estimated using Kaplan-Meier method and compared via log rank tests. Prognostic models included factors such as age, sex, race, performance status (PS), disease stage, type of initial lesion, presence of B symptoms, previous history of lymphomatoid papulosis and prior transplant. Prognostic factors for survival were assessed using both univariable and multivariable Cox proportional hazard models. Results: The median age at diagnosis was 61 (range 18-93) years. The majority of pts were male (55%) and white (82%), with good PS as indicated by an ECOG 0-1 (71%). The initial skin presentation consisted of tumors in 62% of the pts, while 34% presented with plaques or patches. Notably, no pts presented with erythroderma. Most pts underwent PET scan for staging at initial diagnosis (83%) with the majority having early-stage (IA-IIA) disease (86%). Furthermore, palpable lymph nodes (11%) and the presence of B symptoms (4%) were rare at diagnosis, and no pts had blood involvement. The most common sites of involvement were extremities (33%) followed by the head and neck (H&N) and trunk (31% each). Immunophenotyping revealed CD4 positivity in 59% of pts and CD8 positivity in 25%. The T cell receptor (TCR) rearrangement was positive in 28% of pts, though it was not completed in the majority of cases (72%). Most common initial treatments included localized radiation (61%) and surgical excision (19%). A small subset of pts received frontline systemic chemotherapy regimens such as cytotoxic chemotherapy (11%), BV (8%) and oral methotrexate (MTX) (8%). Approximately 7% of the pts had a stem cell transplant. Overall response rate (ORR) for radiation, oral MTX, BV and cytotoxic chemotherapy were 78% (CR:78% 74/100), 42% (CR:63% 6/12) and 39% (CR:67% 6/12), 89% (CR: 88% 15/18) respectively. At a median follow-up of 3.8 years (range 0.04-10.23), the median RFS and OS were 2.7 years (95% CI:1.86, 3.43) and 12 years (95% CI:10.6- NA) respectively. The estimated 3- and 5-year RFS are 46% (95% CI:0.38, 0.55) and 37% (95% CI:0.28, 0.46) respectively. The estimated 3- and 5-year OS were 89% (95% CI:0.82, 0.93) and 82% (95% CI:0.73, 0.88) respectively. At the time of the last follow-up, 79% were alive, while 21% were deceased. The cause of death (COD) was unknown in 50% of the cases and only 10% (3/of deaths were attributed to lymphoma. Other known CODs included infection (20%) and second malignancies 7%. On univariate analysis (UVA), age (p=.007), female sex (p=.04), ECOG PS 1-2 compared to 0 (p=.007) and prior transplant (p=.009) predicted for worse RFS. On multivariate analysis (MVA), only ECOG PS 1-2 (HR 2.31, 95 CI:1.06, 1.18, p=.009) and prior transplant (HR 5.38, 95 CI:2.30, 12.57, p=.0001) had a significant impact on RFS. Age and presence of B symptoms were strong predictors of OS on both UVA (age p=<.0001; B symptoms p=<.0001) and MVA (age: HR 1.12, 95 CI:1.06, 1.18, p=<.0001; B symptoms: HR 16.48, 95 CI: 3.69, 73.60, p=.0002). However, the impact of B symptoms should be interpreted with caution as only 4% of pts presented with this at baseline. On UVA, each one-year increase in age was associated with an 8.5% rise in the risk of death. ECOG PS 1-2 was associated with worse OS on univariate analysis (HR 2.62, 95% CI 0.99, 6.93, p=.05), but was not significant on MVA (HR 1.05, 95% CI 0.368, 2.974, p=.93). Conclusions: In this large RWA of PCALCL, excellent long-term survival was observed with predominantly skin directed frontline therapies. The use of systemic treatments, including BV, was infrequent as first line therapy. Older age and poor PS were significant predictors for reduced survival.

A man in his 80s presented with 3 weeks of lower back pain, generalised weakness, poor appetite and intermittent melena, without genitourinary symptoms or recent trauma. CT showed an old L1 compression fracture and new sclerotic lesions in the L3 and L4 vertebrae, as well as mildly enlarged abdominal lymph nodes. 3 days later, he returned to the emergency department with worsening symptoms, including new left hemiparesis. A head CT revealed a right subdural haematoma (SDH) with a midline shift. Despite treatment for disseminated intravascular coagulation, the patient’s condition deteriorated, leading to a suspicion of spontaneous intracranial hypotension. An autopsy revealed disseminated metastatic adenocarcinoma with dura and leptomeningeal metastases, ultimately causing spontaneous SDH and subsequent transtentorial herniation. This case highlights the impact of anchoring bias in clinical decision-making and the importance of early recognition of underlying malignancy as the aetiology of spontaneous SDH in patients presenting with signs and symptoms of metastatic cancer.

An 18-year-old previously healthy Filipino male presented with abdominal pain, vomiting, dyspnoea and fever. Initial investigations revealed severe hepatosplenomegaly, pancytopaenia, elevated liver enzymes, coagulopathy and extremely high ferritin levels. Bone marrow biopsy confirmed an abnormal CD8+ T-cell population with haemophagocytosis. Extensive workup was performed, and he was ultimately diagnosed with haemophagocytic lymphohistiocytosis (HLH) secondary to Epstein-Barr virus-positive T-cell lymphoma of childhood (EBV-TCL), a rare and aggressive malignancy. Despite the initiation of modified dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide (SMILE) chemotherapy along with high-dose glucocorticoids, the patient did not respond to the treatment and expired. This case underscores the critical importance of early recognition and prompt intervention in EBV-TCL-associated HLH which is a unique condition and a rare entity. The diagnosis of this entity can be particularly challenging, given its rapid progression and high mortality rate. Therefore, timely diagnosis and the initiation of appropriate therapy are essential for improving patient outcomes. General medicine providers play a key role in identifying warning signs to avoid delays in treatment initiation.

Abstract Background Artificial intelligence (AI) has emerged as a tool to potentially increase the efficiency and efficacy of cardiovascular care and improve clinical outcomes. This study aims to provide an overview of applications of AI in cardiac surgery. Methods A systematic literature search on AI applications in cardiac surgery from inception to February 2024 was conducted. Articles were then filtered based on the inclusion and exclusion criteria and the risk of bias was assessed. Key findings were then summarized. Results A total of 81 studies were found that reported on AI applications in cardiac surgery. There is a rapid rise in studies since 2020. The most popular machine learning technique was random forest ( n = 48), followed by support vector machine ( n = 33), logistic regression ( n = 32), and eXtreme Gradient Boosting ( n = 31). Most of the studies were on adult patients, conducted in China, and involved procedures such as valvular surgery (24.7%), heart transplant (9.4%), coronary revascularization (11.8%), congenital heart disease surgery (3.5%), and aortic dissection repair (2.4%). Regarding evaluation outcomes, 35 studies examined the performance, 26 studies examined clinician outcomes, and 20 studies examined patient outcomes. Conclusion AI was mainly used to predict complications following cardiac surgeries and improve clinicians' decision‐making by providing better preoperative risk assessment, stratification, and prognostication. While the application of AI in cardiac surgery has greatly progressed in the last decade, further studies need to be conducted to verify accuracy and ensure safety before use in clinical practice.

Introduction: The real-world outcomes in patients (pts) with PCALCL in the era of targeted therapies like Brentuximab Vedotin (BV) is not well defined due to lack of large multicenter studies. We conducted a multicenter retrospective RWA to assess patient and disease characteristics, treatment patterns, survival outcomes and impact of novel therapies in this rare type of cutaneous T cell lymphoma (CTCL). Methods: A total of 95 adult (≥18 years) pts from 8 academic institutions in the United States diagnosed from 2010-2022 were included in the analysis. The study was approved by the Institutional Review Boards at the respective sites. Demographic and disease factors were summarized by descriptive statistics. Overall survival (OS) was estimated by Kaplan-Meier method and compared using log rank method. Results: In our cohort, the median age at diagnosis was 63 (range 18-93) years. The majority of pts were male 60%, white 79%, and had good performance status (PS) ECOG 0-1 (93%). Median time from initial presentation to diagnosis was 1.8 (range 0-211) months. Most common initial skin presentation was tumor 46% (44/95), followed by plaques 27% (26/95) and patches 15% (14/95). No pt presented with erythroderma. Median size of the largest lesion was 2 (range 0.5-20) cm. 63% had early stage (IA-IIA) disease and 86% had <5 skin lesions at the time of initial diagnosis. Furthermore, palpable lymph node (LN) (10%) and elevated LDH (18%) were uncommon at diagnosis. Initial treatments include localized radiation 60%, surgical excision 21% and topical steroids 11%. A small subset of pts received systemic treatments like CHOP 13% (12/95), BV 8% (8/95) and oral methotrexate 7% (7/95) as frontline therapy. A proportion of pts received XRT with CHOP (6/12) and BV (2/8). The overall response rate (ORR) to initial therapy was 68% (65/95) with 61% achieving a CR and 17% had primary refractory disease (stable and progressive disease). Relapse rate after 1st line therapy was 52% (49/95). In our cohort a total of 22 pts received BV after frontline therapy, of which 19 were BV naïve and 3 were re-treated. At the time of last follow up, 27% of our cohort were still on treatment, 78% were alive and 21% were dead; only 3% of deaths were attributed to the lymphoma. The median OS was 128 months (95% CI: 78.4-NA) (Figure 1) with a median follow up of 42 (range 0.5-123.5) months. The 5-year OS was 77%. On univariate analysis, older age (≥65 vs <65 years) (median OS 78 vs 128 months; p=0.004) and higher number of lesions (5-10 vs <5) (mOS 34 vs 128 months; p=<0.0001) were significant associated with OS (Table 1). Type and size of the skin lesions, presence of palpable LN, elevated LDH, stage, and treatment modalities had no impact on OS. Results of multivariate analysis will be presented at the conference. Conclusion: In this large multicenter RWA of PCALCL, excellent long-term survival was observed following frontline therapies that were mostly skin directed. The use of systemic therapies including BV were infrequent even in relapsed disease. Older age and increased number of skin lesions were associated with poor OS.

7530 Background: Oncolytic virotherapy is a novel immunomodulatory therapeutic approach currently under study for relapsed refractory (R/R) hematologic malignancies. The engineered Vesicular Stomatitis Virus VSV-IFNβ-NIS used in this study encodes interferon beta (IFNβ) and sodium iodine symporter (NIS). Virally-encoded IFNβ serves as an index of viral proliferation and enhances host anti-tumor immunity. Herein, we report the updated results of the phase 1 clinical trial NCT03017820 of a one-time administration of systemic VSV-IFNβ-NIS among patients (pts) with R/R multiple myeloma (MM), T cell Lymphoma (TCL) and Acute myeloid Leukemia (AML) with particular focus on the TCL cohort treated at the highest dose level (DL4) without Ruxolitinib. Methods: VSV-IFNβ-NIS was administered as a single IV dose following a classical 3+3 phase I trial, starting at 5e9 TCID50 DL1 through 1.7e11 TCID50 DL4. A dose expansion cohort of 8 additional R/R TCL pts was added at DL4 in view of an initial signal of activity. The primary objective was to determine the maximum tolerated dose of VSV-IFNβ-NIS as a single agent. Secondary objectives were determination of safety profile and preliminary efficacy of VSV-IFNβ-NIS. Adverse events (AEs) are reported based on CTCAE V4; cytokine release syndrome (CRS) grading was based on Lee (Blood 2014) criteria. Results: To date, a total of 43 pts received VSV-IFNβ-NIS: MM (N=21), TCL (N=21) and AML (N=1). In the TCL cohort: at DL4 Group A (no Ruxolitinib), 12 pts were registered, but only 11 pts were treated (mycosis fungoides (MF) N=3; ALK- ALCL N=1; PTCL-NOS N=2; AITL N=4; Nodal PTCL, TFH N=2; ages 33-79). These pts received a median of 3 lines of therapy (range: 1-5). No dose limiting toxicities were observed. Grades 3 and higher AEs were hematologic with transient lymphopenia (63.6%), neutropenia (36.4%) being the most common. The non-hematologic AEs observed included unique toxicities such as CRS grades 1-2 (81.8%); the transient transaminitis grade 1-2 (36.4%) and grade 3 (27.3%) along with thrombocytopenia grade 1-2 (63.6%) and grade 3 (18.2%) were a reflection IFNβ toxicity. All the AEs observed were short lived. Responses were seen in pts with PTCL. At DL4, in pts with systemic PTCL (N=9), there were 5 responses including 3 complete responses (CR) with two long-lasting at 24 months, an ongoing 15 month CR, and a 5 month CR, and 2 partial responses (PR) lasting 5 months in one pts and 6 months in the other. Conclusions: These updated results of single agent VSV-IFNβ-NIS which include pts with PTCL treated at the highest dose level and a dose expansion cohort demonstrates not only the safety of VSV-IFNβ-NIS but also a strong efficacy signal in pts with PTCL with impressive durable responses. Two expansion cohorts at DL4 have been added (20 additional PTCL, 10 B-cell lymphoma pts) to obtain additional data on tolerability and efficacy and biomarkers of response in these pts. Clinical trial information: NCT03017820 .

Objective: To investigate whether dexmedetomidine (DEX), as adjunctive therapy to benzodiazepine (BZD), is superior to BZD alone in critically ill patients with alcohol withdrawal syndrome (AWS). Data Sources: PubMed Central, Cochrane CENTRAL, ClinicalTrials.gov and Google Scholar were used as search databases. Specific keywords and MeSH terms were “dexmedetomidine,” “benzodiazepine,” and “alcohol withdrawal syndrome.” The last search was on September 16, 2022. Study Selection and Data Extraction: Randomized controlled trials (RCTs) and nonrandomized/cohort studies exploring the use of DEX in the management of AWS were included. A total of 12 studies were included in the systematic review and 7 in the meta-analysis. Data Synthesis: The intensive care unit length of stay (ICU LOS) was found to have a mean difference (MD) of 48.06 [37.48, 58.64], P = <0.001 for the cohort subgroup, significantly favoring the DEX arm, but, in contrast, pooled RCT data showed a result of –20.07 [–36.86, –3.28], P = 0.02, a shorter ICU LOS for the DEX arm. Bradycardia and hypotension incidence significantly favored the BZD arm in both subgroups. This study compares the effectiveness of adjunctive DEX in clinical practice and aims to help providers in critical decision-making by compiling and analyzing the best current available evidence of its use in AWS. Conclusions: Based on low to very low level of evidence, adjunctive DEX showed no significant difference for ICU LOS when compared with BZD alone. Pooled randomized trials potentially show a benefit but are similarly limited by their low quality of evidence.