Kristen Marie Sanfilippo

Patients with myeloproliferative neoplasms (MPN) are at risk of splanchnic vein thrombosis (SVT). Previous studies have failed to demonstrate a benefit of hydroxyurea therapy in preventing recurrent thrombosis after SVT, but they are limited by small sample sizes and inability to account for starting, stopping, or switching of cytoreductive therapies. To better assess the impact of cytoreductive therapy on thrombosis recurrence, we performed a retrospective cohort study of patients with MPN-SVT from the international GASTRO-MPN consortium, treating cytoreductive therapy as a time-dependent covariate. We identified 757 patients, of whom 43% were treated with cytoreductive therapy. During a median follow-up of 7.4 years, 256 patients (34%) had thrombosis recurrence; 145 (19%) had SVT extension/recurrence/transjugular intrahepatic portosystemic shunt thrombosis, and 138 (18%) had a thrombosis recurrence outside the splanchnic bed (74% were venous). In addition, 262 patients (35%) experienced clinically relevant bleeding and 170 (22%) died. After adjusting for age, sex, previous thrombosis, timing of MPN diagnosis relative to SVT, anticoagulation initiation within 30 days of SVT diagnosis, MPN type, JAK2 status, other cancers and cirrhosis, cytoreductive therapy was associated with a decreased risk of recurrent thrombosis (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.50-0.89; P = .01). This was driven by a lower risk of SVT extension/recurrence (HR, 0.62; 95% CI, 0.42-0.90; P = .01) but not by extra-splanchnic thrombosis recurrence (HR, 0.97; 95% CI, 0.72-1.30; P = .82). In a subgroup of patients without erythrocytosis/thrombocytosis at initial SVT (n = 275), cytoreductive therapy was associated with an HR of 0.65 (95% CI, 0.40-1.07; P = .09) for recurrent thrombosis. These data support the use of cytoreductive therapy for patients with MPN-SVT to prevent recurrent thrombosis, particularly SVT extension/recurrence.

Introduction: Differentiating tumor thrombus from bland thrombus can be challenging. This study assessed the diagnostic performance of positron emission tomography–computed tomography (PET/CT) scans in differentiating bland versus tumor thrombi in patients with cancer. Methods: We systematically searched for observational studies evaluating the diagnostic accuracy of PET/CT scans in differentiating tumor from bland thrombi in adult cancer patients. We included patients with suspected tumor or bland thrombus on PET/CT who underwent histopathological evaluation and/or confirmatory imaging or clinical follow‐up. Sensitivity and specificity were estimated using a random‐effects model. Positive and negative likelihood ratios (LR+ and LR−) and diagnostic odds ratio (DOR) were derived from the pooled estimates. Results: Five studies were included (217 patients; mean age 55.9 years). Hepatobiliary malignancies (49%) and renal tumors (24%) were the most frequent, with the renal vein, portal vein, and inferior vena cava most frequently involved. Maximum standardized uptake value (SUVmax) was significantly higher in malignant compared to bland thrombi, with reported diagnostic cutoffs ranging from 2.25 to 3.63. PET/CT scan showed diagnostic accuracy with pooled sensitivity 92.2%, specificity 94.2%, LR− 0.121, LR+ 10.919, and DOR of 91.770. Conclusion: PET/CT scan may be beneficial in distinguishing tumor from bland thrombus in cancer patients.

Objectives: Evidence guiding the optimal timing of mechanical thrombectomy for patients presenting with intermediate-risk pulmonary embolism (PE) is limited. We aimed to evaluate whether the timing of mechanical thrombectomy is associated with improved clinical outcomes in this patient population. Design, Setting, and Patients: This multicenter, retrospective cohort study was conducted at five large academic hospitals. In total, 290 patients presenting with intermediate-risk PE who were treated with mechanical thrombectomy were included for analysis. The primary outcome was in-hospital mortality. Using generalized estimated equation, we compared the odds of in-hospital mortality for patients undergoing early intervention (EI; mechanical thrombectomy < 12 hr after PE diagnosis) vs. those undergoing delayed intervention (DI; mechanical thrombectomy ≥ 12 hr after diagnosis) while comparing for PE severity and other confounders. Interventions: None. Measurements and Main Results: EI was performed in 179 patients (61.7%), while 111 patients (38.3%) received DI. Unadjusted mortality did not differ significantly between groups (7.3% [13/179] vs. 10.8% [12/111]; p = 0.39). After adjusting for the Pulmonary Embolism Severity Index and Composite Pulmonary Embolism Shock scores, timing of intervention did not influence mortality (odds ratio, 1.80; 95% CI, 0.82–3.95; p = 0.14). However, patients in the EI group had greater reductions in in pulmonary artery systolic pressure (–25.8% [17.0] vs. –18.9% [17.1]; p = 0.020 and mean pulmonary artery pressure, –26.8% [17.7] vs. –20.2% [19.7]; p = 0.016) and lower rates of intubation (8.9% [16/179] vs. 18% [20/111]; p = 0.028). Conclusions: In patients presenting with intermediate-risk PE, timing of mechanical thrombectomy did not influence in-hospital mortality. EI may result in greater reductions in pulmonary artery pressures and decreased incidence of intubation compared with DI.

Multiple myeloma (MM) is the most common plasma cell dyscrasia in the United States with tremendously high burden. MM is preceded by a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS). Although several risk factors for progression have been identified (e.g., older age, male sex, black race, obesity, chemical exposure), their relative contributions remain unclear. Unlike other malignancies, such evidence is lacking for MM despite its high burden. To identify potential intervention strategies that can effectively prevent progression in patients with MGUS, we quantified contributions of the identified modifiable risk factors in the United States Veteran population with MGUS. Compared to the general population, this population is particularly vulnerable to MM as its higher proportions of male and older age as well as the potential prior Agent Orange exposure. We conducted a retrospective cohort study in the Veterans Health Administration and calculated multivariable‐adjusted population attributable fractions (aPAFs) of progression accounting for competing risk of death. The aPAF estimates the proportion of progression burden in the population with MGUS that is statistically attributable to a specific risk factor, independent of other factors. In the cohort of 35,073 Veterans with MGUS, among all evaluated risk factors (both modifiable and non‐modifiable), excess body mass index (BMI ≥25 kg/m ² ) was the leading factor (Black: aPAF = 27.1%, 95% CI 19.5%–34.0%; White: 27.2%, 95% CI 20.3%–33.4%; All: aPAF = 27.1%, 95% CI 22.1%–31.9%). Our study highlights the potential of weight management and lifestyle modification for informing the design of targeted MM prevention strategies for Veterans diagnosed with MGUS.

The incidence of venous thromboembolism (VTE) in patients with acute lymphoblastic leukemia (ALL) receiving asparaginase-based induction is high despite primary thromboprophylaxis. Our aim was to derive and externally validate a VTE risk prediction model in patients with ALL receiving asparaginase-based induction. We conducted a multicenter retrospective cohort study of patients (aged ≥18 years) with newly diagnosed ALL receiving asparaginase-based induction. The derivation and external validation cohorts included 306 and 94 patients, respectively. Primary outcome was VTE at any site. A cause-specific Cox proportional hazards model stratified by thromboprophylaxis and center was performed to identify VTE risk factors in the derivation cohort. A risk prediction model for VTE at 30 days was derived using variables with P value < .05 in the multivariable model and was tested in the validation cohort. VTE risk factors on multivariable analysis in the derivation cohort included D-dimer ≥1 μg fibrinogen equivalent unit per mL (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.07-6.5) and hemoglobin (HR for each 1 g/dL increment, 1.19; 95% CI, 1.06-1.34) at ALL diagnosis. A VTE risk score based on these variables distinguished between a 4% (95% CI, 0.72-12) and 20% (95% CI, 14-27) 30-day cumulative incidence of VTE in the derivation cohort, with similar findings in the validation cohort (area under the curve, 0.56). The negative predictive value for VTE at 30 days was 96% and 93% in the derivation and validation cohorts, respectively, and the positive predictive value was 20% in both. We derived and validated a model using D-dimer and hemoglobin, which stratifies VTE risk in patients with ALL receiving asparaginase-based induction.

Background: Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased risk of cardiovascular disease (CVD). However, its potential to provide additional prognostic information beyond traditional CVD risk assessments remains unknown. This study aimed to examine the association between MGUS and incident CVD and to determine whether MGUS status offers additional prognostic value beyond the established atherosclerotic cardiovascular disease risk calculation. Methods: We conducted a retrospective, matched observational study using 2010 to 2021 Veterans Health Administration data. MGUS status, confirmed through a validated natural language processing algorithm, were 1:5 matched to individuals without MGUS. The outcome of interest was an incident CVD event. Cumulative incidence functions were compared using Gray’s test. Multivariable Fine and Gray’s subdistribution models were performed to estimate the adjusted hazard ratios (aHRs) for incident CVD. Analyses were also stratified by atherosclerotic CVD risk category (low/borderline, intermediate, high). Results: The analytic cohort included 70 320 individuals (11 720/58 600 with/without MGUS); MGUS was associated with a higher 10‐year CVD incidence (29.5% versus 9.7%; P P P <0.001). Conclusions: MGUS is an independent risk factor of incident CVD across all atherosclerotic CVD risk categories in a heterogeneous cohort of US veterans. These findings underscore the connection between the immune system and CVD and suggest that determination of MGUS status is of clinical utility in adults at risk for CVD.