Citations

Abstract Introduction: Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed hematologic cancer, with many patients diagnosed at a later stage in life and typically with comorbidities that often complicate CLL management. Atrial fibrillation (AF) is the most common arrhythmia in the United States and is associated with high hospitalization and mortality rates. While the relationship between CLL and AF has been reported, there is limited real-world evidence on the clinical and economic impact of AF in CLL patients. The objectives of this study were to examine the impact of AF on cardiovascular (stroke, bleeding events, heart failure) and economic (costs and healthcare resource utilization [HRU]) outcomes among patients with CLL. Methods: This retrospective observational study used the IBM MarketScan Research Databases in Treatment Pathways that includes at least a 10-million sample of the commercial and Medicare supplemental claims database. Patients who were at least 18 years, diagnosed with CLL (identified by ICD-9/ICD-10) and continuously enrolled from January 2009 to July 2020 were included. CLL patients were followed up for one year after their first CLL diagnosis date to examine the incidence of AF. Cardiovascular outcomes were evaluated as the incidence of stroke, bleeding events, and heart failure among the CLL patients with and without AF. Costs and HRU were assessed following up until 1 year after the first date of AF, stroke, bleeding events, and heart failure. HRU was evaluated for outpatient, emergency room (ER), inpatient, and pharmacy visits, and by length of stay (LOS) for hospitalizations. Costs were evaluated in overall population and by HRU type. Statistical differences in clinical outcomes between patients with and without AF were compared using chi-square tests. The Mann Whitney Wilcoxon test was used to compare the medians for the HRU and cost outcomes. The associations between AF and hospitalizations as well as costs were evaluated by multivariable logistic regression and generalized linear model, respectively. Statistical significance was determined at a P-value of less than 0.05. Results: Among the total of 23,756 newly diagnosed CLL patients (median age 68 years, 57.83% male) included in the study, 11% had AF within 1 year of the CLL diagnosis. CLL patients who had AF were significantly older (median age: 67 vs 82 years) and had more male patients (56.9% vs 65.1%) compared to CLL patients without AF. Significantly higher rates of stroke (12.67% vs. 4.97%), bleeding events (17.45% vs. 8.53%), and heart failure (31.14% vs. 4.70%) were observed in CLL patients with AF than those without (Figure 1). Compared to the CLL cohort without AF, adjusted regression analysis indicated that overall, CLL cohort with AF was twice as likely to be hospitalized (odds ratio [OR]=2.03) and incurred 44% higher total costs (cost ratio [CR]=1.44). Further examining the impact of AF-related cardiovascular outcomes, we observed that CLL patients with AF who developed stroke, bleeding events, and heart failure had statistically significant higher HRU (outpatient, ER, inpatient, and pharmacy visits), longer LOS, and costs (total, outpatient, pharmacy) than CLL patients without AF. After adjusting for demographic and clinical confounders, significantly higher hospitalization rates and costs were also reported in the CLL cohort who had AF with further stroke (OR=2.59; CR=1.36), bleeding events (OR=3.27; CR=2.03), and heart failure (OR=5.47; CR=2.07) compared to the CLL cohort without AF. Conclusions: The findings of this real-world study demonstrated significantly higher hospitalizations, cardiovascular events, and economic burden incurred by CLL patients who had AF than those without. The presence of stroke, bleeding events, heart failure among CLL patients with AF further increased the HRU and costs. This study highlighted the importance of better disease management, more intentional monitoring for AF and improved CLL therapeutics with a lower risk of AF or cardiovascular toxicity to prevent or minimize the incidence of AF in CLL patients. Figure 1 Figure 1. Disclosures Mohan: BeiGene, Ltd.: Current Employment. Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Dick: IBM Watson Health: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Chanan-Khan: Ascentage: Research Funding; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; Cellectar: Current equity holder in publicly-traded company; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; BeiGene, Jansen, Ascentage: Honoraria; BieGene, Jansen, Ascentage: Consultancy.

Abstract Background: Treatment of multiple myeloma (MM) commonly encompasses combination of drugs within the three drug classes including proteasome inhibitors (PIs), immunomodulators and (IMiDs), and monoclonal antibodies, both for newly diagnosed and relapsed disease. With increasing appreciation of disease heterogeneity based on underlying genetic abnormality, and demonstration of efficacy of venetoclax in patients with t(11;14) MM, the outcomes with commonly used MM regimens among the different cytogenetic subgroups are of great interest. Venetoclax, a BCL-2 inhibitor, is being studied in t(11;14) positive MM patients who have received at least two prior lines of treatment (NCT03539744; CANOVA). However, outcomes in previously treated t(11;14) MM patients using standard of care approaches in the real-world setting is limited. Patients and methods: This non-interventional, retrospective observational cohort study included patients with t(11;14) MM from the International Myeloma Working Group (IMWG) retrospective study of t(11;14) MM. From the overall cohort, patients with t(11;14) MM receiving pomalidomide + dexamethasone (PomDex) in ≥3 rd line were selected, similar to those being enrolled in the ongoing CANOVA trial. Patients were also required to have prior exposure to lenalidomide and a PI without a history of transplant within 16 weeks prior to PomDex initiation. Patients enrolled in a clinical trial were excluded. Overall best response, time to next therapy (TTNT) as a surrogate measure for progression-free survival (PFS) and overall survival (OS) were assessed after initiation of PomDex. All analyses were descriptive in nature and were conducted using SAS 9.4 (SAS Institute Inc., Cary, NC, USA). Results: Fifty-two patients who met the inclusion criteria were analyzed. Median age was 63 years, 60% were male. Patients had a median of 3 prior lines at start of PomDex, at a median of 4.3 years from diagnosis; 52% had a prior transplant. A PR or better was observed in 34% of patients with PomDex. The median TTNT for this cohort was 6.1 months and median OS was 19.2 months. Conclusion: This retrospective study of non-trial patients with t(11;14) MM provides a benchmark for newer therapies in this patient population for comparison with both venetoclax dexamethasone in the ongoing CANOVA study as well as combinations using the pomalidomide backbone. Disclosures Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company. Kumar: Roche-Genentech: Consultancy, Research Funding; Bluebird Bio: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Novartis: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Antengene: Consultancy, Honoraria; Oncopeptides: Consultancy; Beigene: Consultancy; Tenebio: Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Gonzalez De La Calle: Celgene-BMS, Janssen, Amgen: Honoraria. Mangiacavalli: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria; BMS: Honoraria. Kastritis: Janssen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Genesis Pharma: Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Esteves: AbbVie: Consultancy; BMS: Consultancy; Amgen: Consultancy; Janssen: Consultancy. Delforge: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yee: Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy; Oncopeptides: Consultancy; Adaptive: Consultancy; GSK: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Sanofi: Consultancy. Arriola: AbbVie: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Ross: AbbVie: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Manthena: AbbVie: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Durie: Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda: Consultancy; Amgen: Other: fees from non-CME/CE services .

ObjectiveThe relative risk of SARS–CoV‐2 infection and COVID‐19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS–CoV‐2 infection in those with RMDs and describe clinical outcomes of COVID‐19 in these patients.MethodsWe conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS–CoV‐2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID‐19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle‐Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel‐Haenszel formula with random effects models.ResultsOf the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta‐analyses, we identified an increased prevalence of SARS–CoV‐2 infection in patients with an RMD (RR 1.53 [95% CI 1.16–2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08–2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID‐19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD.ConclusionPatients with RMDs have higher rates of SARS–CoV‐2 infection and an increased mortality rate.

Abstract BACKGROUND Total en bloc sacrectomy provides the best long-term local control for large primary bony sacral tumors, but often requires lumbosacral nerve root sacrifice leading to loss of ambulation and/or bowel, bladder, and/or sexual dysfunction. Nerve-sparing techniques may be an option for some patients that avoid these outcomes and accordingly improve postoperative quality of life. OBJECTIVE To describe the technique for a posterior-only en bloc hemisacrectomy with maximal nerve root preservation and to summarize the available literature. METHODS A 38-yr-old woman with a 7.7 × 5.4 × 4.5 cm biopsy-proven grade 2 chondrosarcoma involving the left L5-S2 posterior elements underwent a posterior-only left hemisacrectomy tri-rod L3-pelvis fusion. A systematic review of the English literature was also conducted to identify other descriptions of high sacrectomy with distal sacral nerve root preservation. RESULTS Computer-aided navigation facilitated an extracapsular resection that allowed preservation of the left-sided L5 and S3-Co roots. Negative margins were achieved and postoperatively the patient retained ambulation and good bowel/bladder function. Imaging at 9-mo follow-up showed no evidence of recurrence. The systematic review identified 4 prior publications describing 6 total patients who underwent nerve-sparing sacral resection. Enneking-appropriate resection was only obtained in 1 case though. CONCLUSION Here we describe a technique for distal sacral nerve root preservation during en bloc hemisacrectomy for a primary sacral tumor. Few prior descriptions exist, and the present technique may help to reduce the neurological morbidity of sacral tumor surgery.

AbstractBackgroundThe anatomical structure around the pancreatic head is very complex and it is important to understand its precise anatomy and corresponding anatomical approach to safely perform minimally invasive pancreatoduodenectomy (MIPD). This consensus statement aimed to develop recommendations for elucidating the anatomy and surgical approaches to MIPD.MethodsStudies identified via a comprehensive literature search were classified using the Scottish Intercollegiate Guidelines Network method. Delphi voting was conducted after experts had drafted recommendations, with a goal of obtaining >75% consensus. Experts discussed the revised recommendations with the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting.ResultsThree clinical questions were addressed, providing six recommendations. All recommendations reached at least a consensus of 75%. Preoperatively evaluating the presence of anatomical variations and superior mesenteric artery (SMA) and superior mesenteric vein (SMV) branching patterns was recommended. Moreover, it was recommended to fully understand the anatomical approach to SMA and intraoperatively confirm the SMA course based on each anatomical landmark before initiating dissection.ConclusionsMIPD experts suggest that surgical trainees perform resection based on precise anatomical landmarks for safe and reliable MIPD.

Abstract Background and study aims En bloc endoscopic mucosal resection (EMR) is preferred over piecemeal resection for polyps ≤ 20 mm. Data on colorectal EMR training are limited. We aimed to evaluate the en bloc EMR rate of polyps ≤ 20 mm among advanced endoscopy trainees and to identify predictors of failed en bloc EMR. Methods This was a multicenter prospective study evaluating trainee performance in EMR during advanced endoscopy fellowship. A logistic regression model was used to identify the number of procedures and lesion cut-off size associated with an en bloc EMR rate of ≥ 80 %. Multivariate analysis was performed to identify predictors of failed en bloc EMR. Results Six trainees from six centers performed 189 colorectal EMRs, of which 104 (55 %) were for polyps ≤ 20 mm. Of these, 57.7 % (60/104) were resected en bloc. Trainees with ≥ 30 EMRs (OR 6.80; 95 % CI: 2.80–16.50; P = 0.00001) and lesions ≤ 17 mm (OR 4.56;95 CI:1.23–16.88; P = 0.02) were more likely to be associated with an en bloc EMR rate of ≥ 80 %. Independent predictors of failed en bloc EMR on multivariate analysis included: larger polyp size (OR:6.83;95 % CI:2.55–18.4; P = 0.0001), right colon location (OR:7.15; 95 % CI:1.31–38.9; P = 0.02), increased procedural difficulty (OR 2.99; 95 % CI:1.13–7.91; P = 0.03), and having performed < 30 EMRs (OR: 4.87; 95 %CI: 1.05–22.61; P = 0.04). Conclusions In this pilot study, we demonstrated that a relatively low proportion of trainees achieved en bloc EMR for polyps ≤ 20 mm and identified procedure volume and lesion size thresholds for successful en bloc EMR and independent predictors for failed en bloc resection. These preliminary results support the need for future efforts to define EMR procedure competence thresholds during training.

Assessment of lung biopsies for the diagnosis of hypersensitivity pneumonitis (HP) is one of the most difficult diagnostic problems for surgical pathologists. It is a form of interstitial lung disease resulting from an immune reaction provoked by an inhaled antigen in susceptible individuals. Although this definition sounds simple, in practice, the diagnosis of HP can be challenging. To address these issues, the American College of Chest Physicians (CHEST) has recently published a guideline for the diagnosis of HP. In this review, we will explore the multidisciplinary diagnostic evaluation of HP with a focus on the pathologic features as outlined in the CHEST guidelines. The histologic criteria are divided into 4 diagnostic categories: (1) Typical nonfibrotic HP or fibrotic HP; (2) Compatible with nonfibrotic HP or fibrotic HP; (3) Indeterminate for nonfibrotic or fibrotic HP; and (4) Alternative Diagnosis. It is important to emphasize that patterns 1 to 3 do not represent discrete histologic entities or pathologic diagnoses. Rather, these categories are meant to serve as a practical guide for organizing a complex set of overlapping histologic patterns into an integrated diagnostic framework for facilitating multidisciplinary discussion. High-resolution computed tomography features are also summarized, emphasizing how the correlation of lung biopsies with computed tomography findings can help to favor the diagnosis, particularly in cases where biopsies are not typical for HP. This review highlights details of the histologic spectrum of HP as well as the utility of different types of biopsies and bronchoalveolar lavage. We also emphasize the importance of multidisciplinary discussion and the complex differential diagnosis.

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.