Citations

AbstractClinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant‐eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)‐based regimens before ASCT. Study endpoints included event‐free survival (EFS), progression‐free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI‐based regimens prior to ASCT. When adjusted for time to relapse, pre‐ASCT response and use of BV maintenance, patients receiving CPI‐based regimens had superior 2‐year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI‐based regimens were associated with superior 2‐year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03–0.5, p < .0001). OS did not differ by pre‐ASCT salvage regimen. In this large multicenter retrospective study, CPI‐based regimens improved EFS and PFS compared to other salvage regimens independent of pre‐ASCT response. These data support earlier sequencing of CPI‐based regimens in R/R cHL in the pre‐ASCT setting.

Abstract The chain specificities of 18 Ak and 26 Ab-reactive anti-Ia monoclonal antibodies have been determined. L cells were transfected with haplotype-matched (A alpha k:A beta k, A alpha b:A beta b) or haplotype-mismatched (A alpha k:A beta b, A alpha b:A beta k) cDNA pairs, lines expressing high levels of surface A complex were selected, and antibody reactivity with a panel of reagents was assessed by cytofluorimetric analysis. Most of the antibodies recognized a determinant specified by one chain, either alpha or (more commonly) beta. A few examples of more complex determinants were also observed. A knowledge of the chain specificities of anti-Ia monoclonal antibodies should prove useful for a variety of studies aimed at dissecting Ia structure-function relationships.

Abstract A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits. Secondary analyses using alternative instruments and sensitivity analyses assessing potential violations of MR assumptions were conducted. Genetically predicted morning preference was associated with 13% lower risk of CRC in men (ORIVW = 0.87, 95% CI = 0.78, 0.97, P = 0.01), but not in women or in both sexes combined. Τhis association remained consistent in some, but not all, sensitivity analyses and was very similar for colon and rectal cancer. There was no evidence of an association for any other sleep trait. Overall, this study provides little to no evidence of an association between genetically predicted sleep traits and CRC risk.

AbstractIntroductionA current limitation of single chamber implantable cardioverter defibrillators (ICDs) is the lack of an atrial lead to reliably detect atrial fibrillation (AF) episodes. A novel ventricular based atrial fibrillation (VBAF) detection algorithm was created for single chamber ICDs to assess R‐R variability for detection of AF.MethodsPatients implanted with Visia AF™ ICDs were prospectively enrolled in the Medtronic Product Surveillance Registry from December 15, 2015 to January 23, 2019 and followed with at least 30 days of monitoring with the algorithm. Time to device‐detected daily burden of AF ≥ 6 min, ≥6 h, and ≥23 h were reported. Clinical actions after device‐detected AF were recorded.ResultsA total of 291 patients were enrolled with a mean follow‐up of 22.5 ± 7.9 months. Of these, 212 (73%) had no prior history of AF at device implant. However, 38% of these individuals had AF detected with the VBAF algorithm with daily burden of ≥6 min within two years of implant. In these 80 patients with newly detected AF by their ICD, 23 (29%) had a confirmed clinical diagnosis of AF by their provider. Of patients with a clinical diagnosis of AF, nine (39%) were newly placed on anticoagulation, including five of five (100%) patients having a burden >23 h.ConclusionsContinuous AF monitoring with the new VBAF algorithm permits early identification and actionable treatment for patients with undiagnosed AF that may improve patient outcomes.

Abstract Background: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. Methods: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. Results: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10−8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20–1.30] compared with the other genotypes (OR &lt;1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10−8) and 8q24.23 (rs7005722, P = 2.88 × 10−8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09–1.16) compared with the other genotypes (OR &lt;1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07–1.28) compared with the other genotypes (OR &lt;1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Conclusions: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. Impact: These findings can guide potential prevention treatments.

Background: Regional anesthesia (“block”) is an important component of upper extremity (UE) surgery pain control. However, little is known about patient experience related to perioperative opioid use. This study assessed patient-reported pain control and satisfaction with UE blocks and evaluated how opioid consumption impacted these outcomes before the block “wore off.” Methods: A postoperative phone survey was administered to patients who underwent outpatient UE surgery at a surgery center for more than 16 months. It assessed pain scores (scale 1-10), satisfaction with block duration (scale 1-5), duration until return of UE function, and opioid consumption. Analyses used Mann-Whitney U tests, Fisher exact tests, and bivariate and multivariable linear and ordered logistic regressions to understand relationships between opioid use and outcomes. Results: A total of 509 patients (61%) completed the survey, and 441 (88%) were satisfied with block duration. Initial and final pain scores were significantly higher in patients who took opioids prior to the block wearing off (6 and 4.5, P = .04 and 3.5 and 2, P = .002, respectively). Although satisfaction with block duration was not different in group comparisons (ie, patients who premedicated vs those who did not), in a multivariable analysis, patients who premedicated with opioids had 78% increased odds of reporting the highest level of satisfaction compared with the lower 4 levels ( P = .03). Conclusions: Upper extremity blocks are associated with high overall patient satisfaction and postsurgical pain control. Premedicating before the block wears off may increase patient satisfaction with block duration even if pain is not notably impacted.

Abstract Background While numerous, most described cases of myocarditis and pericarditis following COVID-19 vaccination are mild and self-limited. We present two cases of life-threatening cardiac tamponade following COVID-19 vaccination. Methods Two cases of cardiac tamponade in temporal association with COVID-19 vaccination were reviewed Results Case 1 : 75-year-old male with rheumatoid arthritis admitted with chest pressure and hypotension 2 days after his 1st dose of Pfizer-BioNTech COVID-19 vaccine. Pericardiocentesis removed 275 ml of exudative effusion with 14,140 nucleated cells/ml. Fluid bacterial and fungal cultures were negative; cytology was inconsistent with malignancy. He had no Epstein-Barr virus (EBV) or cytomegalovirus (CMV) viremia. Symptoms resolved on prednisone and colchicine. A week later, he had an uneventful second COVID-19 vaccine. He went on to have 3 recurrences of pericarditis starting two months after his first. One was within 48 hours of his COVID-19 booster. He is on long term prednisone. Case 2: 66-year-old male with non-Hodgkin’s lymphoma in remission. He developed chest pain a day after his 2nd dose of Pfizer-BioNTech COVID-19 vaccine. Admitted 4 days later with pericardial effusion and managed medically. Readmitted a week later with fever and chest pain. Echocardiogram now showed cardiac tamponade. Pericardiocentesis removed 400 ml of exudative fluid with 1,191 nucleated cells/mL. Cultures for bacteria, fungi, and mycobacteria were negative. Cytology didn't show malignancy. Serologies for CMV, EBV and parvovirus represented past infection. He was discharged with a pericardial drain, colchicine, and NSAIDs. He was later readmitted with fevers. Echocardiogram only showed small pericardial effusion, which did not require drainage. Figure 1Circumferential pericardial effusion seen on trans-thoracic echocardiography from patient in case 1. Conclusion Given the proximity to COVID-19 vaccination and lack of alternative explanations, we believe that tamponade was a direct result of post-vaccine inflammatory pericarditis. Neither patient had a prior history of pericardial effusion. Both tested negative for SARS-CoV-2 by nasopharyngeal swab excluding active infection. Healthcare providers should consider the possibility of pericardial effusion and tamponade in patients with chest pain, shortness of breath, or hypotension following COVID-19 vaccination. Disclosures All Authors: No reported disclosures.

Adolescents and young women (AYA) with breast cancer represent a unique patient population, compared to the general population with breast cancer. We performed a literature review to evaluate the factors that influenced the surgical outcomes in this patient population. Fifty-two studies were identified, which evaluated breast surgery type, axillary surgery, contralateral prophylactic mastectomy (CPM), surgical timing, psychological factors, disparities, and imaging use. AYA patients had equivalent oncologic outcomes with breast conserving surgery (BCS) or mastectomy. CPM did not improve survival. There are limited data on axillary management in the AYA population, and while more data would be beneficial, this is currently extrapolated from the general breast cancer population. A shorter time to initiate treatment correlated to better outcomes, and disparities need to be overcome for optimal outcomes. AYA patients appreciated involvement in clinical decisions, and shared decision making should be considered whenever possible. Providers must keep these factors in mind when counseling AYA patients, regarding the surgical management of breast cancer.