Citations

INTRODUCTION: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE. METHODS: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1–6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year. RESULTS: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR. DISCUSSION: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).

AbstractInfection is a rare occurrence after revision anterior cruciate ligament reconstruction (rACLR). Because of the low rates of infection, it has been difficult to identify risk factors for infection in this patient population. The purpose of this study was to report the rate of infection following rACLR and assess whether infection is associated with patient‐ and surgeon‐dependent risk factors. We reviewed two large prospective cohorts to identify patients with postoperative infections following rACLR. Age, sex, body mass index (BMI), smoking status, history of diabetes, and graft choice were recorded for each patient. The association of these factors with postoperative infection following rACLR was assessed. There were 1423 rACLR cases in the combined cohort, with 9 (0.6%) reporting postoperative infections. Allografts had a higher risk of infection than autografts (odds ratio, 6.8; 95% CI, 0.9–54.5; p = .045). Diabetes (odds ratio, 28.6; 95% CI, 5.5–149.9; p = .004) was a risk factor for infection. Patient age, sex, BMI, and smoking status were not associated with risk of infection after rACLR.

The incidence, severity, and mortality of ongoing coronavirus infectious disease 19 (COVID-19) is greater in men compared with women, but the underlying factors contributing to this sex difference are still being explored. In the current study, using primary isolated human airway smooth muscle (ASM) cells from normal males versus females as a model, we explored the effect of estrogen versus testosterone in modulating the expression of angiotensin converting enzyme 2 (ACE2), a cell entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using confocal imaging, we found that ACE2 is expressed in human ASM. Furthermore, Western analysis of ASM cell lysates showed significantly lower ACE2 expression in females compared with males at baseline. In addition, ASM cells exposed to estrogen and testosterone for 24 h showed that testosterone significantly upregulates ACE2 expression in both males and females, whereas estrogen downregulates ACE2, albeit not significant compared with vehicle. These intrinsic and sex steroids induced differences may help explain sex differences in COVID-19.

Introduction: Nusinersen antisense oligonucleotide infusions have been shown to be effective in the treatment spinal muscular atrophy. The majority of the evidence has been collected in young type 1 and type 2 patients, and evidence of efficacy in adult patients is limited. Case Report: A 48-year-old woman with spinal muscular atrophy type 3 who has received the loading dose and 8 maintenance infusions over an 8-month period. Grip and pinch strength, measured by hand-held dynamometry measured at baseline and in 6 to 12 months interval improved over a 24-month period. She also reported multiple other subjective improvements in function. Conclusions: This is the first published case of nusinersen in a middle-aged adult with spinal muscular atrophy. Sustained clinically meaningful improvement may be possible with nusinersen initiation in mid adulthood.

Abstract Background: I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint risk to evaluate novel agents as neoadjuvant therapy for breast cancer. The primary endpoint is pathologic complete response (pCR, ypT0/is ypN0)). DNA repair deficiency in cancer cells can lead to immunogenic neoantigens, activation of the STING pathway, and PARP inhibition can also upregulate PD-L1 expression. Based on these rationales we tested the combination of durvalumab (anti-PDL1), olaparib (PARP inhibitor) and paclitaxel in I-SPY2. Methods: Women with tumors ≥ 2.5 cm were eligible for screening. Only HER2 negative (HER2-) patients were eligible for this treatment, hormone receptor positive (HR+) patients had to have MammaPrint high molecular profile. Treatment included durvalumab 1500 mg every 4 weeks x 3, olaparib 100 mg twice daily through weeks 1-11 concurrent with paclitaxel 80 mg/m2 weekly x 12 (DOP) followed by doxorubicin/cyclophosphamide (AC) x 4. The control arm was weekly paclitaxel x 12 followed by AC x 4. All patients undergo serial MRI imaging and imaging response at 3 & 12 weeks combined with accumulating pCR data are used to estimate, and continuously update, predicted pCR rate for the trial arm. Regimens “graduation with success” when the Bayesian predictive probability of success in a 300-patient phase 3 neoadjuvant trial in the appropriate biomarker groups reaches > 85%. Results: A total of 73 patients received DOP treatment including 21 HR- tumors (i.e. triple-negative breast cancer, TNBC) and 52 HR+ tumors between May 2018 - June 2019. The control group included 299 patients with HER2- tumors. The DOP arm graduated in June 2019, 13 months after enrollment had started, for all HER2- negative and the HR+/HER2- cohorts with > 0.85% predictive probabilities of success. 72 patient completed surgery and evaluable for pCR, the final predicted probabilities of success in a future phase III trial to demonstrate higher pCR rate with DOP compared to control are 81% for all HER2- cancers (estimated pCR rate 37%), 80% for TNBC (estimated pCR rate 47%) and 74.5% for HR+/HER2- patients (estimated pCR rate 28%). Association between pCR and germline BRCA status and immune gene expression including PDL1 will be presented at the meeting. No unexpected toxicities were seen, but 10 patients (14%) had possibly immune or olaparib related grade 2/3 AEs (3 pneumonitis, 2 adrenal insufficiency, 1 colitis, 1 pancreatitis, 2 elevated LFT, 1 skin toxicity, 2 hypothyroidism, 1 hyperthyroidism, 1 esophagitis). Conclusion: I-SPY2 demonstrated a significant improvement in pCR with durvalumab and olaparib included with paclitaxel compared to chemotherapy alone in women with stage II/III high-risk, HER2-negative breast cancer, improvement was seen in both the HR+ and TNBC subsets. Citation Format: Lajos Pusztai, Hyo S. Han, Christina Yau, Denise Wolf, Anne M. Wallace, Rebecca Shatsky, Teresa Helsten, Judy C. Boughey, Tufia Haddad, Erica Stringer-Reasor, Carla Falkson, A. Jo Chien, Rita Mukhtar, Anthony Elias, Borges Virginia, Rita Nanda, Douglas Yee, Kevin Kalinsky, Kathy S. Albain, Aixa Soyano Muller, Kathleen Kemmer, Amy S. Clark, Claudine Isaacs, Alexandra Thomas, Nola Hylton, W. Fraser Symmans, Jane Perlmutter, Michelle Melisko, Hope S. Rugo, Richard Schwab, Amy Wilson, Amy Wilson, Ruby Singhrao, Smita Asare, Laura J. van't Veer, Angela M. DeMichele, Ashish Sanil, Donald A. Berry, Laura J. Esserman, Trial Consortium I-SPY 2. Evaluation of durvalumab in combination with olaparib and paclitaxel in high-risk HER2 negative stage II/III breast cancer: Results from the I-SPY 2 TRIAL [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT011.