Citations

Abstract Background: In contrast to the rapid increase in thyroid cancer (TC) incidence, thyroid cancer mortality has remained low and stable over the last decades. In Ecuador, however, TC mortality has increased. The objective of this study is to determine possible drivers of high rates of thyroid cancer mortality, through a cross-sectional analysis of all patients attending a thyroid cancer referral center in Ecuador.Methods: From June 2014 to December 2017, a cross-sectional study was conducted at the Hospital de Especialidades Eugenio Espejo (HEEE), a regional reference public hospital for endocrine neoplasia in adults in Quito, Ecuador. We identified the mechanism of detection, histopathology and treatment modalities from a patient interview and review of clinical records. Results: Among 452 patients, 74.8% were young adults and 94.2% (426) were female. 13.7% had a family history of thyroid cancer, and patients’ median tumor size was 2 cm. The incidental finding was 54.2% whereas 45.8% was non-incidental. Thyroid cancer histology reported that 93.3% had papillary thyroid cancer (PTC), 2.7% follicular, 1.5% Hurtle cells, 1.6% medullary, 0.7% poor differentiated, and 0.2% anaplastic carcinoma. The mean MACIS (metastasis, age, completeness, invasion, and size) score was 4.95 (CI 4.15-5.95) with 76.2% of the thyroid cancer patients having MACIS score less than or equal to 6. The very low and low risk of recurrence was 18.1% (79) and 62% (271) respectively. An analysis of 319 patients with non-metastatic thyroid cancer showed that 10.7% (34) of patients had surgical complications. Moreover, around 62.5% (80 from 128 patients with thyroglobulin laboratory results) of TC patients had a stimulated-thyroglobulin (sTg) value equal or higher than 2 ng/ml. Overall, a poor surgical outcome was present in 35.1% (112) patients. Out of 436 patients with differentiated thyroid carcinoma (DTC), 86% (375) received radioactive iodine (RAI). Conclusion: Thyroid cancer histological characteristics and method of diagnosis are like those described in other reports without any evidence of the high frequency of aggressive thyroid cancer histology. However, we observed evidence of overtreatment and poor surgical outcomes that demand additional studies to understand their association with thyroid cancer mortality in Ecuador.

SummaryIbrutinib is associated with durable responses in patients with Waldenström macroglobulinaemia (WM). We hypothesized that response depth is predictive of progression‐free survival (PFS) in WM patients treated with ibrutinib. Using landmark analyses, we evaluated response depth in two cohorts of WM patients treated with ibrutinib monotherapy. The learning cohort was composed of 93 participants from two clinical trials, and the validation cohort of 190 consecutive patients treated off clinical trial. Rates of partial response (PR) or better at six months in learning and validation cohorts were 64% and 71% respectively (P = 0·29). In the learning cohort, three‐year PFS rates for patients who attained PR or better at six monthsversusnot were 81% and 57% respectively (P = 0·009). In the validation cohort, three‐year PFS rates for patients who attained PR or better at six monthsversusnot were 83% and 54% respectively (P = 0·008). In multivariate analyses, attaining PR or better at six months was associated with superior PFS in the learning [hazard ratio (HR) 0·38;P = 0·01] and validation cohorts (HR 0·18;P = 0·004). Attaining PR at six months on ibrutinib emerges as an intermediate outcome of interest and should be validated as surrogate for PFS in clinical trials evaluating Bruton tyrosine kinase inhibitors in WM.

Abstract We describe the clinical case of a 62-year-old man with an atypical grade II meningioma, invading bone and scalp, and present a step-by-step video description of a modified technique for cranioplasty and scalp reconstruction with latissimus dorsi flap. By using this technique, we aim to minimize the space between the dura and the flap, which would decrease the risk of fluid collections and infections.

Introduction Much attention has been focused on decreasing chronic obstructive pulmonary disease (COPD) hospital readmissions. The US health system has struggled to meet this goal. The objective of this study was to assess the efficacy of telehealth services on the reduction of hospital readmission and mortality rates for COPD. Methods We used a cross-sectional design to examine the association between hospital risk-adjusted readmission and mortality rates for COPD and hospital use of post-discharge telemonitoring (TM). Data for 777 hospitals were sourced from the Centers for Medicare & Medicaid Services and the American Hospital Association annual surveys. Propensity score matching using the kennel weights method was applied to calculate the weighted probability of being a hospital that offers post-discharge TM services. Results Hospitals with post-discharge TM had about 34% significantly higher odds (adjusted odds ratio (AOR) = 1.34; 95% confidence interval (CI) 1.06–1.70) of 30-day COPD readmission and 33% significantly lower odds (AOR = 0.67; 95% CI 0.50–0.90) of 30-day COPD mortality compared to hospitals without post-discharge TM services. Discussion Overall, hospitals that offer post-discharge TM services have seen an improvement in 30-day COPD mortality rates. However, those same hospitals have also experienced a significant increase in 30-day COPD readmissions. TM can potentially decrease mortality in patients recently admitted for acute exacerbation of COPD. The results provide further evidence that readmissions present a problematic assessment of health-care quality, as the need for readmission may or may not be directly related to the quality of care received while in hospital.

Abstract Background Patients with human papillomavirus–related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation–related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.

Abstract Background Artificial intelligence (AI) research in colonoscopy is progressing rapidly but widespread clinical implementation is not yet a reality. We aimed to identify the top implementation research priorities. Methods An established modified Delphi approach for research priority setting was used. Fifteen international experts, including endoscopists and translational computer scientists/engineers, from nine countries participated in an online survey over 9 months. Questions related to AI implementation in colonoscopy were generated as a long-list in the first round, and then scored in two subsequent rounds to identify the top 10 research questions. Results The top 10 ranked questions were categorized into five themes. Theme 1: clinical trial design/end points (4 questions), related to optimum trial designs for polyp detection and characterization, determining the optimal end points for evaluation of AI, and demonstrating impact on interval cancer rates. Theme 2: technological developments (3 questions), including improving detection of more challenging and advanced lesions, reduction of false-positive rates, and minimizing latency. Theme 3: clinical adoption/integration (1 question), concerning the effective combination of detection and characterization into one workflow. Theme 4: data access/annotation (1 question), concerning more efficient or automated data annotation methods to reduce the burden on human experts. Theme 5: regulatory approval (1 question), related to making regulatory approval processes more efficient. Conclusions This is the first reported international research priority setting exercise for AI in colonoscopy. The study findings should be used as a framework to guide future research with key stakeholders to accelerate the clinical implementation of AI in endoscopy.

Abstract: Coronavirus disease 2019 (COVID-19) first emerged in a group of patients who presented with severe pneumonia in Wuhan, China, in December 2019. A novel virus, now called SARSCoV- 2 (Severe Acute Respiratory Syndrome Coronavirus-2), was isolated from lower respiratory tract samples. The current outbreak of infection has spread to over 100 countries and killed more than 340,000 people as of 25th May, 2020. The predominant clinical manifestation of COVID-19 is a respiratory disease- ranging from mild flu-like symptoms to fulminant pneumonia and Acute Respiratory Distress Syndrome (ARDS). Patients with pre-existing cardiovascular risk factors are considered more susceptible to the virus, and these conditions are often worsened by the infection. Furthermore, COVID-19 infection has led to de novo cardiac complications, like acute myocardial injury and arrhythmias. In this review, we have focused on the cardiovascular manifestations of COVID-19 infection that have been reported in the literature so far. We have also outlined the effect of pre-existing cardiovascular disease as well as risk factors on the clinical course and outcomes of COVID-19 infection.

Background: Plasmablastic lymphoma (PBL) is a rare subtype of Non-Hodgkin Lymphoma with a well-known association with HIV infection. The outcomes of PBL patients are typically described with high relapse rates and poor prognosis. (Loghavi S, J Hematol Oncol. 2015; Morscio J, Am J of Pathol. 2014; Castillo JJ, Clin Lymphoma Myeloma Leuk. 2011; Castillo JJ, Am J Hematol. 2008) There has been a paucity of data suggesting that limited stage disease (Ann Arbor stage I-II) may have a more favorable prognosis. However, due to the rarity of this disease there have been no large-scale reviews to confirm this. Thus, many patients with limited stage disease are subject to the aggressive therapy recommendations based on the poor outcomes of PBL patients as a whole. (Loghavi S, J Hematol Oncol. 2015; NCCN Guidelines, version 2.2020; Al-Malki MM, BBMT. 2014) We attempted to determine the treatment patterns and outcomes of patients with limited stage PBL. Methods: We conducted a multi-center (13 US academic centers) retrospective study of patients with limited stage (Ann Arbor stage I-II) Plasmablastic lymphoma. Determination of limited stage and diagnosis of PBL was determined by the investigators at each individual center. Patients diagnosed between 1/1/1990 and 6/1/2018 were included. Baseline demographic, clinical, laboratory, pathology, and outcomes data were extracted by retrospective chart review. Kaplan Meier was utilized for time to event analysis. Results: Baseline characteristics are included in table 1. A total of 80 patients were identified with limited stage disease. With a median follow up of 34 months the 3-yr Progression free survival (PFS) and overall survival (OS) was 71.9% and 78.7% respectively (Figure 1A and 1B). Patients that received frontline chemotherapy with (n=29) and without RT (n=36) had a 3-yr PFS and OS of 84.6% and 96.2% as compared to 64.5% and 70.8%, respectively (Figure 2A and 2B; Figure 3A and 3B). The Hazard ratio (HR) for PFS and OS for chemo (reference) vs chemo-RT was 0.47 (95% CI 0.18-1.3; P=0.131) and 0.18 (95% CI 0.04-0.84; p=0.029) respectively. The HR for PFS and OS for CHOP (n=14, reference) vs EPOCH (n=33) based regimens was 0.37 (95% CI 0.11-1.2; p=0.106) and 0.36 (95% CI 0.079-1.6; p=0.182) respectively. Patients with stage I/IE disease (n=56) had a 3-yr PFS and OS of 73.1% and 81.2% respectively. Patients with stage II/IIE disease (n=24) had a 3-yr PFS and OS of 69.3% and 73.4% respectively. Patients that received aggressive treatment (n=17) with Hyper-CVAD based regimens and/or Auto-SCT as consolidation had a 3-yr PFS and OS of 63.6% and 72.7% respectively. Patients with concomitant HIV (n=16) had a 3-yr PFS and OS of 80.8% and 77.4% respectively. Seven patients received RT alone and 6 patients had surgical resection alone as frontline therapy; 1 patient received no therapy; 1 patient received HAART therapy only and remains in CR without any other treatment for PBL 29 months after diagnosis. There were 8 deaths (10%) related to PBL, 3 deaths (4%) related to treatment of PBL (2 during frontline chemo and 1 upon relapse with salvage chemo), and 9 deaths (11%) related to other causes. The 3-yr lymphoma free survival (LFS) of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (without including treatment related mortality (TRM) as an event) was 89.1%, 85.2%, and 100% respectively. The 3-yr LFS survival of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (including TRM as an event) was 85.1%, 80.0%, and 96.2% respectively. Discussion: Here we report the largest review to our knowledge of limited stage PBL. Outcomes appear to be excellent with 3-yr PFS and OS of 71.9% and 78.7% respectively and a 3-yr LFS of 89.1% (85.1% when attributing TRM as an event). There was no obvious benefit to receiving aggressive therapy with H-CVAD based regimens and/or Auto-SCT. Although this is a small, uncontrolled sample size the HR for OS was improved in patients receiving frontline chemo-RT vs chemo alone 0.18 (95% CI 0.04-0.84; p=0.029). However, this did not take into account TRM with or progression while receiving frontline chemotherapy. Patients who were HIV+ had similar PFS and OS outcomes compared to the entire cohort. This retrospective study clearly demonstrates the favorable outcomes in this patient population, especially in those able to receive definitive therapy for their disease. Disclosures Hess: ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel:Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Nektar: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding. Nowakowski:Nanostrings: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Kymera: Consultancy; Denovo: Consultancy; Kite: Consultancy; Celgene/BMS: Consultancy, Research Funding; Roche: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding. Chavez:Bayer: Consultancy; AbbVie: Consultancy; BeiGene: Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Merck: Research Funding; AstraZeneca: Speakers Bureau; Celgene: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Karyopharm: Consultancy; Verastem: Consultancy; Pfizer: Consultancy. Hill:Beigene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Maddocks:Pharmacyclics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding. Wagner-Johnston:ADC Therapeutics, Regeneron, CALIB-R, Verastem: Membership on an entity's Board of Directors or advisory committees. Kahl:AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy. Alderuccio:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member; Oncinfo: Honoraria; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Puma Biotechnology: Other: Family member; OncLive: Honoraria. Lossos:Janssen Biotech: Honoraria; Verastem: Consultancy, Honoraria; Janssen Scientific: Consultancy, Other; Seattle Genetics: Consultancy, Other; Stanford University: Patents & Royalties; NCI: Research Funding. Portell:Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding. Landsburg:Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Takeda: Research Funding; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau. Castillo:TG Therapeutics: Research Funding; Beigene: Consultancy, Research Funding; Kymera: Consultancy; Janssen: Consultancy, Research Funding; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding.

AbstractBackgroundOur purpose was to explore a case of a complicated ulnar artery pseudoaneurysm and propose an algorithm to guide physicians in this scenario. We present a case of a 5‐year‐old boy with a pediatric ulnar artery pseudoaneurysm that developed after a wrist laceration from broken glass 6 weeks after the initial injury. The diagnosis of pseudoaneurysm was missed, and the patient was transferred to our facility in urgent need of resection and repair due to profuse bleeding. An ultrasound confirmed the suspected diagnosis of ulnar artery aneurysm with thrombosis within the vessel. An area of skin necrosis was also present. Upon exploration of the wound, the ulnar artery pseudoaneurysm was identified and resected. The defect measured six millimeters and it was repaired primarily, under the microscope, after the proximal and distal portions were freed by dissection. The patient's incision was well healed at six‐week follow‐up.MethodA systematic literature review of the English literature on ulnar artery aneurysm was conducted on PubMed/Medline, Embase, Cochrane Clinical Answers, and Cochrane Clinical Trials, without timeframe limitations. Finally, we provide an algorithm to assist the decision‐making process in similar scenarios.ConclusionAlthough ulnar artery aneurysm is rare on a pediatric patient, it should be considered in the differential diagnosis each time a patient presents with a wrist mass. In such cases, a high index of suspicion warrants examination by a hand specialist.