Citations

Background Cardioversion is common among patients with atrial fibrillation (AF). We hypothesised that novel oral anticoagulants (NOAC) used in clinical practice resulted in similar rates of stroke compared with vitamin K antagonists (VKA) for cardioversion. Methods Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II, patients with AF who had a cardioversion, follow-up data and an AF diagnosis within 6 months of enrolment were identified retrospectively. Clinical outcomes were compared for patients receiving a NOAC or VKA for 1 year following cardioversion. Results Among 13 004 patients with AF, 2260 (17%) underwent cardioversion. 1613 met the inclusion criteria for this analysis. At the time of cardioversion, 283 (17.5%) were receiving a VKA and 1330 (82.5%) a NOAC. A transoesophageal echocardiogram (TOE) was performed in 403 (25%) cardioversions. The incidence of stroke/transient ischaemic attack (TIA) at 30 days was the same for patients having (3.04 per 100 patient-years) or not having (3.04 per 100 patient-years) a TOE (p=0.99). There were no differences in the incidence of death (HR 1.19, 95% CI 0.62 to 2.28, p=0.61), cardiovascular hospitalisation (HR 1.02, 95% CI 0.76 to 1.35, p=0.91), stroke/TIA (HR 1.18, 95% CI 0.30 to 4.74, p=0.81) or bleeding-related hospitalisation (HR 1.29, 95% CI 0.66 to 2.52, p=0.45) at 1 year for patients treated with either a NOAC or VKA. Conclusions Cardioversion was a low-risk procedure for patients treated with NOAC, and there were statistically similar rates of stroke/TIA 30 days after cardioversion as for patients treated with VKA. There were no statically significant differences in death, stroke/TIA or major bleeding at 1 year among patients treated with NOAC compared with VKA after cardioversion.

Abstract Purpose: Clear cell renal cell carcinoma (ccRCC) is frequently associated with inactivation of the von Hippel–Lindau tumor suppressor, resulting in activation of HIF-1α and HIF-2α. The current paradigm, established using mechanistic cell-based studies, supports a tumor promoting role for HIF-2α, and a tumor suppressor role for HIF-1α. However, few studies have comprehensively examined the clinical relevance of this paradigm. Furthermore, the hypoxia-associated factor (HAF), which regulates the HIFs, has not been comprehensively evaluated in ccRCC. Experimental Design: To assess the involvement of HAF/HIFs in ccRCC, we analyzed their relationship to tumor grade/stage/outcome using tissue from 380 patients, and validated these associations using tissue from 72 additional patients and a further 57 patients treated with antiangiogenic therapy for associations with response. Further characterization was performed using single-cell mRNA sequencing (scRNA-seq), RNA-in situ hybridization (RNA-ISH), and IHC. Results: HIF-1α was primarily expressed in tumor-associated macrophages (TAMs), whereas HIF-2α and HAF were expressed primarily in tumor cells. TAM-associated HIF-1α was significantly associated with high tumor grade and increased metastasis and was independently associated with decreased overall survival. Furthermore, elevated TAM HIF-1α was significantly associated with resistance to antiangiogenic therapy. In contrast, high HAF or HIF-2α were associated with low grade, decreased metastasis, and increased overall survival. scRNA-seq, RNA-ISH, and Western blotting confirmed the expression of HIF-1α in M2-polarized CD163-expressing TAMs. Conclusions: These findings highlight a potential role of TAM HIF-1α in ccRCC progression and support the reevaluation of HIF-1α as a therapeutic target and marker of disease progression.

Abstract Background Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett’s esophagus (BE). Interpretation of a 6-cm long, circumferential VLE “full scan” may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE). Methods 29 VLE full scan videos (15 neoplastic and 14 NDBE) were randomly evaluated by 12 VLE experts using a web-based module. Experts were blinded to the endoscopic BE images and histology. The 15 neoplastic cases contained a subtle endoscopically visible lesion, which on endoscopic resection showed high grade dysplasia or cancer. NDBE cases had no visible lesions and an absence of dysplasia in all biopsies. VLE videos were first scored as “neoplastic” or “NDBE.” If neoplastic, assessors located the area most suspicious for neoplasia. Primary outcome was the performance of VLE experts in differentiating between non-dysplastic and neoplastic full scan videos, calculated by accuracy, sensitivity, and specificity. Secondary outcomes included correct location of neoplasia, interobserver agreement, and level of confidence. Results VLE experts correctly labelled 73 % (95 % confidence interval [CI] 67 % – 79 %) of neoplastic VLE videos. In 54 % (range 27 % – 66 %) both neoplastic diagnosis and lesion location were correct. NDBE videos were consistent with endoscopic biopsies in 52 % (95 %CI 46 % – 57 %). Interobserver agreement was fair (kappa 0.28). High level of confidence was associated with a higher rate of correct neoplastic diagnosis (81 %) and lesion location (73 %). Conclusions Identification of subtle neoplastic lesions in VLE full scans by experts was disappointing. Future studies should focus on improving methodologies for reviewing full scans, development of refined VLE criteria for neoplasia, and computer-aided diagnosis of VLE scans.

Abstract Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3–T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.

Objective: To compare the clinical outcomes of static versus dynamic external fixation for elbow fracture-dislocations with persistent instability after surgical management. Design: Comparative, retrospective review. Setting: Two tertiary referral upper-extremity centers. Patients: Twenty-four elbows requiring external fixation for persistent elbow instability within 90 days of surgical management of an elbow fracture-dislocation. Intervention: Static and dynamic external fixation was used in 16 and 8 patients, respectively, for a median of 39 days (interquartile range, 33–48 days). Main Outcome Measurements: Elbow range of motion, complications, and revision surgeries. Results: Immediately after static and dynamic external fixation removal, there was no difference in elbow extension [33 degrees ± 16 degrees vs. 41 degrees ± 13 degrees, mean difference (MD) 7 degrees, 95% confidence interval (CI) −6 degrees–22 degrees] or flexion (114 degrees ± 35 degrees vs. 118 degrees ± 11 degrees, MD 4 degrees, 95% CI -23 degrees–132 degrees), respectively. At last follow-up, static and dynamic external fixation groups had no difference in elbow extension (27 degrees ± 13 degrees vs. 24 degrees ± 10 degrees, MD -3 degrees, 95% CI –15 degrees–7 degrees) or flexion (129 degrees ± 12 degrees vs. 128 degrees ± 14 degrees, MD -1 degree, 95% CI -13 degrees–10 degrees), respectively. Static and dynamic external fixation groups had no difference in complications [7 (44%) vs. 5 (63%), difference 19%, 95% CI -23%–54%] or revision surgeries [6 (38%) vs. 4 (50%), difference 13%, 95% CI -27%–49%]. Conclusions: No difference in range of motion, complications, and revision surgeries was detected after static versus dynamic external fixation of persistently unstable elbow fracture-dislocations. Due to ease of application, static external fixation is our preferred treatment for these injuries. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background. Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. Methods. Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. Results. The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or <72 hours of appropriate antimicrobial therapy in case of ongoing sepsis were considered reasons to delay LT. A simple assessment of the number of organs failing was considered the most appropriate way to decide whether LT should be delayed or denied, with respiratory, circulatory and metabolic failures having the most influence in this decision. The thresholds of severity of organ failures contraindicating LT for which a consensus was achieved were a Pa o 2 /FiO2 ratio<150 mm Hg, a norepinephrine dose >1 μg/kg per minute and a serum lactate level >9 mmol/L. Conclusions. Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented.

Abstract BACKGROUND Facial nerve schwannomas are rare, challenging tumors to manage due to their nerve of origin. Functional outcomes after stereotactic radiosurgery (SRS) are incompletely defined. OBJECTIVE To analyze the effect of facial nerve segment involvement on functional outcome for these tumors. METHODS Patients who underwent single-session SRS for facial nerve schwannomas with at least 3 mo follow-up at 11 participating centers were included. Preoperative and treatment variables were recorded. Outcome measures included radiological tumor response and neurological function. RESULTS A total of 63 patients (34 females) were included in the present study. In total, 75% had preoperative facial weakness. Mean tumor volume and margin dose were 2.0 ± 2.4 cm 3 and 12.2 ± 0.54 Gy, respectively. Mean radiological follow-up was 45.5 ± 38.9 mo. Progression-free survival at 2, 5, and 10 yr was 98.1%, 87.2%, and 87.2%, respectively. The cumulative proportion of patients with regressing tumors at 2, 5, and 10 yr was 43.1%, 63.6%, and 63.6%, respectively. The number of involved facial nerve segments significantly predicted tumor progression ( P = .04). Facial nerve function was stable or improved in 57 patients (90%). Patients with involvement of the labyrinthine segment of the facial nerve were significantly more likely to have an improvement in facial nerve function after SRS ( P = .03). Hearing worsened in at least 6% of patients. Otherwise, adverse radiation effects included facial twitching (3 patients), facial numbness (2 patients), and dizziness (2 patients). CONCLUSION SRS for facial nerve schwannomas is effective and spares facial nerve function in most patients. Some patients may have functional improvement after treatment, particularly if the labyrinthine segment is involved.