Citations

Objective The objective of this study is to determine the association of proliferation indices and pathologic biomarkers on overall and recurrence/metastasis‐free survival (OS and RMFS) in patients with sinonasal mucosal melanoma (SNMM) and to assess the genetic mutational landscape of SNMM. Methods This is a retrospective cohort study of 45 SNMM patients without neoadjuvant therapy who underwent surgical therapy with curative intent and had tumor tissue available for histopathologic review, molecular analysis, and genetic mutational assessment. The OS and RMFS were assessed for associations with numerous tumor and patient‐related factors. Results Among proliferative indices, higher Ki67 and mitotic rates were associated with worsened OS and RMFS (Ki67: p = 0.0007 and p < 0.0001; mitotic rate: p = 0.005 and p = 0.0009, respectively). The presence of brisk tumor‐infiltrating lymphocytes (TILs) was associated with improved RMFS ( p = 0.007) and the presence of lymphovascular invasion was associated with worsened OS and RMFS ( p = 0.02 and p = 0.04, respectively). Patients with amelanotic tumors were more likely to have higher T‐stage ( p = 0.046), less likely to have brisk TILs ( p = 0.02) and had worsened RMFS ( p = 0.03). Patients on immunotherapy with tumor Ki67 < 40% had better 3‐year OS compared to those with higher Ki67 index ( p = 0.004). Actionable genetic mutations such as BRAF V600E are rare and present in only 1 of 20 patients tested. Conclusion In SNMM patients, pathologic and proliferation markers such as Ki67, mitotic rate and brisk TILs are associated with survival and may be considered in future staging systems. Clinical response to immunotherapy appears to correlate with the Ki67 index. Given the distinct genetic profile of SNMM, targeted therapies against the MAPK kinase pathway have limited utility. Level of Evidence 3 Laryngoscope , 132:2350–2358, 2022

AbstractBackgroundPoromas, and their malignant counterparts, porocarcinomas, harbor recurrent translocations involving YAP1‐MAML2, YAP1‐NUTM1, and infrequently WWTR1‐NUTM1; YAP1‐NUTM1 being the most common in porocarcinomas. NUT immunohistochemistry (IHC) can be used to identify NUTM1‐translocated tumors. This study sought to investigate potential novel NUTM1‐fusion partners among NUT IHC‐positive poromas and porocarcinomas.MethodsThirteen NUT IHC‐positive poroid tumors (four poromas and nine porocarcinomas) were identified within a multi‐institutional international cohort. Next‐generation sequencing (NGS) assessed for NUTM1 fusion partners.ResultsNGS detected a NUTM1 fusion in 12 of 13 cases: YAP1‐NUTM1 (11/12 cases) and WWTR1‐NUTM1 (1/12 cases). Two of the cases (2/12) with NUTM1 fusion were not called by the NGS algorithm but had at least one read‐spanning YAP1‐NUTM1 break point upon manual review. A NUTM1 fusion was not identified in one case; however, the sample had low RNA quality. The following fusion events were identified: YAP1 exon 4::NUTM1 exon 3 in six cases, YAP1 exon 6::NUTM1 exon 2 in one case, YAP1 exon 3::NUTM1 exon 3 in three cases, WWTR1 exon 3::NUTM1 exon 3 in one case, and YAP1 exon 8::NUTM1 exon 3 fusion in one case.ConclusionWhile no novel NUTM1 fusion partners were identified within our cohort, 12 of 13 cases had discoverable NUTM1 fusions; YAP1‐NUTM1 fusion was detected in 11 cases (92%) and WWTR1‐NUTM1 in 1 case (8%). These data corroborate findings from other recent investigations and further substantiate the utility of NUT IHC in diagnosing a subset of poroid neoplasms. In addition, two of our cases harbored fusions of YAP1 exon 6 to NUTM1 exon 3 and YAP1 exon 8 to NUTM1 exon 2, which have not been reported before in poroid neoplasms and indicate novel break points of YAP1.

Abstract Aims Electrocardiogram (ECG)-enabled stethoscope (ECG-Scope) acquires a single-lead ECGs during cardiac auscultation and may facilitate real-time screening for pathologies not routinely identified by cardiac auscultation alone. We previously demonstrated an artificial intelligence (AI) algorithm can identify left ventricular dysfunction (LVSD) [defined as ejection fraction (EF) ≤ 40%] with an area under the curve (AUC) of 0.91 using a 12-lead ECG. Methods and results One hundred patients referred for clinically indicated echocardiography were prospectively recruited. ECG-Scope recordings with the patient supine and sitting were obtained in multiple electrode locations at the time of the echocardiogram. The AI algorithm for the detection of LVSD was retrained using single leads from ECG-12 and validated against ECG-Scope to determine accuracy for low EF detection (≤35%, &lt;40%, or &lt;50%). We evaluated the algorithm with respect to body position and lead location. Amongst 100 patients (aged 61.3 ± 13.8; 61% male, BMI: 30.0 ± 5.4), eight had EF≤40%, and six had EF 40–50%. The best single recording position was V2 with the patient supine [AUC: 0.88 (CI: 0.80–0.97) for EF≤35%, 0.85 (CI: 0.75–0.95) for EF≤40%, and 0.81 (CI: 0.71–0.90) for EF &lt; 50%]. When using an AI model to select the recording automatically, AUC was 0.91 (CI: 0.84–0.97) for EF≤35%, 0.89 (CI: 0.83–0.96) for EF≤40%, and 0.84 (CI: 0.73–0.94) for EF &lt; 50%. Conclusion An AI algorithm applied to an ECG-enabled stethoscope recording in standard auscultation positions reliably detected the presence of a low EF in this prospective study of patients referred for echocardiography. The ability to screen patients with a possible low EF during routine physical examination may facilitate rapid detection of LVSD.

Background: Haemorrhagic demyelinating lesions are rare, and little is known about the demyelinating diseases with which they are associated, or how lesional haemorrhage affects treatment and outcomes. Objective: To examine the clinical characteristics and outcomes of patients with demyelinating lesions and magnetic resonance imaging (MRI) evidence of haemorrhage seen at the Mayo clinic between 1990 and 2018. Methods: The Mayo Clinic’s medical-record diagnostic-linkage system was used to identify patients with CNS demyelinating disease and parenchymal haemorrhage on brain MRI cross-referenced against a database of patients with pathologically confirmed CNS demyelinating disease. The clinical characteristics, diagnosis, MRI findings, brain histopathology, and outcomes of these patients were reviewed. Results: Ten patients with haemorrhagic demyelination were identified, including three patients who underwent a brain biopsy. The main findings were that haemorrhagic demyelinating lesions most often occur in atypical forms of demyelination, especially acute haemorrhagic leukoencephalitis (AHL, or Weston–Hurst disease) and tumefactive demyelination, and rarely in multiple sclerosis. A spectrum of outcomes was observed for these patients ranging from complete remission through to high level disability. Conclusion: Lesional haemorrhage is uncommon in demyelinating disease where it is most closely associated with AHL. Bleeding within a demyelinating lesion does not always herald a poor prognosis.

Abstract Ewing sarcoma is the second most common primary bone tumor in children. Typical Ewing sarcoma most frequently occurs in long bones and within the pelvis. ALES (adamantinoma-like Ewing sarcoma) is a rare subtype of Ewing sarcoma that is characterized by epithelial differentiation in addition to small round blue cells. Unlike typical Ewing sarcoma, ALES has been described in several cases in the head and neck. Herein, we describe a case of a 9-year-old boy with ALES of the mandible evaluated on 18F-FDG PET/CT with correlative MRI scans.

Abstract Background: Chronic non-specific low back pain (CNLBP) is a common complaint about medical care and carries a heavy social burden. The efficacy of Tuina (TN) or physiotherapy (PT) for CNLBP has been evaluated in previous systematic reviews. However, there is no high-quality evidence to support the efficacy of Tuina. Therefore, this study aims to conduct a large-scale, multicenter, high-quality clinical trial to provide evidence for Tuina to treat CNLBP. Methods: This is a multicenter, assessor-, and analyst-blinded, randomized controlled trial with 3 parallel arms: TN, PT, and TN combined with PT (Tuina combined with physiotherapy) group. Six hundred twelve eligible CNLBP patients will be randomly assigned to the groups in a 1:1:1 ratio in 3 centers. The TN intervention includes 9-step routine techniques, while the PT intervention includes a physiotherapy treatment plan based on a patient's symptoms. The interventions for both groups will last for 30 minutes and will be carried out for 6 sessions in 8 weeks. The primary outcome will be the visual analog scale pain score. And the secondary outcomes will include the Oswestry Disability Index, spinal range of motion, 36-item short-form health survey. Safety evaluation will be recorded during the whole study. All data in this randomized controlled trial will be analyzed by SAS 9.4. Discussion: The results of this trial will provide evidence to evaluate the efficacy of Tuina's value as a treatment for CNLBP. Trial registration: Chinese Clinical Trial Registry (ChiCTR2000040288, November 27, 2020).