Forty cases of disease of the central nervous system, characterized by several episodes and disseminated lesions, with onset in childhood and clinically typical of multiple sclerosis, were studied. The disease as it occurs in children does not appear to differ clinically from the disease as observed in adults, in respect to mode of onset, symptoms, physical findings, and changes in the spinal fluid. In the Mayo Clinic series, however, almost twice as many girls as boys were affected. A pediatrician confronted with a child showing evidence of scattered neurologic deficits that remit, particularly a disturbance of vision and co-ordination, should consider the possibility of multiple sclerosis.
A 10-month-old boy with circumscribed lobular lipoblastomatosis of the trunk was examined and treated at the Mayo Clinic. This is only the third case of lipoblastomatosis at our institution. The diagnosis depends on the pathologist, and the lesion must be differentiated from low-grade liposarcoma. Effective treatment involves adequate local excision and local reexcision for recurrence.
Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients
Abstract Background: Sorafenib (Sor) remains a first-line option for hepatocellular carcinoma (HCC) or refractory renal cell carcinomas (RCC). PLC/PRF/5 HCC model showed upregulation of hypoxia with enhanced efficacy when Sor is combined with hypoxia-activated prodrug evofosfamide (Evo). Methods: This phase IB 3 + 3 design investigated 3 Evo dose levels (240, 340, 480 mg/m2 on days 8, 15, 22), combined with Sor 200 mg orally twice daily (po bid) on days 1-28 of a 28-day cycle. Primary objectives included determining maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of Sor + Evo. Results: Eighteen patients were enrolled (median age 62.5 years; 17 male /1 female; 12 HCC/6 RCC) across three dose levels (DL0: Sor 200 mg bid/Evo 240 mg/m2 [n=6], DL1:Sor 200 mg bid/Evo 480 mg/m2 [n=5], DL1a: Sor 200 mg bid/Evo 340 mg/m2 [n=7]). Two dose-limiting toxicities (DLTs) were reported with Evo 480 mg/m2 (grade 3 mucositis, grade 4 hepatic failure). Grade 3 rash DLT was observed in one patient at Evo 240 mg/m2. No DLTs were observed at Evo 340 mg/m2. MTD and RP2D were established as Sor 200 mg/Evo 340 mg/m2 and Sor 200/Evo 240 mg/m2, respectively. The most common treatment-related adverse events included fatigue, hand-foot syndrome, hypertension, and nausea/vomiting. Two partial responses were observed, one each at DL0 and DL1a.; disease control rate was 55%.Conclusions: RP2D was established as sorafenib 200 mg bid + Evo 240 mg/m2. While preliminary anti-tumor activity was observed, future development must account for advances in immunotherapy in HCC/RCC. NCT01497444Date of registration December 20, 2011
Identifying Malignant Lymph Nodes of Prostate Cancer Patients Using A Combination of Pre-Trained Deep Models and Traditional Machine Learning Classifiers
Abstract Prostate cancer is the second most common new cancer diagnosis in the United States. The prostate gland sits beneath the urinary bladder and surrounds the first part of the urethra. Usually, prostate cancer is slow-growing; stays confined to the prostate gland; and can be treated conservatively (active surveillance) or with surgery. However, if the cancer has spread beyond the prostate, such as to the lymph nodes, then that suggests the cancer is more aggressive and surgery is not adequate. In those cases, radiation and/or systemic therapies (e.g., chemotherapy, immunotherapy) are required. The challenge is that it is often difficult for radiologists to differentiate malignant lymph nodes from non-malignant ones with current medical imaging technology. In this study, we design a scalable hybrid approach utilizing a deep learning model to extract features into a machine learning classifier to automatically identify malignant lymph nodes in patients with prostate cancer.
Multicenter Study of Long-Term Safety of Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease
Background and objectives Tolvaptan slows kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. In the 3-year Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4, 2-year extension to TEMPO 3:4 (TEMPO 4:4), and 1-year Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trials, aquaretic adverse events were common. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations occurred in all three studies. Three patients met Hy Law criteria (ALT or AST more than three times and total bilirubin more than two times the upper limit of normal) for severe drug-induced liver injury (two in TEMPO 3:4 and one in TEMPO 4:4). In REPRISE, liver enzyme monitoring frequency was increased to monthly, with no Hy Law cases. A long-term, phase 3 safety study has further characterized tolvaptan safety. Design, setting, participants, & measurements Subjects who completed TEMPO 4:4, REPRISE, or other tolvaptan trials could enroll in this prospective, multinational, open-label safety study. Assessments included monthly liver enzyme testing during the first 18 months of tolvaptan exposure and every 3 months thereafter. Results Among 1803 subjects, median tolvaptan exposure during the extension was 651 days (interquartile range, 538–924), and cumulative exposure (extension and previous trials) was ≤11 years. Subjects entering from REPRISE placebo experienced more aquaretic adverse events compared with subjects from TEMPO 4:4 or REPRISE tolvaptan ( i.e ., patients with prior long-term tolvaptan exposure). Liver enzyme elevations also occurred more frequently in subjects from REPRISE placebo. Percentages experiencing ALT ≥3/≥5/ ≥10/≥20 times the upper limit of normal were 3.2%/2.1%/0.9%/0.7%, respectively, in subjects from REPRISE placebo and 0.6%–1.1%/0.0%–0.1%/0%/0%, respectively, in those from REPRISE tolvaptan and TEMPO 4:4. Percentages experiencing AST ≥3/ ≥5/≥10/≥20 times the upper limit of normal were 6.9%/3.8%/2.3%/0.8%, respectively, in subjects from REPRISE placebo and 0.9%–2.0%/0.0%–1.0%/0%/0%, respectively, in those from REPRISE tolvaptan and TEMPO 4:4. No Hy Law cases occurred. Conclusions No new safety signals emerged during this long-term extension. Monthly liver function testing for the first 18 months of treatment appeared to enable effective detection and management of transaminase elevations. Clinical Trial registry name and registration number: Open Label Extension of TEMPO 3:4, NCT02251275
Bronchial Rheoplasty Treatment for Chronic Bronchitis Using the Rheox System: 12-Month Results of a Prospective, Multi-Center Study
Abstract Rationale Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium. Objectives To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB. Methods Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George’s Respiratory Questionnaire (SGRQ). Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, −7.9; median, −8.0; P = 0.0002) and SGRQ (mean, −14.6; median, −7.2; P = 0.0002) scores were observed, with similar observations through 12 months. Conclusions This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB. Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT 03107494).
Deep Learning Based on MRI for Differentiation of Low‐ and High‐Grade in Low‐Stage Renal Cell Carcinoma
BackgroundPretreatment determination of renal cell carcinoma aggressiveness may help to guide clinical decision‐making.PurposeTo evaluate the efficacy of residual convolutional neural network using routine MRI in differentiating low‐grade (grade I–II) from high‐grade (grade III–IV) in stage I and II renal cell carcinoma.Study TypeRetrospective.PopulationIn all, 376 patients with 430 renal cell carcinoma lesions from 2008–2019 in a multicenter cohort were acquired. The 353 Fuhrman‐graded renal cell carcinomas were divided into a training, validation, and test set with a 7:2:1 split. The 77 WHO/ISUP graded renal cell carcinomas were used as a separate WHO/ISUP test set.Field Strength/Sequence1.5T and 3.0T/T2‐weighted and T1 contrast‐enhanced sequences.AssessmentThe accuracy, sensitivity, and specificity of the final model were assessed. The receiver operating characteristic (ROC) curve and precision‐recall curve were plotted to measure the performance of the binary classifier. A confusion matrix was drawn to show the true positive, true negative, false positive, and false negative of the model.Statistical TestsMann–Whitney U‐test for continuous data and the chi‐square test or Fisher's exact test for categorical data were used to compare the difference of clinicopathologic characteristics between the low‐ and high‐grade groups. The adjusted Wald method was used to calculate the 95% confidence interval (CI) of accuracy, sensitivity, and specificity.ResultsThe final deep‐learning model achieved a test accuracy of 0.88 (95% CI: 0.73–0.96), sensitivity of 0.89 (95% CI: 0.74–0.96), and specificity of 0.88 (95% CI: 0.73–0.96) in the Fuhrman test set and a test accuracy of 0.83 (95% CI: 0.73–0.90), sensitivity of 0.92 (95% CI: 0.84–0.97), and specificity of 0.78 (95% CI: 0.68–0.86) in the WHO/ISUP test set.Data ConclusionDeep learning can noninvasively predict the histological grade of stage I and II renal cell carcinoma using conventional MRI in a multiinstitutional dataset with high accuracy.Level of Evidence3Technical Efficacy Stage2