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Sorafenib is a small molecule inhibitor of RAF kinase, VEGFR-2, c-KIT, and FLT3. In this randomized phase I study, eligible patients had relapsed/refractory acute myeloid leukemia (AML), and one prior induction regimen, or were age >65 with untreated myelodysplastic syndrome (MDS) or secondary AML. Sorafenib was given orally for 28 days (cont) or 14 days (int) every 4 weeks at three dose levels (100, 200, and 400 mg BID); 300 mg cont was also tested. Forty-two patients were enrolled (median age 71 [37-82]; prior chemotherapy: 22). Dose-limiting toxicity (DLT) was: 100 mg BID: 0/7 patients; 200 mg BID: 2/12 patients; 400 mg BID: 1/17 patients. Sorafenib 400 mg cont was not tolerated in this population: 6/8 received <14 days of treatment due to toxicity; no DLT was seen with 300 mg cont. One CR was seen in a patient with AML with FLT3-ITD. Flow cytometry studies suggest that sorafenib inhibits ERK phosphorylation via c-KIT. The recommended phase II dose in AML is 300 mg BID continuously, and testing in combination and in FLT3-ITD AML is warranted.

Background:The number of systematic reviews and meta-analyses published on the rotator cuff (RC) has increased markedly.Purpose:To quantify the number of systematic reviews and meta-analyses published on the RC and to provide a qualitative summary of the literature.Study Design:Systematic review; Level of evidence, 4.Methods:A systematic search for all systematic reviews and meta-analyses pertaining to the RC published between January 2007 and September 2017 was performed with PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews. Narrative reviews and non–English language articles were excluded.Results:A total of 1078 articles were found, of which 196 met the inclusion criteria. Included articles were summarized and divided into 15 topics: anatomy and function, histology and genetics, diagnosis, epidemiology, athletes, nonoperative versus operative treatment, surgical repair methods, concomitant conditions and surgical procedures, RC tears after total shoulder arthroplasty, biological augmentation, postoperative rehabilitation, outcomes and complications, patient-reported outcome measures, cost-effectiveness of RC repair, and quality of randomized controlled trials.Conclusion:A qualitative summary of the systematic reviews and meta-analyses published on the RC can provide surgeons with a single source of the most current literature.

Background: A large number of systematic reviews and meta-analyses regarding the meniscus have been published. Purpose: To provide a qualitative summary of the published systematic reviews and meta-analyses regarding the meniscus. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic search of all meta-analyses and systematic reviews regarding the meniscus and published between July 2009 and July 2019 was performed with PubMed, CINAHL, EMBASE, and the Cochrane database. Published abstracts, narrative reviews, articles not written in English, commentaries, study protocols, and topics that were not focused on the meniscus were excluded. The most pertinent results were extracted and summarized from each study. Results: A total of 332 articles were found, of which 142 were included. Included articles were summarized and divided into 16 topics: epidemiology, diagnosis, histology, biomechanics, comorbid pathology, animal models, arthroscopic partial meniscectomy (APM), meniscal repair, meniscal root repairs, meniscal allograft transplantation (MAT), meniscal implants and scaffolds, mesenchymal stem cells and growth factors, postoperative rehabilitation, postoperative imaging assessment, patient-reported outcome measures, and cost-effectiveness. The majority of articles focused on APM (20%), MAT (18%), and meniscal repair (17%). Conclusion: This summary of systematic reviews and meta-analyses delivers surgeons a single source of the current evidence regarding the meniscus.

Background: Articular cartilage pathology can result from a spectrum of origins, including trauma, osteochondritis dissecans, avascular necrosis, or degenerative joint disease. Purpose: To compare the differences in clinical and patient-reported outcomes after autologous chondrocyte implantation (ACI) versus osteochondral allograft transplantation (OCA) in patients with focal articular cartilage defects without underlying bone loss. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective review identified patients who underwent ACI or OCA between 2008 and 2016 for isolated grades 3 and 4 articular cartilage defects without underlying bone loss. Outcome measures included the Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), International Knee Documentation Committee (IKDC) evaluation, and 12-Item Short Form Health Survey–Physical Component (SF-12-P) scores. Defect location, size, complications, and rate of subsequent surgery were determined. Results: Overall, 148 patients were included: 82 (55%) underwent ACI and 66 (45%) underwent OCA. The mean age at the time of surgery was 31.2 years within the ACI cohort and 37.7 years within the OCA cohort ( P < .001); the mean follow-up for both cohorts was 6.7 years ( P = .902). Within the ACI group, 28 (34%) patients had multifocal defects, 21 (26%) had defects confined to the femoral condyles, and 33 (40%) had defects in the patellofemoral region. Within the OCA group, 23 (35%) patients had multifocal defects, 30 (46%) had confined femoral condyle lesions, and 13 (20%) had patellofemoral defects. When comparing by lesion location, there were no significant differences in KOOS JR, and IKDC scores between the ACI and OCA cohorts ( P < .05). There was, however, a significant difference for SF-12-P scores for FDD trochlear lesions. In both cohorts, traumatic patellofemoral pathology demonstrated lower patient-reported outcomes and higher failure rates than degenerative lesions. The overall rate of failure, defined as graft failure with revision surgery and/or conversion to arthroplasty, was significantly greater in the OCA group (21% vs 4%; P = .002). Conclusion: Study results indicated that ACI provides similar outcomes to OCA with or without concomitant procedures for the treatment of symptomatic articular cartilage defects in all lesion locations and may have a lower revision rate for multifocal and condylar lesions.

The increasing popularity of citizen science in ecological research has created opportunities for data collection from large teams of observers that are widely dispersed. We established a citizen science program to complement the release of a new variant of the rabbit biological control agent, rabbit haemorrhagic disease virus (RHDV), known colloquially as K5, across Australia. We evaluated the impact of K5 on the national rabbit population and compared citizen science and professionally-collected spotlight count data. Of the citizen science sites (n = 219), 93% indicated a decrease in rabbit abundance following the release of K5. The overall finite monthly growth rate in rabbit abundance was estimated as 0.66 (95%CI, 0.26, 1.03), averaging a monthly reduction of 34% at the citizen science sites one month after the release. No such declines were observed at the professionally monitored sites (n = 22). The citizen science data submissions may have been unconsciously biased or the number of professional sites may have been insufficient to detect a change. Citizen science participation also declined by 56% over the post-release period. Future programs should ensure the use of blinded trials to check for unconscious bias and consider how incentives and/or the good will of the participants can be maintained throughout the program.

Aims Perineural invasion (PNI) by prostatic adenocarcinoma is debated as a prognostic parameter. This study investigates the prognostic predictive value of PNI in a series of patients with locally advanced prostate cancer treated with radiotherapy and androgen deprivation using 10 years outcome data from the TROG 03.04 RADAR trial. Methods Diagnostic prostate biopsies from 976 patients were reviewed and the presence of PNI noted. Patients were followed for 10 years according to the trial protocol or until death. The primary endpoint for the study was time to bone metastasis. Secondary endpoints included time to soft tissue metastasis, transition to castration resistance, prostate cancer‐specific mortality and all‐cause mortality. Results PNI was detected in 449 cases (46%), with 234 cases (24%) having PNI in more than one core. The presence of PNI was significantly associated with higher ISUP grade, clinical T staging category, National Comprehensive Cancer Network risk group, and percent positive biopsy cores. The cumulative probability of bone metastases according to PNI status was significant over the 10 years follow‐up interval of the study (log‐rank test P < 0.0001). PNI was associated with all endpoints on univariable analysis. After adjusting for baseline clinicopathological and treatment factors, bone metastasis was the only endpoint in which PNI retained its prognostic significance (hazard ratio 1.42, 95% confidence interval 1.05–1.92, P = 0.021). Conclusions The association between PNI and the development of bone metastases supports the inclusion of this parameter as a component of the routine histology report. Further this association suggests that evaluation of PNI may assist in selecting those patients who should be monitored more closely during follow‐up.

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