Citations

Abstract Immune checkpoint inhibitors such as ipilimumab and targeted BRAF inhibitors have dramatically altered the landscape of melanoma therapeutics over the past few years. Agents targeting the programmed cell death-1/ligand (PD-1/PD-L1) axis are now being developed and seem to be highly active clinically with favorable toxicity profiles. We report on two patients with BRAF V600E–mutant melanoma who were treated with anti-PD-1 agents as first-line therapy without significant toxicity, followed by vemurafenib at disease progression. Both patients developed severe hypersensitivity drug eruptions with multiorgan injury early in their BRAF inhibitor treatment course. One patient subsequently developed acute inflammatory demyelinating polyneuropathy, and the other developed anaphylaxis upon low-dose vemurafenib rechallenge. Further investigation of the immune response during combination or sequences of melanoma therapeutics is warranted. Furthermore, clinicians should maintain a high index of suspicion for these toxicities when vemurafenib is administered following an anti-PD-1 agent. Cancer Immunol Res; 1(6); 373–7. ©2013 AACR.

AbstractPurposeTo compare the accuracy and reliability of the anatomic and radiographic techniques for identifying the isometric point of the knee.MethodsOnly four specimens were used; however, eight experienced multiligament knee injury surgeons were recruited to address this limitation. Surgeons estimated the isometric point (EIP) on the medial and lateral sides using an anatomic and radiographic method. The x and y coordinates of the EIP were compared to the true isometric point (TIP). T‐tests and interclass correlation coefficients (ICC) were performed to determine the accuracy and reliability between the methods.ResultsThere was no difference in placement of the EIP on the medial side of the knee in the anterior/posterior (x; p = n.s.) and superior/inferior direction (y;p = n.s). The EIP was anterior (p = 0.001) to the TIP with the radiographic method on the lateral side and approached significance (p = 0.05) in the superior/inferior direction. The ICC (95 % CI) for identifying the EIP on the medial side in the anterior/posterior direction using the anatomic method was 0.64 (0.28–0.96) and 0.11 (−0.06 to 0.77) in the superior/inferior direction. Using the radiographic method, the ICC in the anterior/posterior and superior/inferior direction was 0.49 (0.14–0.94) and 0.15 (−0.47 to 0.81), respectively. On the lateral side, the ICC for the anatomic method was 0.84 (0.56–0.99) in the anterior/posterior direction and 0.36 (0.05–0.90) in the superior/inferior direction. Using the radiographic method, the ICC in the anterior/posterior and superior/inferior direction was 0.61 (0.26–0.96) and 0.89 (0.67–0.99), respectively.ConclusionsThere was no difference in accuracy on the medial side of the knee. On the lateral side, the anatomic method was more accurate in the anterior/posterior direction. Reliability was greater in the anterior/posterior direction on both sides of the knee. Surgeons were most likely to place the isometric point anterior and superior to the TIP on both the medial and lateral sides of the knee with either method which has the potential to cause graft lengthening. This should be taken into consideration during reconstruction/repair of the MCL/PMC and LCL/PLC.

Key Points In combination with cyclophosphamide, intravenous busulfan is associated with better leukemia-free and overall survival in AML than TBI.

A novel, hand-held Reference Point Indentation (RPI) instrument, measures how well the bone of living patients and large animals resists indentation. The results presented here are reported in terms of Bone Material Strength, which is a normalized measure of how well the bone resists indentation, and is inversely related to the indentation distance into the bone. We present examples of the instrument's use in: (1) laboratory experiments on bone, including experiments through a layer of soft tissue, (2) three human clinical trials, two ongoing in Barcelona and at the Mayo Clinic, and one completed in Portland, OR, and (3) two ongoing horse clinical trials, one at Purdue University and another at Alamo Pintado Stables in California. The instrument is capable of measuring consistent values when testing through soft tissue such as skin and periosteum, and does so handheld, an improvement over previous Reference Point Indentation instruments. Measurements conducted on horses showed reproducible results when testing the horse through tissue or on bare bone. In the human clinical trials, reasonable and consistent values were obtained, suggesting the Osteoprobe® is capable of measuring Bone Material Strength in vivo, but larger studies are needed to determine the efficacy of the instrument's use in medical diagnosis.