Citations

Abstract Purpose: We examined the prognostic impact of specific KRAS mutations in patients with stage III colon adenocarcinoma receiving adjuvant FOLFOX alone or combined with cetuximab in a phase III trial (N0147). Analysis was restricted to BRAF–wild-type tumors, because BRAF mutation was associated with poor prognosis, and BRAF and KRAS mutations are mutually exclusive. Experimental Design: The seven most common KRAS mutations in codon 12 and codon 13 were examined in 2,478 BRAF–wild-type tumors. Because KRAS mutations in codon 12 (n = 779) or 13 (n = 220) were not predictive of adjuvant cetuximab benefit, study arms were pooled for analysis. Disease-free survival (DFS) was evaluated by HRs using Cox models. Results: KRAS mutations in codon 12 (multivariate HR, 1.52; 95% confidence interval, CI, 1.28–1.80; P < 0.0001) or codon 13 (multivariate HR, 1.36; 95% CI, 1.04–1.77; P = 0.0248) were significantly associated with shorter DFS compared with patients with wild-type KRAS/BRAF tumors, independent of covariates. KRAS codon 12 mutations were independently associated with proficient mismatch repair (P < 0.0001), proximal tumor site (P < 0.0001), low grade, age, and sex, whereas codon 13 mutations were associated with proximal site (P < 0.0001). Conclusion: KRAS mutations in either codon 12 or 13 are associated with inferior survival in patients with resected stage III colon cancer. These data highlight the importance of accurate molecular characterization and the significant role of KRAS mutations in both codons in the progression of this malignancy in the adjuvant setting. Clin Cancer Res; 20(11); 3033–43. ©2014 AACR.

Background and Purpose— To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. Methods— After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. Results— Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. Conclusions— Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

Background Cardiovascular implantable electronic device (CIED) pocket infections are often related to recent CIED placement or manipulation, but these infections are not well characterized. The clinical presentation of CIED pocket infection, based on temporal onset related to last CIED procedure, deserves further study. Methods The MEDIC (Multicenter Electrophysiologic Device Infection Cohort) prospectively enrolled subjects with CIED infection. Subjects were stratified into those whose infection occurred <12 months (early) or ≥12 months (late) since their last CIED‐related procedure. Results There were 132 subjects in the early group and 106 in the late group. There were more females (P = 0.009) and anticoagulation use (P = 0.039) in the early group. Subjects with early infections were more likely to have had a generator change or lead addition as their last procedure (P = 0.03) and had more prior CIED procedures (P = 0.023). Early infections were more likely to present with pocket erythema (P < 0.001), swelling (P < 0.001), and pain (P = 0.007). Late infections were more likely to have pocket erosion (P = 0.005) and valvular vegetations (P = 0.009). In bacteremic subjects, early infections were more likely healthcare‐associated (P < 0.001). In‐hospital and 6‐month mortality were equivalent. Conclusion A total of 45% of patients with CIED pocket infection presented >12 months following their last CIED‐related procedure. Patients with early infection were more likely to be female, on anticoagulation, and present with localized inflammation, whereas those with late infection were more likely to have CIED erosion or valvular endocarditis.

Key Points NK cells and their expression of FcRγIII (CD16) are decreased in MDS and inversely correlate with a substantial increase in MDSCs. CD16xCD33 BiKE potently activates blood and marrow MDS-NK cells at all diseases stages to lyse CD33+ MDS and CD33+ MDSC targets.

A significant issue in research on the epidemiology of injury relates not to the numerator (injury), but to the denominator: exposure time. Most hockey injury studies “assume” equivalent playing time. This assumption is not problematic for large investigations designed to establish differences in concussion rates between levels of participation. However, the assumption is a serious issue when investigators are testing differences in rules, coaching programs, skills training, and behavioral interventions. Because players are at higher risk for injuries when fatigued, individual exposure time is important. Until recently, analyzing individual playing times for ice hockey teams has been a daunting task, as it involved the hand-written recording of times using a grid and check marks. During the 2011–2012 season, a computer-based program, Time on Ice (TOI), was used to expedite the accurate recording of individual exposure, including shorthanded and power-play situations. The purpose of using TOI software in this study was to ensure that its results were in agreement with the exposure times recorded manually using a paper-and-pencil grid. Preliminary results from six games (12 records of data) showed that exposure time ranged from 6.3 to 26.4 min when using manual recording and 8.3 to 33.2 min when using TOI. These methods were concluded to be in agreement. Now that software has been developed exclusively for the task of tracking time on ice, it is recommended that exposure time be measured when injuries such as concussion are being evaluated and causation is being determined. The Sport Performance Analyzer TOI system is commercially available.

Catastrophic injuries in the sport of ice hockey are rare but result in life-altering conditions such as paralysis and cognitive impairment, or even death. Potentially catastrophic injuries without permanent functional disability are also a serious concern. In 2006, Mayo Clinic Sports Medicine Center and USA Hockey established a registry for catastrophic and potentially catastrophic injuries sustained by ice hockey players in the Unites States. Since data collection began in 2008, our research team has acquired 45 database entries obtained from self-reports, Google Alerts (using the term “hockey injury”), and the National Electronic Injury Surveillance System. Cervical fracture and neck laceration were the most common types of injuries, with the spine and head being the most commonly injured body parts. Steps to reduce the aforementioned injury types and locations include USA Hockey's “Heads Up, Do Not Duck” program and increased use and awareness of neck laceration protectors.

ObjectiveTo determine the proportion of patients who would have an unsuccessful lumbar puncture (LP) due to commonly used LP needles being too short.MethodsThree hundred consecutive adults (age 16–99, mean age 56) who underwent abdominal CT over a 6‐month period were identified. The distance from the skin to the midpoint of the spinal canal was measured in the axial plane, at the level of the iliac crest. This was compared to the length of commonly used spinal needles (88 mm) to assess the number of patients who would have an unsuccessful LP due to this distance being greater than 88 mm from the skin.ResultsIn 72/300 (24%) patients, the midpoint of the spinal canal was greater than 88 mm from the skin. A total of 54/72 (75%) of those patients were female. Of the female participants, 54/159 (34%) had the midpoint of their spinal canal at a distance of greater than 88 mm from the skin. In the male patients, only 18/141 (13%) had a similar finding.ConclusionThis is the first high‐quality study to demonstrate that 24% of the population will have an unsuccessful LP procedure if commonly available spinal needles. We demonstrated that 34% of female patients would have an unsuccessful procedure while, in contrast, a successful LP should be possible in 87% of male patients.