Citations

Background: A feasibility study was conducted to characterize the effects of noncontact low-frequency ultrasound therapy for chronic, recalcitrant lower-leg and foot ulcerations. Methods: The study was an open-label, nonrandomized, baseline-controlled clinical case series. Patients were initially treated with the Mayo Clinic standard of care before the addition of or the switch to noncontact low-frequency ultrasound therapy. We analyzed the medical records of 51 patients (median ± SD age, 72 ± 15 years) with one or more of the following conditions: diabetes mellitus, neuropathy, limb ischemia, chronic renal insufficiency, venous disease, and inflammatory connective tissue disease. All of the patients had lower-extremity ulcers, 20% had a history of amputation, and 65% had diabetes. Of all the wounds, 63% had a multifactorial etiology, and 65% had associated transcutaneous oximetry levels below 30 mm Hg. Results: The mean ± SD treatment time of wounds during the baseline standard of care control period versus the noncontact low-frequency ultrasound therapy period was 9.8 ± 5.5 weeks versus 5.5 ± 2.8 weeks (P < .0001). Initial and end measurements were recorded, and percent volume reduction of the wound was calculated. The mean ± SD percent volume reduction in the baseline standard of care control period versus the noncontact low-frequency ultrasound therapy period was 37.3% ± 18.6% versus 94.9% ± 9.8% (P < .0001). Conclusions: Using noncontact low-frequency ultrasound improved the rate of healing and closure in recalcitrant lower-extremity ulcerations. (J Am Podiatr Med Assoc 97(2): 95–101, 2007)

Short uncemented humeral stems can preserve humeral bone stock and facilitate revision surgery but may be prone to malalignment or loosening, especially when used in reverse total shoulder replacement (TSR). We undertook a retrospective review of 44 patients with a mean age of 76 years (59 to 92) who underwent primary reverse TSR with a short uncemented humeral stem. There were 29 females. The indications for joint replacement included cuff tear associated arthropathy (33), avascular necrosis (six), post-traumatic arthritis (two), and inflammatory arthritis (three). At a mean follow-up of 27 months (24 to 40), pain was rated as mild or none in 43 shoulders (97.7%). The mean active elevation improved from 54° (sd 20°) to 142° (sd 25°) and the mean active external rotation from 14° (sd 13°) to 45° (sd 9°). The outcome, as assessed by the modified Neer score, was excellent in 27 (61.3%), satisfactory in 15 (34.1%), and unsatisfactory in two shoulders (4.5%). Stems were well-positioned, without evidence of significant valgus or varus malalignment in 42 TSRs (95.5%). There was no radiological evidence of loosening of the humeral stem in any patient; 13 TSRs (29.5%) had evidence of proximal humeral remodelling and scapular notching was noted in three (6.8%). Cite this article: Bone Joint J 2014;96-B:526–9.

Severely comminuted fractures of the metatarsal bones with significant bone and soft-tissue loss have commonly subjected patients to proximal amputation procedures. We describe two patients who experienced high-energy traumatic injuries to their limbs that resulted in significant destruction of their first and second metatarsal bones with overlying soft-tissue trauma not amenable to local coverage. In both cases, a vascularized free fibular osteocutaneous flap was used to reconstruct the metatarsal bone defect and traumatized soft tissues so that a proximal amputation was avoided. At an average of 14 months of follow-up, both patients had recovered well and regained independent ambulation, with one patient being able to play soccer. We show that the free fibular osteoseptocutaneous flap is useful in reconstructing significant metatarsal bone defects and in avoiding amputations in this patient population. The skin component of the flap may be used to fill soft-tissue losses, and the fibula bone may be osteotomized so that more than one ray may be reconstructed. (J Am Podiatr Med Assoc 101(6): 531–536, 2011)

Purpose Liver injury is a serious adverse event leading to permanent discontinuation of lapatinib in affected patients. This study aimed to validate previously associated major histocompatibility complex (MHC) variants as predictors of risk of liver injury by using a large, randomized, placebo-controlled trial of lapatinib in human epidermal growth factor receptor 2–positive, early-stage breast cancer (Tykerb Evaluation After Chemotherapy [TEACH]: Lapatinib Versus Placebo In Women With Early-Stage Breast Cancer). Patients and Methods The frequency of ALT elevation cases was compared among four MHC variants in 1,194 patients randomly assigned to lapatinib. Cumulative ALT elevation time courses during treatment were also compared between carriers and noncarriers of specified MHC variants. Results In lapatinib-treated patients, there was a significant difference in ALT case incidence between HLA carriers and noncarriers. The highly correlated alleles HLA-DRB1*07:01 and HLA-DQA1*02:01 (study frequency, 22.4%) were associated with ALT elevation (odds ratio, 14) between cases (n = 37) and controls (n = 1,071). These associations strengthened at higher ALT elevation thresholds and in Hy's Law cases. In lapatinib-treated patients, the overall risk for National Cancer Institute-Common Terminology Criteria for Adverse Events grade 3 ALT elevation (> 5× upper limit of normal) was 2.1%; HLA allele carriers had an increased risk of 7.7%; in noncarriers, risk was reduced to 0.5%, comparable to ALT elevation for all patients receiving placebo. The increase in ALT case incidence in the lapatinib arm showed no evidence of plateau during 1 year of lapatinib treatment. Conclusion These results validate HLA-DRB1*07:01 allele carriage as a predictor of increased risk of lapatinib-induced liver injury and implicate an immune pathology. The HLA association could support clinical management of patients experiencing hepatotoxicity during lapatinib treatment.

During his lifetime and a career spanning 42 years, James Watson Kernohan made numerous contributions to neuropathology, neurology, and neurosurgery. One of these, the phenomenon of ipsilateral, false localizing signs caused by compression of the contralateral cerebral peduncle against the tentorial edge, has widely become known as “Kernohan's notch” and continues to bear his name. The other is a grading system for gliomas from a neurosurgical viewpoint that continues to be relevant for grading of glial tumors 60 years after its introduction. In this paper, the authors analyze these two major contributions in detail within the context of Kernohan's career and explore how they contributed to the development of neurosurgical procedures.

The surgical treatment of meningiomas located at the base of the anterior cranial fossa is often challenging, and the evolution of the surgical strategy to resect these tumors parallels the development of craniotomy, and neurosurgery in general, over the past century. Early successful operations to treat these tumors were pioneered by prominent figures such as Sir William Macewen and Francesco Durante. Following these early reports, Harvey Cushing made significant contributions, allowing a better understanding and treatment of meningiomas in general, but particularly those involving the anterior cranial base. Initially, large-sized unilateral or bilateral craniotomies were necessary to approach these deep-seated lesions. Technical advances such as the introduction of electrosurgery, the operating microscope, and refined microsurgical instruments allowed neurosurgeons to perform less invasive surgical procedures with better results. Today, a wide variety of surgical strategies, including endoscopic surgery and radiosurgery, are used to treat these tumors. In this review, the authors trace the evolution of craniotomy for anterior cranial fossa meningiomas.

Background— Little is known about the clinical value of stress imaging studies in asymptomatic patients after percutaneous coronary intervention (PCI). Methods and Results— Residents of Olmsted County, MN, who underwent PCI were followed up for the occurrence of stress imaging (stress nuclear or stress echocardiography), coronary angiography, or coronary artery bypass grafting (without angiography) as initial procedures after PCI. Patients whose first follow-up procedure was a stress imaging test were evaluated for their symptom status at the time of the study and whether they underwent angiography or revascularization (PCI or coronary artery bypass grafting) within 90 days. Of 1848 patients who underwent PCI during the study period, 710 (38%) had stress imaging as their initial procedure after PCI, and 241 (13% of the entire cohort) were asymptomatic at the time of testing. The majority (86%) of these 241 patients underwent PCI for acute myocardial infarction or unstable angina. Within 90 days of stress imaging, 16 of the 241 asymptomatic patients underwent angiography, and 2 patients were revascularized. Stratified by timing after PCI, none of 138 asymptomatic patients tested within 2 years of PCI underwent revascularization. Two of 103 asymptomatic patients tested after 2 years from PCI underwent revascularization. Compared with patients who were asymptomatic at the time of stress imaging, patients who did not undergo any follow-up procedures (stress imaging, angiography, or coronary artery bypass grafting) after the index PCI were older, were more likely to have comorbidities, and had significantly greater all-cause mortality ( P <0.001). Conclusions— In a population-based sample of patients undergoing PCI primarily for acute coronary syndromes, 1 in 8 had subsequent stress imaging when they were asymptomatic. These stress imaging tests resulted in further revascularization in <1% of patients. The low rate of downstream revascularization suggests that stress imaging in asymptomatic patients after PCI has low value.

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 &lt; 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 &lt; 0.0001), proximal tumor site (P &lt; 0.0001), low grade, age, and sex, whereas codon 13 mutations were associated with proximal site (P &lt; 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: Approximately one-third of those with pediatric-onset multiple sclerosis (MS) experience cognitive impairment. Less is known concerning their change in cognitive functioning over time. Objective: Changes in cognitive function over time were measured in the largest pediatric cohort to date through the US Network of Pediatric MS Centers. Methods: A total of 67 individuals with pediatric MS ( n=62) or clinically isolated syndrome (CIS, n=5), ranging from 8–17 years of age (mean age±standard deviation (SD)=14.37±2.02) completed initial and follow-up neuropsychological testing after an average of 1.64±0.63 years apart. The nine tests administered measure general intellect, attention and working memory, verbal memory, visuomotor integration, language, and executive functioning. Results: Rate of impairment (having one-third or more scores in the impaired range) was 37% at baseline and 33% at follow-up. Tests commonly impaired were measures of visuomotor integration, speeded processing, and attention. Most tested did not decline over two years. There was no clear pattern of change on any specific measure. Conclusion: Findings suggest that, over short timeframes, stable or even improved performances on measures of cognitive ability can occur. Pediatric MS may instead prevent expected age-related cognitive gains.