Citations

Nerve tubes, guides, or conduits are a promising alternative for autologous nerve graft repair. The first biodegradable empty single lumen or hollow nerve tubes are currently available for clinical use and are being used mostly in the repair of small-diameter nerves with nerve defects of < 3 cm. These nerve tubes are made of different biomaterials using various fabrication techniques. As a result these tubes also differ in physical properties. In addition, several modifications to the common hollow nerve tube (for example, the addition of Schwann cells, growth factors, and internal frameworks) are being investigated that may increase the gap that can be bridged. This combination of chemical, physical, and biological factors has made the design of a nerve conduit into a complex process that demands close collaboration of bioengineers, neuroscientists, and peripheral nerve surgeons. In this article the authors discuss the different steps that are involved in the process of the design of an ideal nerve conduit for peripheral nerve repair.

Intraneural ganglion cysts have been considered a curiosity for 2 centuries. Based on a unifying articular (synovial) theory, recent evidence has provided a logical explanation for their formation and propagation. The fundamental principle is that of a joint origin and a capsular defect through which synovial fluid escapes following the articular branch, typically into the parent nerve. A stereotypical, reproducible appearance has been characterized that suggests a shared pathogenesis. In the present report the authors will provide a mechanistic explanation that can then be mathematically tested using a preliminary model created by finite element analysis.

Object Intraneural ganglia are nonneoplastic mucinous cysts contained within the epineurium of peripheral nerves. Their pathogenesis has been controversial. Historically, the majority of authors have favored de novo formation (degenerative theory). Because of their rarity, intraneural ganglia affecting the upper limb have been misunderstood. This study was designed to critically analyze the literature and to test the hypothesis that intraneural ganglia of the upper limb act analogously to those in the lower limb, being derived from an articular source (synovial theory). Methods Two patients with digital intraneural cysts were included in the study. An extensive literature review of intraneural ganglia of the upper limb was undertaken to provide the historical basis for the study. Results In both cases, the digital intraneural ganglia were demonstrated to have joint connections; the one patient in whom an articular branch was not appreciated initially had evidence on postoperative MR images of persistence of intraneural cyst after simple decompression was performed. Eighty-six cases of intraneural lesions were identified in varied locations of the upper limb: the most common sites were the ulnar nerve at the elbow and wrist, occurring 38 and 22 times, respectively. Joint connections were present in only 20% of the cases published by other groups. Conclusions The authors believe that the fundamental principles of the unifying articular (synovial) theory (that is, articular branch connections, cyst fluid following a path of least resistance, and the role of pressure fluxes) previously described to explain intraneural ganglia in the lower limb apply to those cases in the upper limb. In their opinion, the joint connection is often not identified because of the cysts' rarity, radiologists' and surgeons' inexperience, and the difficulty visualizing and demonstrating it because of the small size of the cysts. Furthermore, they believe that recurrence (subclinical or clinical) is not only underreported but also predictable after simple decompression that fails to address the articular branch. In contrast, intraneural recurrence can be eliminated with disconnection of the articular branch.

Object The results of the International Subarachnoid Aneurysm Trial (ISAT) demonstrated lower rates of death and disability with endovascular treatment (coiling) than with open surgery (clipping) to secure the ruptured intracranial aneurysm. However, cost-effectiveness may not be favorable because of the greater need for follow-up cerebral angiograms and additional follow-up treatment with endovascular methods. In this study, the authors' goal was to compare the cost-effectiveness of endovascular and neurosurgical treatments in patients with ruptured intracranial aneurysms who were eligible to undergo either type of treatment. Methods Clinical data (age, sex, frequency of retreatment, and rebleeding) and quality of life values were obtained from the ISAT. Total cost included those associated with disability, hospitalization, retreatment, and rebleeding. Cost estimates were derived from the Premier Perspective Comparative Database, data from long-term care in stroke patients, and relevant literature. Incremental cost-effectiveness ratios (ICERs) were estimated during a 1-year period. Parametric bootstrapping was used to determine the uncertainty of the estimates. Results The median estimated costs of endovascular and neurosurgical treatments (in US dollars) were $45,493 (95th percentile range $44,693–$46,365) and $41,769 (95th percentile range $41,094–$42,518), respectively. The overall quality-adjusted life years (QALY) in the endovascular group was 0.69, and for the neurosurgical group it was 0.64. The cost per QALY in the endovascular group was $65,424 (95th percentile range $64,178–$66,772), and in the neurosurgical group it was $64,824 (95th percentile range $63,679–$66,086). The median estimated ICER at 1 year for endovascular treatment versus neurosurgical treatment was $72,872 (95th percentile range $50,344–$98,335) per QALY gained. Given that most postprocedure angiograms and additional treatments occurred in the 1st year and the 1-year disability status is unlikely to change in the future, ICER for endovascular treatment will progressively decrease over time. Conclusions Using outcome and economic data obtained in the US at 1 year after the procedure, endovascular treatment is more costly but is associated with better outcomes than the neurosurgical alternative among patients with ruptured intracranial aneurysms who are eligible to undergo either procedure. With accrual of additional years with a better outcome status, the ICER for endovascular coiling would be expected to progressively decrease and eventually reverse.

Background and Purpose— Analyze the relationship between the location and extent of sinus thrombosis and presence and severity of brain lesions. Methods— Retrospective chart and neuroimaging review of patients with documented CVST. A CVST score was devised to quantify the extent of cerebral venous sinus thrombosis. Results— Nineteen of 56 (34%) patients had brain lesions. The extent of sinus thrombus was associated with increased risk of brain lesions (CVST score 1.9 among patients without brain lesions versus 3.1 in those with lesions; P =0.006). Age, sex, and acquired or hereditary thrombophilias were not associated with the risk of parenchymal lesions. Functional outcomes were favorable even in patients with extensive CVST and parenchymal lesions at presentation. Conclusions— The extent of the sinus involvement correlates with the risk of brain lesions in patients with CVST, but additional factors might also contribute to their occurrence.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77 469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)–proteins (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.

Abstract We examined whether monoclonal gammopathy of undetermined significance (MGUS) is increased in first-degree relatives of multiple myeloma (MM) or MGUS patients. Probands were recruited from a population-based prevalence study (MGUS) and the Mayo Clinic (MM). Serum samples were collected from first-degree relatives older than 40 years and subjected to electrophoresis and immunofixation. The prevalence of MGUS in relatives was compared with population-based rates. Nine-hundred eleven relatives of 232 MM and 97 MGUS probands were studied. By electrophoresis, MGUS was detected in 55 (6%) relatives, and immunofixation identified 28 additional relatives for an age- and sex-adjusted prevalence of 8.1% (95% CI, 6.3 to 9.8). The prevalence of MGUS in relatives increased with age (1.9%, 6.9%, 11.6%, 14.6%, 21.0% for ages 40-49, 50-59, 60-69, 70-79, ≥ 80 years, respectively; P < .001). Using similar MGUS detection methods, there was a higher risk of MGUS in relatives (age-adjusted risk ratio [RR], 2.6; 95% CI, 1.9 to 3.4) compared with the reference population. The increased risk was seen among relatives of MM (RR, 2.0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI, 2.1 to 4.8). The increased risk of MGUS in first-degree relatives of MGUS or MM patients implies shared environment and/or genetics.

Abstract Resistance to temozolomide and radiotherapy is a major problem for patients with glioblastoma but may be overcome using the poly(ADP-ribose) polymerase inhibitor ABT-888. Using two primary glioblastoma xenografts, the efficacy of ABT-888 combined with radiotherapy and/or temozolomide was evaluated. Treatment with ABT-888 combined with temozolomide resulted in significant survival prolongation (GBM12: 55.1%, P = 0.005; GBM22: 54.4%, P = 0.043). ABT-888 had no effect with radiotherapy alone but significantly enhanced survival in GBM12 when combined with concurrent radiotherapy/temozolomide. With multicycle therapy, ABT-888 further extended the survival benefit of temozolomide in the inherently sensitive GBM12 and GBM22 xenograft lines. However, after in vivo selection for temozolomide resistance, the derivative GBM12TMZ and GBM22TMZ lines were no longer sensitized by ABT-888 in combination with temozolomide, and a similar lack of efficacy was observed in two other temozolomide-resistant tumor lines. Thus, the sensitizing effects of ABT-888 were limited to tumor lines that have not been previously exposed to temozolomide, and these results suggest that patients with newly diagnosed glioblastoma may be more likely to respond to combined temozolomide/poly(ADP-ribose) polymerase inhibitor therapy than patients with recurrent disease. [Mol Cancer Ther 2009;8(2):OF407–8]