Total first metatarsophalangeal joint implant arthroplasty: a 30-year retrospective

The first metatarsophalangeal (MTP) joint is a frequent diseased-affected articulation encountered by the foot and ankle surgeon. Arthroplasty remains a favorable option for surgeons, because it preserves motion of the joint. The authors' focus at the Weil Foot and Ankle Institute has been on using double-stem silicone implants with titanium grommets, which may be a viable solution for affected articulations. The authors present their clinical results from over 30 years of experience with total first MTP joint implant arthroplasty at the Weil Foot and Ankle Institute.     

Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas

A phase I trial of ABT-888 (veliparib), a PARP inhibitor, in combination with topotecan, a topoisomerase I-targeted agent, was carried out to determine maximum tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of the combination in patients with refractory solid tumors and lymphomas. Varying schedules and doses of intravenous topotecan in combination with ABT-888 (10 mg) administered orally twice a day (BID) were evaluated. Plasma and urine pharmacokinetics were assessed and levels of poly(ADP-ribose) (PAR) and the DNA damage marker γH2AX were measured in tumor and peripheral blood mononuclear cells (PBMC). Twenty-four patients were enrolled. Significant myelosuppression limited the ability to coadminister ABT-888 with standard doses of topotecan, necessitating dose reductions. Preclinical studies using athymic mice carrying human tumor xenografts also informed schedule changes. The MTD was established as topotecan 0.6 mg/m2/d and ABT-888 10 mg BID on days one to five of 21-day cycles. Topotecan did not alter the pharmacokinetics of ABT-888. A more than 75% reduction in PAR levels was observed in 3 paired tumor biopsy samples; a greater than 50% reduction was observed in PBMCs from 19 of 23 patients with measurable levels. Increases in γH2AX response in circulating tumor cells (CTC) and PBMCs were observed in patients receiving ABT-888 with topotecan. We show a mechanistic interaction of a PARP inhibitor, ABT-888, with a topoisomerase I inhibitor, topotecan, in PBMCs, tumor, and CTCs. Results of this trial reveal that PARP inhibition can modulate the capacity to repair topoisomerase I-mediated DNA damage in the clinic.     

A critical appraisal of molecular xenomonitoring as a tool for assessing progress toward elimination of Lymphatic Filariasis

We used molecular xenomonitoring (MX, detection of filarial DNA in mosquitoes) to evaluate the impact of mass drug administration (MDA) in sentinel locations in Egypt with high (11.5%) and low (4.1%) baseline microfilaria prevalence rates. Blood-fed Culex pipiens were pooled by household and tested for Wuchereria bancrofti DNA by PCR. There was no significant relationship between the infection status of household residents and parasite DNA status of mosquitoes from the same houses. After 5 MDA rounds, parasite DNA rates in mosquitoes in high- and low-prevalence areas were reduced by 93.8% and 100% to 0.19% (95% CI: 0.076-0.382%) and 0% (95% CI: 0-0.045%), respectively. These changes were consistent with decreases in microfilaria prevalence rates in these sites; they provide insight regarding the minimal mosquito DNA rates necessary for sustained transmission of filariasis in Egypt. We conclude that MX is a powerful tool for monitoring the impact of MDA on filariasis endemicity and transmission.     

Symptomatic pituitary metastases from renal cell carcinoma

Symptomatic metastases to the pituitary (MP) from renal cell carcinoma (RCC) are rare. In this largest case series reported, we describe the clinical features, treatment and outcome of 5 patients. Over a 6-year period (2000–2006), we treated 5 patients (3 males; mean age 61 years) with large sellar masses and RCC. Four patients had a history of RCC, while in one, RCC was diagnosed after surgery. RCC was diagnosed a median of 11 years prior to diagnosis of MP (range 0–27 years). Four patients had previously developed distant metastases. Clinical presentation included bitemporal hemianopia (3 patients), lethargy (3), headaches (2) and diabetes insipidus (DI) (2). Panhypopituitarism was present in 3 patients and the other two had deficiency of at least ACTH and gonadotropin axes. Elevated prolactin was seen in 3 patients. MRI showed an enhancing sellar mass with suprasellar extension and chiasmal compression in all; prominent vascular flow voids were seen in 2. Three patients underwent transsphenoidal surgery and radiation, while 2 underwent radiotherapy alone. Four patients are alive (follow up 6–46 months); 1 patient died due to systemic metastases at 12 months. Metastases to the pituitary from RCC cause more severe hypopituitarism and visual dysfunction compared to those from other primaries, whereas DI is less common. MRI shows contrast enhancement, stalk involvement, sclerosis and/or erosion of sella and presence of vascular flow voids. Combined treatment using decompressive surgery and stereotactic radiotherapy may result in better outcomes.     

Neural correlates of perceptual filling-in of an artificial scotoma in humans

When a uniformly illuminated surface is placed eccentrically on a dynamic textured background, after a few seconds, it is perceived to disappear and be replaced by the background texture. Such texture filling-in is thought to occur in retinotopic visual cortex, but it has proven difficult to distinguish the contributions of invisible target and visible background to signals measured in these areas. Here, we used magnetoencephalography to measure time-dependent brain responses in human observers experiencing texture completion. We measured responses specifically associated with the filled-in target, by isolating neural population signals entrained at the frequency of flicker of the target. When perceptual completion occurred, and the target became invisible, there was significant reduction in the magnetoencephalography power at the target frequency over contralateral posterior sensors. However, even a subjectively invisible target nevertheless evoked frequency-specific signals compared with a no-target baseline. These data represent evidence for a persistent target-specific representation even for stimuli rendered invisible because of perceptual filling-in.     

Medial migration of intramedullary hip fixation devices: a biomechanical analysis

Introduction Intramedullary nails for fixation of extracapsular hip fractures have gained popularity recently. Although clinically successful, they are not devoid of complications. An infrequently reported complication is the medial migration of the femoral neck element (FNE) of the implant into the pelvis. The purpose of this study was to create a biomechanical model simulating this effect based on a clinical case radiographic analysis. Methods Eight clinical cases of medial migration were available for radiographic analysis. Medial migration was quantified and the fractures were classified. A biomechanical model was built comprising two fixtures containing the nail and FNE respectively. A pivot between the two fixtures, representing a deficient femoral calcar, simulated an unstable fracture type. Two pivot points were used for each nail. The constructs were tested using sinusoidal loading (40–800 N at 2 Hz) and medial migration was assessed. Five different nail designs (TFN, PFN, PFN-a, Gamma-3 and IMHS) were tested (overall 75 tests). Results All the five implants demonstrated medial migration to a similar distance. The TFN required the highest number of cycles (3127 ± 2569) and the IMHS the lowest (58.8 ± 3.6) although this difference did not reach statistical significance (P = 0.07). Changing the pivot point for the medial calcar did not alter the results significantly. All eight clinical cases demonstrated an unstable intertrochanteric fracture pattern (AO/OTA 32A2). Conclusions Discrete biomechanical conditions are required to reproduce medial migration of the FNE in cephalomedullary devices.