Outcome of kinematic alignment using patient-specific instrumentation versus mechanical alignment in TKA: a meta-analysis and subgroup analysis of randomised trials.

INTRODUCTION: Kinematic alignment (KA) in total knee arthroplasty (TKA) matches component position to the pre-arthritic anatomy of an individual patient, with the aim of improving functional outcomes. Recent randomised controlled trials (RCTs) comparing KA to traditional neutral mechanical alignment (MA) have been mixed. This collaborative study combined raw data from RCTs, aiming to compare functional outcomes between KA using patient-specific instrumentation (PSI) and MA, and whether any patient subgroups may benefit more from KA technique. MATERIALS AND METHODS: A literature search in PubMed, EMBASE and Cochrane databases identified four randomised controlled trials comparing patients undergoing TKA using PSI-KA and MA. Unpublished data including Western Ontario McMaster Universities Arthritis Index (WOMAC) and Knee Society Score (KSS) were obtained from study authors. Meta-analysis compared MA to KA change (post-op minus pre-op) scores. Subgroup-analysis on KA patients looked for subgroups more likely to benefit from KA and the impact of PSI accuracy. RESULTS: Meta-analyses of change scores in 229 KA patients versus 229 MA patients were no different from WOMAC (mean difference 3.4; 95% confidence interval - 0.5 to 7.3), KSS function (1.3, - 3.9 to 6.4) or KSS combined (7.2, - 0.8 to 15.2). A small advantage was seen for KSS pain in the KA group (3.6, 95% CI 0.2-7.1). Subgroup-analysis showed no difference between varus, valgus and neutral pre-operative alignment groups, and those who did and did not achieve KA plans. Pain-free patients at 1-year were more likely to achieve KA plans. CONCLUSION: Patient-reported outcome scores following TKA using PSI-KA are similar to MA. No identifiable subgroups benefited more from KA, and long-term results remain unknown. Inaccuracy of the PSI system used in KA patients could potentially affect outcome.

The impact of patient and surgical factors on the rate of infection after primary total knee arthroplasty: an analysis of 64,566 joints from the New Zealand Joint Registry.

AIMS: The aim of this study was to identify risk factors for prosthetic joint infection (PJI) following total knee arthroplasty (TKA). PATIENTS AND METHODS: The New Zealand Joint Registry database was analysed, using revision surgery for PJI at six and 12 months after surgery as primary outcome measures. Statistical associations between revision for infection, with common and definable surgical and patient factors were tested. RESULTS: A total of 64 566 primary TKAs have been recorded on the registry between 1999 and 2012 with minimum follow-up of 12 months. Multivariate analysis showed statistically significant associations with revision for PJI between male gender (odds ratio (OR) 1.85, 95% confidence interval (CI) 1.24 to 2.74), previous surgery (osteotomy (OR 2.45 95% CI 1.2 to 5.03), ligament reconstruction (OR 1.85, 95% CI 0.68 to 5.00)), the use of laminar flow (OR 1.6, 95% CI 1.04 to 2.47) and the use of antibiotic-laden cement (OR 1.93, 95% CI 1.19 to 3.13). There was a trend towards significance (p = 0.052) with the use of surgical helmet systems at six months (OR 1.53, 95% CI 1.00 to 2.34). CONCLUSION: These findings show that patient factors remain the most important in terms of predicting early PJI following TKA. Furthermore, we found no evidence that modern surgical helmet systems reduce the risk of PJI and laminar flow systems may actually increase risk in TKA. The use of this registry data assists the estimation of the risk of PJI for individual patients, which is important for both informed consent and the interpretation of infection rates at different institutions. TAKE HOME MESSAGE: Infection rates in TKA are related to both individual patient and surgical factors, and some modern methods of reducing infection may actually increase infection risk.

Unusual cause of deep vein thrombosis following dynamic hip screw fixation.

We report a case of profunda femoris false aneurysm following internal fixation of an intertrochanteric neck of femur fracture, caused by proximal migration of a fracture fragment. The case is unique in that the mode of presentation was that of deep venous thrombosis, due to extrinsic compression of the venous system by the false aneurysm. (Hip International 2004; 14: 262-4).

Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging.

The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.

Forecasting the nursing workforce in a dynamic health care market.

The ability to discern the interacting factors that affect supply and demand for nurses could help nurse educators and nurse leaders allocate resources to meet these needs. Forecasting models must take into account the interactions of three crucial groups of health care providers--physicians, nurse practitioners, and physician's assistants. Buerhaus has noted that market size, wages, preferences for nursing services, and availability of substitutes influence the demand for nursing services. Changes in nurse supply resulting from Medicare reimbursement for nursing services have not been studied, though it could safely be projected that such reimbursement will increase nurse supply. Nurses with baccalaureate degrees and advanced practice preparation will be in the greatest demand in ambulatory care, managed care, public health, and home care settings, raising concerns again that the educational mix is in need of adjustment upwards.

Photodynamic therapy of B16F10 murine melanoma with lutetium texaphyrin.

Photodynamic therapy (PDT) of pigmented melanoma has generally been unsuccessful because of insufficient light penetration in such tissues. In this study, the responsiveness of the heavily pigmented B16F10 murine melanoma to lutetium texaphyrin (PCI-0123), a water-soluble sensitizer with strong absorbance in the near infrared (700-760 nm), was examined. These studies were carried out in both normal and ApoE deficient C57BL/6 mice. The latter strain exhibits a lipoprotein profile more like humans (low density lipoprotein > high density lipoprotein) than rodents (high density lipoprotein >> low density lipoprotein). Under optimal conditions of drug dose, light dose, and interval between drug administration and irradiation--the median survival time of C57BL/6 tumor bearing mice was approximately doubled (29 d) compared with tumor bearing control animals (13 d). The life-span of the ApoE knockout mice was greater (33 d) than the C57BL/6 animals (23 d) when irradiation occurred 3 h after administration of a 10 micromol per kg drug dose. The greater efficacy of PDT in the ApoE deficient mice was associated with more rapid clearance of drug from the blood, greater accumulation of sensitizer in tumor tissue, and substantially greater drug binding to the very low density lipoprotein/low density lipoprotein plasma fraction. Confocal laser scanning microscopy showed that the predominant subcellular site of photosensitizer binding was to melanosomes; costaining was performed with Mel-5. Melanosomes are susceptible to oxidative stress. Photo-oxidation, mediated by PCI-0123 PDT, could potentially overload an already highly oxidized stressed state leading to cell death. The good tissue penetration depth achieved by PCI-0213 mediated PDT and the activation of melanosomes makes PDT of pigmented melanoma, for the first time, clinically relevant.

Creating statewide partnerships. The South Carolina experience.

Responding to demands that nursing leaders conduct business in creative proactive ways, the authors of this department share the work of the Robert Wood Johnson Foundation's national program, Colleagues in Caring: Regional Collaboratives for Nursing Work Force Development. The purpose of this initiative is to enhance regional and state collaborative planning and implement actions and policies to address the rapid changes occurring in the United States nursing labor market. This department, edited by Mary Fry Rapson, PhD, RN, CS, National Program Director, and Rebecca B. Rice, EdD, RN, National Deputy Director, presents the ongoing work of the program, highlighting the work of the 20 individual collaboratives. Regional approaches to the expected program outcomes and specific challenges and opportunities that are unique to each region's environment are included.

A case management curricular model. The challenge for nursing education.

Preparing students for practice in a managed care system requires restructuring of the nursing curriculum. The authors describe a case management curricular model as a framework for baccalaureate education. Processes used for curricular redesign and recommendations for knowledge and skills expected of baccalaureate program graduates are included. Examples of expected student case management performance behaviors and evaluation criteria are provided.

A multicenter clinical trial of Gadolite Oral Suspension as a contrast agent for MRI.

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49-1.18 for reader 1: .46-1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.

Localization and efficacy analysis of the phototherapeutic lutetium texaphyrin (PCI-0123) in the murine EMT6 sarcoma model.

Lutetium texaphyrin (PCI-0123) is a pure, water-soluble photodynamic therapy (PDT) agent that is activated by tissue-penetrating far red light. The sensitizer is highly fluorescent and exhibits a strong, broad emission signal at 750 nm. In vitro cellular uptake studies revealed an increase in sensitizer retention with incubation time. Confocal laser scanning microscopy demonstrated that the intracellular localization site of PCI-0123 is the lysosomes. Ensuing illumination of the EMT6 cells led to lysosomal breakup, extensive cytoplasmic blebbing and subsequent cell death. Noninvasive spectral imaging analysis of PCI-0123 fluorescence depicted selective drug uptake, compared to surrounding normal tissue, in EMT6 mammary sarcomas syngeneic to BALB/c mice. The PCI-0123 PDT was shown to effectively treat the EMT6 murine sarcoma. Irradiation (732 nm light) 3 h postintravenous injection of 10 mumol PCI-0123 per kg gave 100% cures (no evidence of cancer), whereas light exposure at 5 h resulted in 75% cures. Hematoxylin and eosin histologic examination of photoirradiated tumors indicated apoptosis of the EMT6 neoplasms at early times post-PDT progressing, with time, to extensive necrotic areas. Gel electrophoresis of extracted photoirradiated tumors showed the typical apoptotic DNA ladder pattern that increased in intensity following PDT treatment.

Phototherapy of cancer and atheromatous plaque with texaphyrins.

Cancer and cardiovascular disease are the leading causes of death in the western world. Photodynamic therapy (PDT) has demonstrated activity in the treatment of superficial cancerous lesions and as an intraoperative adjunct during surgical debulking. Texaphyrins are pure, synthetic water-soluble macrocycles that localize in both cancerous lesions and atheromatous plaque. Lutetium texaphyrin (PCI-0123) is activated by tissue-penetrating far red light (720-760 nm). Patient diagnosis and treatment planning is possible via magnetic resonance imaging (MRI) with the paramagnetic gadolinium texaphyrin (PCI-0120) or via fluorescence imaging using the diamagnetic PCI-0123. In this study it is shown that texaphyrins localize selectively in cancer and atheromatous plaque. PDT with PCI-0123 is found to cause selective photodamage to the diseased tissue. Specifically, PCI-0123 acts to eradicate the SMT-F murine mammary tumors and diet-induced atheromatous plaque in rabbits.

Lutetium texaphyrin (PCI-0123): a near-infrared, water-soluble photosensitizer.

Lutetium texaphyrin, PCI-0123, is a pure, water-soluble photosensitizer with a large broad absorption band centered at 732 nm. The compound was tested for photodynamic therapy (PDT) effectiveness in a murine mammary cancer model. The texaphyrin macrocycle as illustrated by magnetic resonance imaging and 14C-radiolabeled texaphyrin studies was shown to be tumor selective; a tumor-to-muscle ratio of 10.55 was seen after 5 h. Lutetium texaphyrin, at a drug dose of 20 mumol/kg with irradiation 5 h postinjection at 150 J/cm2 and 150 mW/cm2, had significant efficacy (P < 0.0001) in treating neoplasms of moderate size (40 +/- 14 mm3) and also had significant efficacy (P < 0.0001) in treating larger neoplasms (147 +/- 68 mm3). The PDT efficacy was correlated with the time interval between PCI-0123 administration and light exposure. A 100% cure rate was achieved when photoirradiation took place 3 h postinjection compared to 50% for 5 h using 10 mumol/kg and 150 J/cm2 at 150 mW/cm2. The PDT efficacy was attributable to the selective uptake/retention of the texaphyrin photosensitizer in addition to the depth of light penetration achievable at the 732 nm laser irradiation.

Gadolinium(III) texaphyrin: a tumor selective radiation sensitizer that is detectable by MRI.

Gadolinium(III) texaphyrin (Gd-tex2+) is representative of a new class of radiation sensitizers detectable by magnetic resonance imaging (MRI). This porphyrin-like complex has a high electron affinity [E1/2 (red.) approximately = -0.08 V versus normal hydrogen electrode] and forms a long-lived pi-radical cation upon exposure to hydrated electrons, reducing ketyl radicals, or superoxide ions. Consistent with these chemical findings, Gd-tex2+ was found to be an efficient radiation sensitizer in studies carried out with HT29 cells in in vitro as well as in in vivo single and multifraction irradiation studies with a murine mammary carcinoma model. Selective localization of Gd-tex2+ in tumors was confirmed by MRI scanning.

Experimental acute cerebral ischemia with reperfusion. Evaluation with gadolinium-texaphyrin.

RATIONALE AND OBJECTIVES: The authors explore the potential usefulness of the new contrast medium gadolinium (Gd)-texaphyrin (PCI-0101) in magnetic resonance imaging of experimental acute cerebral ischemia with reperfusion. METHODS: Four New Zealand white rabbits underwent 2 hours of transorbital occlusion of the left internal carotid, anterior, and middle cerebral arteries, followed by 2 hours of reperfusion with normal saline. Immediately thereafter, the rabbits were injected with 25 mumol/kg of 2 mmol/L Gd-texaphyrin and killed by barbiturate overdose. Postmortem T1- and T2-weighted coronal scans were performed at 1.5 Tesla and correlated with histopathologic findings. RESULTS: Postcontrast T1-weighted images showed high signal within extensive cortical and basal ganglia infarcts. Areas of high signal on T1-weighted images were less extensive than on T2-weighted images, and corresponded to only a portion of the region of neuronal damage seen histologically. Signal intensity of infarcted brain on postcontrast T1-weighted images was significantly greater than normal brain in the contralateral hemisphere (P < 0.0014). CONCLUSIONS: Experimental reperfused infarcts only 2 hours old demonstrate contrast enhancement with Gd-texaphyrin.

Imaging of human colon cancer xenograft with gadolinium-texaphyrin.

RATIONALE AND OBJECTIVES: The authors explore the efficacy of gadolinium (Gd)-texaphyrin (PCI-0101), an expanded porphyrin, as a contrast medium for magnetic resonance imaging of nude mice implanted with the human colon cancer xenograft LS174T. METHODS: Magnetic resonance images were obtained in six nude mice 7 to 8 days after implantation of LS174T cells in dorsal subcutaneous tissues. Spin-echo T1-weighted images were obtained at baseline and at 5, 15, and 60 minutes after injection of 10 or 20 mumols/kg of Gd-texaphyrin. Delayed images were obtained at 24 and 48 hours after injection. Region-of-interest measurements were taken of the tumors and of enhancing tumor rims at all time points. Percent enhancement was calculated and compared among the various time points. RESULTS: All tumors were enhanced after injection of Gd-texaphyrin. Heterogeneous patterns of enhancement were seen, with peak enhancement seen at the 15-minute time point; however, greater enhancement was seen at 48 hours than at 24 hours after Gd-texaphyrin intravenous injection. CONCLUSIONS: Gadolinium-texaphyrin may prove to be a useful contrast medium for magnetic resonance imaging of tumors.

Activation of mitogen-activated protein kinase by protein kinase C isotypes alpha, beta I and gamma, but not epsilon.

Treatment of CHO.T cells with either PMA or insulin led to the activation of MAP kinase by approximately 3-fold, and p90rsk by approximately 4-fold. Over-expression of the alpha, beta I or gamma isoforms of protein kinase C caused a substantial enhancement of the effect of PMA on the activation of MAP kinase and p90rsk, however, the effect of insulin was unchanged. Over-expression of the epsilon isoform of protein kinase C did not alter the effect of either PMA or insulin on the activation of MAP kinase and p90rsk. The results suggest that protein kinase C isotypes, alpha, beta I and gamma, but not epsilon, can mediate MAP kinase activation by PMA, and strongly support the hypothesis that protein kinase C isoforms can initiate distinct signalling pathways.

Developing workplace advocacy behaviors.

In this article, the authors describe the concept of workplace advocacy, workplace hazards experienced by hospital nurses, methods for teaching workplace advocacy behavior, and strategies for controlling specific workplace hazards. Workplace advocacy is a universally applicable concept for maintaining professional nursing practice. Staff development educators are key in helping staff nurses achieve autonomous nursing practice.

Gadolinium zeolite as an oral contrast agent for magnetic resonance imaging.

The purpose of this study was to evaluate efficacy and safety of a gadolinium (Gd) zeolite suspension as an oral MRI contrast agent. Serial dilutions of GADO-LITE Oral Suspension 1,2-300 micrograms of Gd(III)/mL) were prepared. MRI (T1 and T2 weighted) of standards and dogs (precontrast and postcontrast) were performed. Toxicity and Gd absorption were also assessed. Subsequently, 30 normal male adult volunteers were divided into six groups of five subjects each. Gd zeolite po suspension was administered before and after MRI in volumes and concentrations ranging from 250 to 1500 mL; 6 to 60 micrograms of Gd+3/mL. The images were rated (efficacy score) by a blinded reader. Vital signs, blood chemistries and urinalysis were recorded. Gadolite Oral Suspension produced excellent enhancement of the dog gastrointestinal (GI) tract. No toxicity or absorption of Gd was observed in dogs receiving doses up to 4 times the anticipated human dose daily for 14 consecutive days. In clinical trials, Gd zeolite significantly improved the efficacy scores for all groups and all pulsing sequences (all P values < .05). Efficacy scores and signal intensities generally increased with concentration and volume. No Gd was detected in blood or urine specimens. No significant adverse events were reported. Gd zeolite is a promising contrast medium for enhancement of the GI tract in MRI.

Influence of viscosity on WIN 39996 as a contrast agent for gastrointestinal magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The authors discuss the influence of viscosity on the imaging properties of WIN 39996 suspension. WIN 39996 suspension is a magnetically susceptible iron ferrite that provides negative (darkening) contrast enhancement in magnetic resonance imaging of the gastrointestinal tract. METHODS: The viscosity of WIN 39996 suspension was altered by various stress conditions (1 week to 4.5 months storage at temperatures of 5 degrees to 70 degrees C) or by various amounts of xanthan gum. Magnetic resonance imaging was performed in vitro on phantoms and in vivo on the gastrointestinal tract of anesthetized dogs. RESULTS: The results indicated that in vitro and in vivo imaging efficacies of WIN 39996 suspension depended on the viscosity, irrespective of the means by which the viscosity was altered. Specifically, the imaging quality was suitable at viscosities > or = 36.6 cp for in vitro imaging, and > 25 cp for in vivo imaging. The lower in vivo viscosity limit for magnetic resonance imaging compared with the in vitro limit may be due to gastrointestinal peristaltic activities continuously mixing the WIN 39996 suspension to prevent gravitational settling, and the enhancement of signal blackening by intraluminal WIN 39996 that was above and below the plane of image. CONCLUSIONS: It is speculated that the imaging quality of WIN 39996 suspension depends on the degree of dispersion of the magnetically susceptible iron ferrite in the WIN 39996 suspension, and that a minimum viscosity is needed to ensure such dispersion.