Arthroscopic partial meniscectomy vs non-surgical or sham treatment in patients with MRI-confirmed degenerative meniscus tears: a systematic review and meta-analysis with individual participant data from 605 randomised patients.

OBJECTIVE: To identify subgroups of patients with magnetic resonance imaging (MRI)-confirmed degenerative meniscus tears who may benefit from arthroscopic partial meniscectomy (APM) in comparison with non-surgical or sham treatment. METHODS: Individual participant data (IPD) from four RCTs were pooled (605 patients, mean age: 55 (SD: 7.5), 52.4% female) as to investigate the effectiveness of APM in patients with MRI-confirmed degenerative meniscus tears compared to non-surgical or sham treatment. Primary outcomes were knee pain, overall knee function, and health-related quality of life, at 24 months follow-up (0-100). The IPD were analysed in a one- and two-stage meta-analyses. Identification of potential subgroups was performed by testing interaction effects of predefined patient characteristics (e.g., age, gender, mechanical symptoms) and APM for each outcome. Additionally, generalized linear mixed-model trees were used for subgroup detection. RESULTS: The APM group showed a small improvement over the non-surgical or sham group on knee pain at 24 months follow-up (2.5 points (95% CI: 0.8-4.2) and 2.2 points (95% CI: 0.9-3.6), one- and two-stage analysis, respectively). Overall knee function and health-related quality of life did not differ between the two groups. Across all outcomes, no relevant subgroup of patients who benefitted from APM was detected. The generalized linear mixed-model trees did also not identify a subgroup. CONCLUSIONS: No relevant subgroup of patients was identified that benefitted from APM compared to non-surgical or sham treatment. Since we were not able to identify any subgroup that benefitted from APM, we recommend a restrained policy regarding meniscectomy in patients with degenerative meniscus tears.

Energy calibration of charged particle detectors using discrete and continuous energy spectra of 137Cs.

An improved method for energy calibration of particle detectors is presented utilizing both the discrete and continuous spectra from the conversion electrons and beta particles of a radioisotope of  137Cs. This method considers the instrument response against the discrete spectrum from the conversion electrons at 624.22 keV and the continuous spectrum from the beta particles emitted by the unique first forbidden transition in the energy range of approximately 120-513 keV. The instrument response is determined by fitting model functions to the measurements, from which the energy scale and energy resolution of the instrument are derived. Inclusion of the beta particles in this method enables a determination of the energy scale in a broader energy range as well as the DC-offset and non-linearity of the instrument. This is an improvement from the conventional method that only utilizes a mono-energetic peak from the conversion electrons. A detailed description of the procedure is provided, from constructing the model functions to determining the instrument response. Results of the method, as successfully applied to a space-borne instrument, are provided to demonstrate the method.

Effects of dexmedetomidine on inflammatory mediators after tourniquet-induced ischemia-reperfusion injury: a randomized, double-blinded, controlled study.

BACKGROUND: Tourniquet use during total knee arthroplasty (TKA) produces ischemia-reperfusion injury (IRI), with systemic release of inflammatory cytokines and reactive oxygen species upon tourniquet release. We conducted a randomized, placebo-controlled, double-blind trial to examine whether dexmedetomidine (DEX) as an adjunct during general anesthesia in patients undergoing unilateral TKA could attenuate the rise in inflammatory cytokines and oxidative stress. METHODS: Sixty-eight patients were randomized to either the control or DEX group. DEX was administered at a loading dose of 0.5 µg/kg, followed by an infusion of 0.4 µg/kg/h. We measured serum levels of malondialdehyde (biomarker of oxidative stress) and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) preinduction (baseline), 60 and 90 min post-tourniquet release. We also assessed hemodynamics, intraoperative remifentanil consumption, and postoperative pain scores and analgesic consumption. RESULTS: Malondialdehyde was higher than baseline after tourniquet release in both groups (P≤0.001), but the levels were similar between groups at all times. TNF-α was significantly higher than baseline at 60 min post-tourniquet release only in the control group (P=0.009). Serum IL-6 increased significantly above baseline at 60 and 90 min post-tourniquet release in both groups (P<0.001). At 90 min, IL-6 was significantly lower in the dexmedetomidine group than in the control group (P=0.049). Remifentanil consumption, heart rate, and pain scores were significantly lower in the dexmedetomidine group. CONCLUSIONS: Our results suggest that dexmedetomidine as an adjunct to general anesthesia attenuated the rise in proinflammatory cytokines, providing protective effects in tourniquet-induced IRI.

A randomized controlled clinical and radiological trial about outcomes of navigation-assisted TKA compared to conventional TKA: long-term follow-up.

PURPOSE: Well balanced knees with good alignment are essential for a well-functioning TKA with long survival of its implants. This prospective randomized study comparing navigation-assisted TKA and conventional TKA reported the clinical and radiological outcomes at a follow-up of 9 years. The purpose of this study was to compare the clinical and radiological outcomes for patients who underwent navigation-assisted TKA or conventional TKA after long-term follow-up. METHODS: A total of 80 patients (88 knees) were available for physical and radiological examination 9 years after TKA. Clinical outcomes were evaluated using HSS, WOMAC, and KS function and pain scores. And radiological outcomes of the component loosening and its survivorship during 9-year follow-up were also evaluated. RESULTS: There were no significant differences in the field of clinical outcomes between the two groups. In terms of radiological outcomes, the navigation group had fewer alignment outliers (7.3 vs 20 %, p = 0.006). Although the clinical outcomes showed no differences between the two groups, the survival rate was slightly better in the navigation group than in the conventional group without statistical significance (best-case scenario 100 vs 95.3 %, n.s., worst-case scenario 95.6 vs 88.4 %, n.s.). CONCLUSION: Navigation-assisted TKA produced better alignment outcomes and better survival rates than conventional instruments although some of the differences were not statistically significant. LEVEL OF EVIDENCE: I.

Reduced microvascular volume and hemispherically deficient vasoreactivity to hypercapnia in acute ischemia: MRI study using permanent middle cerebral artery occlusion rat model.

Vasoreactivity to hypercapnia has been used for assessing cerebrovascular tone and control altered by ischemic stroke. Despite the high prognostic potential, traits of hypercapnia-induced hemodynamic changes have not been fully characterized in relation with baseline vascular states and brain tissue damage. To monitor cerebrovascular responses, T2- and T2*-weighted magnetic resonance imaging (MRI) images were acquired alternatively using spin- and gradient-echo echo plannar imaging (GESE EPI) sequence with 5% CO2 gas inhalation in normal (n=5) and acute stroke rats (n=10). Dynamic relative changes in cerebrovascular volume (CBV), microvascular volume (MVV), and vascular size index (VSI) were assessed from regions of interest (ROIs) delineated by the percent decrease of apparent diffusion coefficient (ADC). The baseline CBV was not affected by middle cerebral artery occlusion (MCAO) whereas the baseline MVV in ischemic areas was significantly lower than that in the rest of the brain and correlated with ADC. Vasoreactivity to hypercapnic challenge was considerably attenuated in the entire ipsilesional hemisphere including normal ADC regions, in which unsolicited, spreading depression-associated increases of CBV and MVV were observed. The lesion-dependent inhomogeneity in baseline MVV indicates the effective perfusion reserve for accurately delineating the true ischemic damage while the cascade of neuronal depolarization is probably responsible for the hemispherically lateralized changes in overall neurovascular physiology.

A comparison of proximal and distal Chevron osteotomy, both with lateral soft-tissue release, for moderate to severe hallux valgus in patients undergoing simultaneous bilateral correction: a prospective randomised controlled trial.

Moderate to severe hallux valgus is conventionally treated by proximal metatarsal osteotomy. Several recent studies have shown that the indications for distal metatarsal osteotomy with a distal soft-tissue procedure could be extended to include moderate to severe hallux valgus. The purpose of this prospective randomised controlled trial was to compare the outcome of proximal and distal Chevron osteotomy in patients undergoing simultaneous bilateral correction of moderate to severe hallux valgus. The original study cohort consisted of 50 female patients (100 feet). Of these, four (8 feet) were excluded for lack of adequate follow-up, leaving 46 female patients (92 feet) in the study. The mean age of the patients was 53.8 years (30.1 to 62.1) and the mean duration of follow-up 40.2 months (24.1 to 80.5). After randomisation, patients underwent a proximal Chevron osteotomy on one foot and a distal Chevron osteotomy on the other. At follow-up, the American Orthopedic Foot and Ankle Society (AOFAS) hallux metatarsophalangeal interphalangeal (MTP-IP) score, patient satisfaction, post-operative complications, hallux valgus angle, first-second intermetatarsal angle, and tibial sesamoid position were similar in each group. Both procedures gave similar good clinical and radiological outcomes. This study suggests that distal Chevron osteotomy with a distal soft-tissue procedure is as effective and reliable a means of correcting moderate to severe hallux valgus as proximal Chevron osteotomy with a distal soft-tissue procedure.

The role of waixenicin A as transient receptor potential melastatin 7 blocker.

Transient receptor potential melastatin 7 (TRPM7) plays a role in a number of physiological and pharmacological functions in variety of cells. The aim of this study was to clarify the role for TRPM7 channels and the effect of waixenicin A on the pacemaking activity of interstitial cells of Cajal (ICCs) and on the cell viability of the human gastric and breast adenocarcinoma cell lines, AGS and MCF-7, respectively. Waixenicin A decreased the amplitude of pacemaker potentials in cultured ICC clusters and inhibited TRPM7 currents, but had no effect on Ca(2+) -activated Cl(-) conductance (ANO1). Furthermore, waixenicin A was found to inhibit the growth and survival of AGS and MCF-7 cells. These findings indicate that TRPM7 channel modulates intestinal motility and regulates the pathophysiology of human gastric and breast adenocarcinoma cells. These findings suggest that TRPM7 channel be considered a potential target for the treatment of gut motor disorders and gastric and breast cancer.

Aspects of bioanalytical method validation for the quantitative determination of trace elements.

Bioanalytical methods are used to quantitatively determine the concentration of drugs, biotransformation products or other specified substances in biological matrices and are often used to provide critical data to pharmacokinetic or bioequivalence studies in support of regulatory submissions. In order to ensure that bioanalytical methods are capable of generating reliable, reproducible data that meet or exceed current regulatory guidance, they are subjected to a rigorous method validation process. At present, regulatory guidance does not necessarily account for nuances specific to trace element determinations. This paper is intended to provide the reader with guidance related to trace element bioanalytical method validation from the authors' perspective for two prevalent and powerful instrumental techniques: inductively coupled plasma-optical emission spectrometry and inductively coupled plasma-MS.

Sensitivity of MRI tumor biomarkers to VEGFR inhibitor therapy in an orthotopic mouse glioma model.

MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI) and a slight decrease in the water apparent diffusion coefficient (ADC) were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV), relative microvascular blood volume (rMBV), transverse relaxation time (T2), blood vessel permeability (K(trans)), and extravascular-extracellular space (ν(e)). The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology.

Delayed-type hypersensitivity reaction to piperacillin/tazobactam in a patient with an infected total knee replacement.

We describe a patient who developed a delayed-type hypersensitivity reaction to piperacillin/tazobactam in the cement beads and a spacer inserted at revision of total replacement of the left knee. We believe that this is the first report of such a problem. Our experience suggests that a delayed-type hypersensitivity reaction should be considered when a mixture of antibiotics such as piperacillin/tazobactam has been used in the bone cement, beads or spacer and the patient develops delayed symptoms of pain or painful paraesthesiae, fever, rash and abnormal laboratory findings in the absence of infection. The diagnosis was made when identical symptoms were induced by a provocation challenge test.

The complications of high tibial osteotomy: closing- versus opening-wedge methods.

We compared the incidence and severity of complications during and after closing- and opening-wedge high tibial osteotomy used for the treatment of varus arthritis of the knee, and identified the risk factors associated with the development of complications. In total, 104 patients underwent laterally based closing-wedge and 90 medial opening-wedge high tibial osteotomy between January 1993 and December 2006. The characteristics of each group were similar. All the patients were followed up for more than 12 months. We assessed the outcome using the Hospital for Special Surgery knee score, and recorded the complications. Age, gender, obesity (body mass index > 27.5 kg/m(2)), the type of osteotomy (closing versus opening) and the pre-operative mechanical axis were subjected to risk-factor analysis. The mean Hospital for Special Surgery score in the closing and opening groups improved from 73.4 (54 to 86) to 91.8 (81 to 100) and from 73.8 (56 to 88) to 93 (84 to 100), respectively. The incidence of complications overall and of major complications in both groups was not significantly different (p = 0.20 overall complication, p = 0.29 major complication). Logistic regression analysis adjusting for obesity and the pre-operative mechanical axis showed that obesity remained a significant independent risk factor (odds ratio = 3.23) of a major complication after high tibial osteotomy. Our results suggest that the opening-wedge high tibial osteotomy can be an alternative treatment option for young patients with medial compartment osteoarthritis and varus deformity.

The effect of anteroposterior laxity on the range of movement and knee function following a cruciate-retaining total knee replacement.

The amount of anteroposterior laxity required for a good range of movement and knee function in a cruciate-retaining total knee replacement (TKR) continues to be debated. We undertook a retrospective study to evaluate the effects of anteroposterior laxity on the range of movement and knee function in 55 patients following the e-motion cruciate-retaining TKR with a minimum follow-up of two years. The knees were divided into stable (anteroposterior translation, < or = 10 mm, 38 patients) and unstable (anteroposterior translation, > 10 mm, 17) groups based on the anteroposterior laxity, measured using stress radiographs. We compared the Hospital for Special Surgery (HSS) scores, the Western Ontario MacMasters University Osteoarthritis (WOMAC) index, weight-bearing flexion, non-weight-bearing flexion and the reduction of flexion under weight-bearing versus non-weight-bearing conditions, which we referred to as delta flexion, between the two groups at the final follow-up. There were no differences between the stable and unstable groups with regard to the mean HHS and WOMAC total scores, as well as weight-bearing and non-weight-bearing flexion (p = 0.277, p = 0.082, p = 0.095 and p = 0.646, respectively). However, the stable group had a better WOMAC function score and less delta flexion than the unstable group (p = 0.011 and p = 0.005, respectively). Our results suggest that stable knees with laxity < or = 10 mm have a good functional outcome and less reduction of flexion under weight-bearing conditions than unstable knees with laxity > 10 mm following an e-motion cruciate-retaining TKR.

In vivo validation of MRI vessel caliber index measurement methods with intravital optical microscopy in a U87 mouse brain tumor model.

The vessel caliber index (VCI), a magnetic resonance imaging biomarker of the average blood vessel diameter, is increasingly being used as a tool for assessing tumor angiogenesis and response to antiangiogenic therapy. However, although the VCI has been correlated with histological vessel diameters, good quantitative agreement with histology has been lacking. In addition, no VCI validation studies have been performed in vivo where the structural deformations frequently associated with histological tissue preparation are not present. This study employs intravital optical microscopy (IVM) measurements of cerebral blood vessel diameters in a mouse orthotopic glioma model to provide the first such in vivo validation. Two VCI correlation models, both a linear and a 3/2-power dependence on the DeltaR2*/DeltaR2 ratio, were compared with the IVM data. The linear VCI model, determined from steady-state susceptibility contrast (SSC) images, was found to be in excellent quantitative agreement with the intravitally determined VCI for separate tumor size matched groups of mice. In addition, preliminary data indicate that the VCI is independent of whether a dynamic susceptibility contrast or SSC measurement method is used.

Cementless total ankle arthroplasty in diabetic neuropathic arthropathy.

BACKGROUND: Neuropathic arthropathy (Charcot joint) is a progressive degenerative disease of a joint that may lead to severe deformity and dysfunction and it is now recognized that diabetes is the leading cause of Charcot joint. When the ankle is involved and conservative treatment fails arthrodesis has commonly been performed, whereas arthroplasty has previously been considered to be contraindicated. A total ankle arthroplasty in Charcot ankle has not been previously reported. CASE REPORT: We report the case of a 45-year old, diabetic woman with unilateral Charcot ankle. CONCLUSIONS: The woman successfully completed a rehabilitation programme and, 2 years after total ankle arthroplasty, achieved independence.

Arthroscopic release for painful subtalar stiffness after intra-articular fractures of the calcaneum.

We describe the surgical technique and results of arthroscopic subtalar release in 17 patients (17 feet) with painful subtalar stiffness following an intra-articular calcaneal fracture of Sanders' type II or III. The mean duration from injury to arthroscopic release was 11.3 months (6.4 to 36) and the mean follow-up after release was 16.8 months (12 to 25). The patient was positioned laterally and three arthroscopic portals were placed anterolaterally, centrally and posterolaterally. The sinus tarsi and lateral gutter were debrided of fibrous tissue and the posterior talocalcaneal facet was released. In all, six patients were very satisfied, eight were satisfied and three were dissatisfied with their results. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score improved from a mean of 49.4 points (35 to 66) pre-operatively to a mean of 79.6 points (51 to 95). All patients reported improvement in movement of the subtalar joint. No complications occurred following operation, but two patients subsequently required subtalar arthrodesis for continuing pain. In the majority of patients a functional improvement in hindfoot function was obtained following arthroscopic release of the subtalar joint for stiffness and pain secondary to Sanders type II and III fractures of the calcaneum.

Septic arthritis of hip after radiotherapy for carcinoma of cervix.

Radiation-induced damage to the bone is characterised by four main pathological findings: osteoporosis, bone-marrow fibrosis, trabecular microfractures and disseminated areas of focal necrosis. The complications of radiotherapy affecting hip and pelvis are well known, but septic arthritis of the hip joint following pelvic irradiation is a rare occurrence. Radiation-induced damage associated with a compromised host defence may be considered responsible for this complication. We report septic arthritis of hip joint in a 64-year-old woman who was treated with pelvic radiotherapy for carcinoma of the cervix eight years ago. She was successfully treated by two-stage reconstruction, consisting of debridement and antibiotic-loaded cement spacer insertion in the first stage and total hip replacement in the second stage.

Comparison of functional results with navigation-assisted minimally invasive and conventional techniques in bilateral total knee arthroplasty.

This study was undertaken to compare the clinical and radiological results achieved using navigation-assisted minimally invasive surgery (NA-MIS) and conventional (CON) techniques in 42 bilateral total knee arthroplasty (TKA) patients with a minimum follow-up of one year. Clinical evaluations were performed using range of motion (ROM), Hospital for Special Surgery (HSS) scores, and Western Ontario and McMaster University (WOMAC) scores (pain, functional, and total) at 3, 6 and 9 months and one year postoperatively. Patients' subjective preferences and radiological indices, including mechanical axis and coronal inclinations of the prostheses, were compared at one year postoperatively. NA-MIS TKA yielded better HSS and WOMAC total scores than CON TKA up to six months, and a better WOMAC pain score up to 9 months. However, these differences were not significant at one year postoperatively. ROM was comparable in both groups at all times, but more patients preferred the NA-MIS side to the CON side. Radiological results showed no differences in mean values between the two surgical groups, although the NA-MIS group contained fewer outliers than the CON group. In conclusion, NA-MIS TKA was associated with better clinical results up to 6 or 9 months after surgery, giving more accurate leg alignment than CON TKA.

Degradation of plant wastes by anaerobic process using rumen bacteria.

An operational reactor has been designed for the fermentation of a pure culture of Fibrobacter succinogenes with the constraints of strict anaerobic condition. The process is controlled by measurements of pH, redox, temperature and CO2 pressure; it allows an efficient degradation (67%) of lignocellulosic wastes such as a mixture of wheat straw, soya bean cake and green cabbage.

Large-scale growth and taxane production in cell cultures of Taxus cuspidata (Japanese yew) using a novel bioreactor.

A novel type of bioreactor was successfully developed for the production of taxol and its precursors by culturing cells of Taxus cuspidata (Japanese yew) on a pilot-scale. Rapidly growing cell lines were selected from callus cultures derived from immature embryos of yew. The cells were inoculated in 20-l capacity bioreactors of different types to test the growth performance. The models of small-scale bioreactors incorporated in this study included a balloon-type bubble bioreactor (BTBB), a bubble-column bioreactor (BCB), a BCB with a split-plate internal loop, a BCB with a concentric draught-tube internal loop, a BCB with a fluidized bed bioreactor, and two different models of stirred tank reactors. Among the reactors, BTBB appeared to be the most efficient in promoting cell growth. The doubling time of cell growth in BTBB was 12 days with a 30% inoculation cell density. The optimum time for medium replacement or feeding was 12-15 days after inoculation as determined by monitoring both the levels of sugars and medium conductivity. When yew tree cells were grown in different sizes (100-500-l) of BTBBs, more than 70% cell viability was recorded at the time of harvest. The growth pattern of the cells in the pilot-scale BTBB appeared to be the same as that of cells in the 20-l bioreactors. Approximately 3 mg/l of taxol and 74 mg/l total taxanes were obtained after 27 days of culture.