Multi-Body 3D-2D Registration for Robot-Assisted Joint Reduction: Preclinical Evaluation in the Ankle Syndesmosis.

Purpose: Existing methods to improve the accuracy of tibiofibular joint reduction present workflow challenges, high radiation exposure, and a lack of accuracy and precision, leading to poor surgical outcomes. To address these limitations, we propose a method to perform robot-assisted joint reduction using intraoperative imaging to align the dislocated fibula to a target pose relative to the tibia. Methods: The approach (1) localizes the robot via 3D-2D registration of a custom plate adapter attached to its end effector, (2) localizes the tibia and fibula using multi-body 3D-2D registration, and (3) drives the robot to reduce the dislocated fibula according to the target plan. The custom robot adapter was designed to interface directly with the fibular plate while presenting radiographic features to aid registration. Registration accuracy was evaluated on a cadaveric ankle specimen, and the feasibility of robotic guidance was assessed by manipulating a dislocated fibula in a cadaver ankle. Results: Using standard AP and mortise radiographic views registration errors were measured to be less than 1 mm and 1° for the robot adapter and the ankle bones. Experiments in a cadaveric specimen revealed up to 4 mm deviations from the intended path, which was reduced to <2 mm using corrective actions guided by intraoperative imaging and 3D-2D registration. Conclusions: Preclinical studies suggest that significant robot flex and tibial motion occur during fibula manipulation, motivating the use of the proposed method to dynamically correct the robot trajectory. Accurate robot registration was achieved via the use of fiducials embedded within the custom design. Future work will evaluate the approach on a custom radiolucent robot design currently under construction and verify the solution on additional cadaveric specimens.

Immunological Methods to Study Monoclonal Antibody Activity in Chronic Lymphocytic Leukaemia.

Over recent decades it has become increasingly apparent that malignant cells, including chronic lymphocytic leukemia (CLL) cells, do not exist in isolation. Rather they coalesce with numerous "normal" cells of the body and, in the case of CLL, inhabit key immunological niches within secondary lymphoid organs (SLO), where a plethora of stromal and immune cells mediate their growth and survival. With the advent and approval of targeted immune therapies such as monoclonal antibodies (mAb), which elicit their efficacy by engaging immune-mediated effector mechanisms, it is important to develop accurate methods to measure their activities. Here, we describe a series of reliable assays capable of measuring important antibody-mediated effector functions: antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) that measure these immune activities.

Shoulder-Mounted Robot for MRI-guided arthrography: Accuracy and mounting study.

A new version of our compact and lightweight patient-mounted MRI-compatible 4 degree-of-freedom (DOF) robot for MRI-guided arthrography procedures is introduced. This robot could convert the traditional two-stage arthrography procedure (fluoroscopy-guided needle insertion followed by a diagnostic MRI scan) to a one-stage procedure, all in the MRI suite. The results of a recent accuracy study are reported. A new mounting technique is proposed and the mounting stability is investigated using optical and electromagnetic tracking on an anthropomorphic phantom. Five volunteer subjects including 2 radiologists were asked to conduct needle insertion in 4 different random positions and orientations within the robot's workspace and the displacement of the base of the robot was investigated during robot motion and needle insertion. Experimental results show that the proposed mounting method is stable and promising for clinical application.

A Prototype Body-Mounted MRI-Compatible Robot for Needle Guidance in Shoulder Arthrography.

A novel compact and lightweight patient-mounted MRI-compatible robot has been designed for MRI image-guided interventions. This robot is intended to enable MRI-guided needle placement as done in shoulder arthrography. The robot could make needle placement more accurate and simplify the current workflow by converting the traditional two-stage arthrography procedure (fluoroscopy-guided needle insertion followed by a diagnostic MRI scan) to a one-stage procedure (streamlined workflow all in MRI suite). The robot has 4 degrees of freedom (DOF), two for orientation of the needle and two for needle positioning. The mechanical design was based on several criteria including rigidity, MRI compatibility, compact design, sterilizability, and adjustability. The proposed workflow is discussed and initial MRI compatibility experiments are presented. The results show that artifacts in the region of interest are minimal and that MRI images of the shoulder were not adversely affected by placing the robot on a human volunteer.

Is knowledge and practice safer in England after the release of national guidance on the resuscitation of patients in mental health and learning disabilities?

ACCESSIBLE SUMMARY: This paper reports on the issue of resuscitation in mental health inpatient environments. It reviews the literature on national standards and best practice when emergency situations arise in mental health settings. The discussion on the best practice literature takes place alongside the reporting of a national evaluation of how National Patient Safety Agency improvement guidelines for the provision for life support, and resuscitation for mental health service users was effectively implemented across health-care providers in England. Methods used to establish the effective use of the guidelines include feedback from clinical staff and staff responsible for the implementation of the new national standards for resuscitation. Serious incident data were also compared prior to the release of the national guidelines and after the guideline release dates. This included looking at events around choking and cardiac/respiratory arrest in inpatient areas. There were five deaths post-implementation of the guidelines that were considered to have serious enough error associated with the resuscitation process. This was down from 18 prior to the release of the guidelines. However, our survey showed that despite organisations reporting 100% compliance with the implementation of the guidelines, around half of frontline clinical staff were not aware of them. Although our survey responses show a contradiction between organisational and clinical staff awareness, our analysis suggests a reduction in moderate and severe harm cases and of deaths. There is evidence of a reduction in the worst types of error resulting in death, albeit with small numbers. In 2008, the National Patient Safety Agency issued a Rapid Response Report (RRR) aimed at health-care organisations providing inpatient care for mental health and learning disability patients, requiring organisations to make proper provision for life support and resuscitation for these patients. This paper examines whether effective implementation of the RRR recommendations had occurred across health providers in England. The methods used in this paper are the following: (1) Questionnaires were distributed nationally to clinical staff and implementation leads; (2) A national comparison of the number and severity of pre- and post-RRR release-related incidents involving choking/cardiac/respiratory arrest in Mental Health and Learning Disabilities settings was conducted; (3) Organisational compliance with the patient safety alert for all National Health Service Organisations in England was measured. There were five deaths post-implementation of the RRR that were considered to have serious enough error associated with the resuscitation. This was down from 18 deaths pre the RRR release. Although our survey responses show a contradiction between organisational implementation and clinical staff awareness, our analysis suggests a reduction in moderate and severe harm cases and of deaths. There is evidence of a reduction in the worst types of error resulting in death, albeit with small numbers.

Note: cryogenic microstripline-on-Kapton microwave interconnects.

Simple broadband microwave interconnects are needed for increasing the size of focal plane heterodyne radiometer arrays. We have measured loss and crosstalk for arrays of microstrip transmission lines in flex circuit technology at 297 and 77 K, finding good performance to at least 20 GHz. The dielectric constant of Kapton substrates changes very little from 297 to 77 K, and the electrical loss drops. The small cross-sectional area of metal in a printed circuit structure yields overall thermal conductivities similar to stainless steel coaxial cable. Operationally, the main performance tradeoffs are between crosstalk and thermal conductivity. We tested a patterned ground plane to reduce heat flux.

Augmented environments for minimally invasive therapy: implementation barriers from technology to practice.

Augmented environments for medical applications have been explored and developed in an effort to enhance the clinician's view of anatomy and facilitate the performance of minimally invasive procedures. These environments must faithfully represent the real surgical field and require seamless integration of pre- and intra-operative imaging, surgical instrument tracking and display technology into a common framework centered around the patient. However, few image guidance environments have been successfully translated into clinical use. Several challenges that contribute to the slow progress of integrating such environments into clinical practice are discussed here in terms of both technical and clinical limitations.

Round-bale feeder design affects hay waste and economics during horse feeding.

Many horse owners find round bales convenient, less labor intensive, and more affordable than other hay types, but report an inability to control horse BW gain and excessive hay waste. The objectives were to compare hay waste, hay intake, and payback of 9 round-bale feeders and a no-feeder control when used during horse feeding. Nine round-bale feeders were tested: Cinch Net, Cone, Covered Cradle, Hayhut, Hay Sleigh, Ring, Tombstone, Tombstone Saver, and Waste Less. Each feeder design was placed on the ground in a dirt paddock. Five groups of 5 horses were fed in rotation for a 4-d period with each feeder. Every fourth day, groups were rotated among paddocks and a new round bale was placed in each feeder. In the 5 paddocks used, 5 feeders were installed for d 1 through 20, and the remaining 4 feeders and no-feeder control were installed for d 21 through 40. Groups of horses were sequentially assigned to feeders using two 5 × 5 Latin squares, the first for d 1 through 20, the second for d 21 through 40. Horse groups of similar age, BW, breed, and sex were formed from 25 Quarter Horse and Thoroughbred geldings and open mares (means: 11 yr; 541 kg of BW). Hay on the ground surrounding the feeder was collected daily, dried, and weighed. The total amount of hay removed around each feeder for a 4-d period was considered waste. Dry matter intake was estimated as the difference between hay disappearance and waste. Number of months for the reduction in waste to repay feeder cost (payback) were calculated using hay valued at $110/t, and improved feeder efficiency over the control. Feeder design did not affect hay intake (P > 0.05); all feeders resulted in an estimated hay intake of 2.0 to 2.4% BW; the no-feeder control resulted in a reduced intake of 1.3% BW (P = 0.001). Mean percentage of hay waste differed among feeders (P < 0.001): Waste Less, 5%; Cinch Net, 6%; Hayhut, 9%; Covered Cradle, 11%; Tombstone Saver, 13%; Tombstone, Cone, and Ring, 19%; Hay Sleigh, 33%; and no-feeder control, 57%. Feeder design also affected payback (P < 0.01). The Cinch Net paid for itself in less than 1 mo; Tombstone and Ring, 2 mo; Hayhut and Tombstone Saver, 4 mo; Hay Sleigh, 5 mo; Waste Less, 8 mo; Cone, 9 mo; and Covered Cradle, 20 mo. Round-bale feeder design affected hay waste and payback, but not estimated hay intake or BW change during horse feeding.

Involving the patient to ask about hospital hand hygiene: a National Patient Safety Agency feasibility study.

Healthcare-associated infections (HAIs) affect at least 300,000 patients annually in the UK and represent a significant, yet largely preventable, burden to healthcare systems. Hand hygiene by healthcare workers (HCWs) is the leading prevention measure, but compliance with good practice is generally low. The UK National Patient Safety Agency surveyed the public, inpatients, and HCWs, particularly frontline clinical staff and infection control nurses, in five acute care hospitals to determine whether they agreed that a greater level of involvement and engagement with patients would contribute to increased compliance with hand hygiene and reduce HAIs. Fifty-seven percent (302/530) of the public were unlikely to question doctors on the cleanliness of their hands as they assumed that they had already cleaned them. Forty-three percent (90/210) of inpatients considered that HCWs should know to clean their hands and trusted them to do so, and 20% (42/210) would not want HCWs to think that they were questioning their professional ability to do their job correctly. Most HCWs surveyed (178/254, 71%) said that HAI could be reduced to a greater or lesser degree if patients asked HCWs if they had cleaned their hands before touching them. Inviting patients to remind HCWs about hand hygiene through the provision of individual alcohol-based hand-rub containers and actively supporting an 'It's OK to ask' attitude were perceived as the most useful interventions by both patients and HCWs. However, further work is required to refute the myth among HCWs that patient involvement undermines the doctor- or HCW-patient relationship.

Quantitative measurement of CyberKnife robotic arm steering.

Respiratory motion is a significant and challenging problem for radiation medicine. Without adequate compensation for respiratory motion, it is impossible to deliver highly conformal doses to tumors in the thorax and abdomen. The CyberKnife frameless stereotactic radiosurgery system with Synchrony provides respiratory motion adaptation by monitoring skin motion and dynamically steering the beam to follow the moving tumor. This study quantitatively evaluated this beam steering technology using optical tracking of both the linear accelerator and a ball-cube target. Respiratory motion of the target was simulated using a robotic motion platform and movement patterns recorded from previous CyberKnife patients. Our results show that Synchrony respiratory tracking can achieve sub-millimeter precision when following a moving object.

Detection of 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP)-DNA adducts in human pancreatic tissues.

Recent epidemiological investigations have observed an association between the consumption of grilled or barbecued meat and an increased risk of pancreatic cancer, suggesting that dietary exposure to heterocyclic aromatic amines (HCA) may contribute to the development of this disease. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP) is the most abundant HCA found in well-done and grilled meats. To determine whether HCA-induced DNA damage is present in the human pancreas, immunohistochemistry and computer-assisted image analysis were used to measure PhIP-DNA adducts in 54 normal pancreatic tissues (N) from persons without pancreatic cancer and in 38 normal adjacent pancreatic tissues (A) and in 39 cancer tissues (T) from 68 patients with pancreatic adenocarcinoma. PhIP-DNA adducts were detected in 53 N, 34 A and 39 T samples. Mean values (+/-SD) of the absorbency for PhIP staining were 0.22+/-0.04, 0.24+/-0.04, and 0.24+/-0.03 for N, A, and T samples, respectively (p=0.004). Using the median absorbency (0.21) of the samples from normal controls as the cut-off, 71% of A and 77% of T tissues, compared with 48% of N tissues, were distributed in the higher range (p=0.009). The odds ratio of pancreatic cancer was 3.4 (95% confidence interval 1.5-7.5, p=0.002) for individuals with a higher level of PhIP-DNA adducts. This is the first report of the detection of PhIP-DNA adducts in human pancreatic tissue samples obtained from patients with unknown exposure to HCA. Although limited by the small sample size, these preliminary results suggest that PhIP exposure may contribute to human pancreatic cancer development.

A novel end-effector design for robotics in image-guided needle procedures.

BACKGROUND: Robotic end-effectors are being developed to facilitate image-guided minimally invasive needle-based procedures, such as tumour ablation, biopsy, thoracentesis and blood sampling. METHODS: A novel mechanical end-effector was designed to address the challenges associated with any major needle-based procedure, focusing on liver biopsy and ablation. In this end-effector embodiment, the distal end of a single articulating arm can grip needles and instruments and allows a fairly high number of degrees of freedom of movement during the complex motions associated with positioning and driving needles, as well as the periodic motions associated with breathing patterns. Tightening a cable that runs through the articulations fixes the arm in a rigid state, allowing insertion of the gripped needle. RESULTS: A design is presented that will require electro-mechanical stimulation and remote joystick control. The associated forces of cranial-caudal motion of soft tissue organs affects design constraints. A simulation study defined the process with tissue phantoms with mechanical properties in the range of hepatic tissue and the overlying abdominal wall. The robotic arm coupled with our end-effector could be deployed in an image-guided interventional suite. CONCLUSIONS: Such a switch-able and flexible mode for a robotic arm could overcome much of the current limitations for automated needle placements for mobile targets, and could mitigate risks from breathing or patient motion with a rigid needle gripper in place.

Precision placement of instruments for minimally invasive procedures using a "needle driver" robot.

Medical practice continues to move toward less invasive procedures. Many of these procedures require the precision placement of a needle in the anatomy. Over the past several years, our research team has been investigating the use of a robotic needle driver to assist the physician in this task. This paper summarizes our work in this area. The robotic system is briefly described, followed by a description of a clinical trial in spinal nerve blockade. The robot was used under joystick control to place a 22 gauge needle in the spines of 10 patients using fluoroscopic imaging. The results were equivalent to the current manual procedure. We next describe our follow-up clinical application in lung biopsy for lung cancer screening under CT fluoroscopy. The system concept is discussed and the results of a phantom study are presented. A start-up company named ImageGuide has recently been formed to commercialize the robot. Their revised robot design is presented, along with plans to install a ceiling-mounted version of the robot in the CT fluoroscopy suite at Georgetown University.

Feasibility of four-dimensional conformal planning for robotic radiosurgery.

Organ motion can have a severe impact on the dose delivered by radiation therapy, and different procedures have been developed to address its effects. Conventional techniques include breath hold methods and gating. A different approach is the compensation for target motion by moving the treatment beams synchronously. Practical results have been reported for robot based radiosurgery, where a linear accelerator mounted on a robotic arm delivers the dose. However, not all organs move in the same way, which results in a relative motion of the beams with respect to the body and the tissues in the proximity of the tumor. This relative motion can severely effect the dose delivered to critical structures. We propose a method to incorporate motion in the treatment planning for robotic radiosurgery to avoid potential overdosing of organs surrounding the target. The method takes into account the motion of all considered volumes, which is discretized for dose calculations. Similarly, the beam motion is taken into account and the aggregated dose coefficient over all discrete steps is used for planning. We simulated the treatment of a moving target with three different planning methods. First, we computed beam weights based on a 3D planning situation and simulated treatment with organ motion and the beams moving synchronously to the target. Second, beam weights were computed by the 4D planning method incorporating the organ and beam motion and treatment was simulated for beams moving synchronously to the target. Third, the beam weights were determined by the 4D planning method with the beams fixed during planning and simulation. For comparison we also give results for the 3D treatment plan if there was no organ motion and when the plan is delivered by fixed beams in the presence of organ motion. The results indicate that the new 4D method is preferable and can further improve the overall conformality of motion compensated robotic radiosurgery.

Significance of post-chemoradiation biopsy in predicting residual esophageal carcinoma in the surgical specimen.

Pathologic complete response in the resected esophagus can be achieved in approximately 30% of patients with locally advanced esophageal or gastroesophageal junction carcinoma after preoperative chemoradiation therapy. These patients tend to have a longer survival than those who have less than pathologic complete response. Post-chemoradiation esophageal biopsy (PCEB) is used to check for the presence of residual tumor before a definitive resection is performed, but the clinical significance of PCEB findings is not clear due to the possibility of sampling bias and the superficial nature of the specimen obtained. We evaluated the use of PCEB (defined as biopsy taken within 30 days before esophagectomy) in predicting residual cancer in post-treatment esophagectomy specimens. PCEB was performed in 65 of 183 (36%) patients with locally advanced esophageal or gastroesophageal junction carcinoma, who received preoperative chemoradiation therapy. The cancer status in PCEB was correlated with the residual cancer in the esophagectomy specimens. PCEB had no cancer in 80% (52 of 65) of patients (Bx-negative) and cancer in 20% (13 of 65) of patients (Bx-positive). There was no difference in the presence of residual cancer (either in esophagus or lymph node) in esophagectomy specimens between Bx-negative patients (77%, 40 of 52) or Bx-positive patients (92%, 12 of 13), P = 0.44. The positive predictive value of biopsy was 92% (12 of 13), negative predictive value 23% (12 of 52), sensitivity 23% (12 of 52) and specificity 92% (12 of 13). There was no difference in the residual cancer staging in the esophagectomy specimen between Bx-positive and Bx-negative patients. In contrast, residual metastatic carcinoma in lymph nodes was more frequent in Bx-positive patients (69.2%, 9 of 13) than in Bx-negative patients (28.8%, 15 of 52), P = 0.01. Our data suggest that PCEB is a specific but not a sensitive predictor of residual cancer following esophagectomy. Bx-positive patients tend to have more frequent residual tumor in lymph nodes. The utility of PCEB in predicting residual cancer in the lymph nodes needs to be explored further along with molecular predictors of response to preoperative therapy.

Spine needle biopsy simulator using visual and force feedback.

OBJECTIVE: Biopsy with an inserted needle is an important procedure for lesion detection in the spine, but is difficult to perform due to the presence of many critical organs near the spine. This article presents a spine needle biopsy simulator, based on visual and force feedback, which can be used to plan the optimal path of a needle and to practice the procedure without risk. MATERIALS AND METHODS: The simulator is composed of a 3D human model, a visual-feedback component, a force-feedback component, and an evaluation module. The human model is based on 3D CT data. The visual-feedback component provides an oblique section, multiplanar reformatting images, and a volume-rendered image. Of these, the oblique section display is very useful for planning a 3D path for the needle. During simulation, the force-feedback component generates and provides realistic forces acting on the biopsy needle in real time by synchronizing them to visual feedback. After each simulation, the evaluation module provides a performance analysis for the trainee. RESULTS: For an XCT abdomen volume data set of 256 x 256 x 256, the update rate of image rendering due to needle movement is over 25 Hz, with a force-feedback rate of 1 kHz. This performance proved to be good enough for the trainee to learn the relationship between visual and force feedback. CONCLUSIONS: The simulator is useful for the planning of and training in complicated 3D spine needle biopsy procedures. It may be used as an educational tool for beginners, a practice tool to increase expertise, or a test bed for new procedures.

Elective groin irradiation is not indicated for patients with adenocarcinoma of the rectum extending to the anal canal.

PURPOSE: To evaluate the inguinal nodal failure rate in patients with locally advanced rectal cancer with anal canal involvement (ACI) treated with pelvic chemoradiation without elective inguinal irradiation. METHODS AND MATERIALS: From 1990 and 1998, 536 patients received preoperative or postoperative chemoradiation for rectal cancer with curative intent; 186 patients had ACI (<4 cm from the anal verge on rigid proctoscopy). Two patients had positive inguinal nodes at presentation. Chemoradiation was delivered preoperatively (45 Gy in 25 fraction) or postoperatively (53 Gy in 29 fractions) with concurrent continuous infusion of 5-fluorouracil (300 mg/m2/d). The inguinal region was specifically irradiated in only 2 patients who had documented inguinal nodal disease. RESULTS: The median follow-up was 50 months. Only 6 of 184 ACI patients who had clinically negative inguinal nodes at presentation developed inguinal nodal recurrence (5-year actuarial rate 4%); 4 of the 6 cases were isolated. Two patients underwent successful salvage. Only 1 died of uncontrolled groin disease. Local control was achieved in both patients with inguinal nodal disease at presentation, but both died of metastatic disease. Only 3 patients with tumors >4 cm from the verge developed inguinal recurrence (5-year actuarial rate <1%). CONCLUSIONS: Inguinal nodal failure in rectal cancer patients with ACI treated with neoadjuvant or adjuvant chemoradiation is not high enough to justify routine elective groin irradiation.

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation.

The incidence, characteristics, risk factors for, and impact of chronic graft-vs-host disease (GVHD) were evaluated in a consecutive series of 116 evaluable HLA-identical blood stem cell transplant recipients. Minimum follow-up was 18 months. Limited chronic GVHD occurred in 6% (95% confidence interval [CI], 0%-13%), and clinical extensive chronic GVHD in 71% (95% CI, 61%-80%). The cumulative incidence was 57% (95% CI, 48%-66%). In univariate analyses, GVHD prophylaxis other than tacrolimus and methotrexate, prior grades 2 to 4 acute GVHD, use of corticosteroids on day 100, and total nucleated cell dose were significant risk factors for clinical extensive chronic GVHD. On multivariate analysis, GVHD prophylaxis with tacrolimus and methotrexate was associated with a reduced risk of chronic GVHD (hazard ratio [HR], 0.35; P =.001), whereas the risk was increased with prior acute GVHD (HR, 1.67; P =.046). When adjusted for disease status at the time of transplantation, high-risk chronic GVHD had an adverse impact on overall mortality (HR, 6.6; P <.001) and treatment failure (HR, 5.2; P <.001) at 18 months. It was concluded that there is a substantial rate of chronic GVHD after HLA-identical allogeneic blood stem cell transplantation, that clinical factors may alter the risk of chronic GVHD, and that high-risk chronic GVHD adversely affects outcome.