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Results for “multimodal integration”

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PubMed1996

Intraoperative radiation therapy in integrated treatment of rectal cancers. Results of phase II study.

PURPOSE: Risk of local recurrence of rectal cancer remains high despite extensive therapeutic strategies, many of which have been tried to achieve better local control (i.e., external beam radiation therapy (EBRT)). Recently, intraoperative radiation therapy (IORT) has been introduced in clinical protocols to boost the areas at risk of local recurrence. METHODS: Between April 1990 and December 1995, 44 patients with "high risk" (T3,N0-2 primary tumors) extraperitoneal rectal tumors and 24 patients with "locally advanced" (2 T3,N3 and 11 T4,N0-3 primary tumors; 11 local recurrences) tumors entered a protocol that included preoperative EBRT (38 Gy), surgery plus IORT (10 Gy) in the high-risk group, and preoperative EBRT (45-48 Gy) and concomitant computerized tomography (5-fluorouracil plus mitomycin C), surgery plus IORT (10-15 Gy), and postoperative adjuvant computerized tomography (5-fluorouracil plus folinic acid) in the locally advanced group. RESULTS: In the high-risk group, acute Grade 3 (Radiation Therapy Oncology Group scale) skin toxicity, attributable to preoperative treatment, involved one patient (2.2 percent); among locally advanced cases, Grade 3 hematologic toxicity was observed in one patient (4.1 percent). Treatment was discontinued in no patients. On average, IORT prolonged surgery by 48 minutes. There was no mortality. Four anastomotic leakages, one pelvic infection, and five wound infections were observed. No chronic IORT-related toxicity occurred. After mean follow-up periods of 28.3 and 25.9 months, 41 and 15 patients in the high-risk and locally advanced groups, respectively, are alive and disease-free. In one high-risk patient, an anastomotic recurrence occurred. In four patients with locally advanced tumors (1 T4 primary, 3 local recurrences) an unresectable tumor relapse developed locally. Distant metastases occurred in two high-risk patients and in eight patients with a locally advanced tumor. Three-year actuarial survival was 100 percent in both high-risk and locally advanced primary tumors and 68.2 percent in local recurrences. CONCLUSIONS: Results of this study suggest that multimodal treatment (including IORT) in rectal cancer is safe, has no significant increase of mortality and morbidity, and also shows a trend for local improvement. A longer term follow-up and larger numbers of patients could demonstrate the therapeutic efficacy of IORT in rectal cancer.

Antimetabolites, Antineoplastic↗

PubMed1997

[Exchange of medical imaging and data information in radiotherapy: needs, methods and current limits].

Extension of the image network within radiotherapy departments provides the technical infrastructure which is made necessary by the rapid evolution of techniques in the field of diagnosis and treatment in radiotherapy. The system is aimed at managing the whole set of data (textual data and images) that are needed for planning and control of treatments. The radiotherapy network addresses two objectives: managing both the information necessary for treatment planning (target volumes definition, planning dosimetry) and the control of all parameters involved during the patient's treatment under the treatment unit. The major challenge is to improve the quality of treatment. Multimodal imaging is a major advance as it allows the use of new dosimetry and simulation techniques. The need for standards to exchange medical imaging information is now recognized by all the institutions and a majority of users and manufacturers. It is widely accepted that the lack of standard has been one of the fundamental obstacles in the deployment of operational "Picture Archiving Communication Systems". The International Standard Organisation Open System Interconnection model is the standard reference mode used to describe network protocols. The network is based on the Ethernet and TCP/IP protocol that provides the means to interconnect imaging devices and workstations dedicated to specific image processing or machines used in radiotherapy. The network uses Ethernet cabled on twisted-pair (10 BaseT) or optical fibres in a star-shaped physical layout. Dicom V3.0 supports fundamental network interactions: transfer of images (computerized tomography magnetic resonance imaging query and retrieve of images), printing on network attached cameras, support of HIS/RIS related interfacing and image management. The supplement to the Dicom standard, Dicom RT, specifies five data objects known in Dicom as Information Object Definition for relevant radiotherapy. Dicom RT objects can provide a mean for standardized transfer of most of the information wich circulates in a radiotherapy department. A wide range of device types are represented, (treatment planning systems, portal imaging devices, linear accelerators, recording and verifying systems, conventional and virtual simulators). There will be additions and perhaps new developments in dataflow management, more complete integration with HIS/RIS system and printing, but the lion's share of the work has now been done. A project to integrate some security features into the Dicom protocol has begun.

Computer Communication Networks↗

PubMed2025

MedImg: An Integrated Database for Public Medical Images.

The advancements in deep learning algorithms for medical image analysis have garnered significant attention in recent years. While several studies have shown promising results, with models achieving or even surpassing human performance, translating these advancements into clinical practice is still accompanied by various challenges. A primary obstacle lies in the availability of large-scale, well-characterized datasets for validating the generalization of approaches. To address this challenge, we curated a diverse collection of medical image datasets from multiple public sources, containing 105 datasets and a total of 1,995,671 images. These images span 14 modalities, including X-ray, computed tomography, magnetic resonance imaging, optical coherence tomography, ultrasound, and endoscopy, and originate from 13 organs, such as the lung, brain, eye, and heart. Subsequently, we constructed an online database, MedImg, which incorporates and systematically organizes these medical images to facilitate data accessibility. MedImg serves as an intuitive and open-access platform for facilitating research in deep learning-based medical image analysis, accessible at https://www.cuilab.cn/medimg/.

Humans↗

PubMed1999

The role of higher-order motor areas in voluntary movement as revealed by high-resolution EEG and fMRI.

In the human motor cortex structural and functional differences separate motor areas related to motor output from areas essentially involved in higher-order motor control. Little is known about the function of these higher-order motor areas during simple voluntary movement. We examined a simple finger flexion movement in six healthy subjects using a novel brain-imaging approach, integrating high-resolution EEG with the individual structural and functional MRI. Electrical source reconstruction was performed in respect to the individual brain morphology from MRI. Highly converging results from EEG and fMRI were obtained for both executive and higher-order motor areas. All subjects showed activation of the primary motor area (MI) and of the frontal medial wall motor areas. Two different types of medial wall activation were observed with both methods: Four of the subjects showed an anterior type of activation, and two of the subjects a posterior type of activation. In the former, activity started in the anterior cingulate motor area (CMA) and subsequently shifted its focus to the intermediate supplementary motor area (SMA). Approximately 120 ms before the movement started, the intermediate SMA showed a drop of source strength, and simultaneously MI showed an increase of source strength. In the posterior type, activation was restricted to the posterior SMA. Further, three of the subjects investigated showed activation in the inferior parietal lobe (IPL) starting during early movement preparation. In all subjects showing activation of higher-order motor areas (anterior CMA, intermediate SMA, IPL) these areas became active before the executive motor areas (MI and posterior SMA). We suggest that the early activation of the anterior CMA and the IPL may be related to attentional functions of these areas. Further, we argue that the intermediate part of the SMA triggers the actual motor act via the release of inhibition of the primary motor area. Our results demonstrate that a noninvasive, multimodal brain imaging technique can reveal individual cortical brain activity with high temporal and spatial resolution, independent of a priori physiological assumptions.

Adult↗

PubMed1984

Positron emission tomography in the study of human tumors.

To increase our understanding of cancer and improve cancer treatment on a rational basis we need to identify both qualitative and quantitative differences between normal and neoplastic tissue. The multimodality approach to cancer treatment includes radiotherapy, chemotherapy, hyperthermia, and immunotherapy. Most of the data on which we base our therapeutic strategies have been derived from in vitro studies or animal tumor models. More information is required on the physiology of in vivo human tumors and their response to therapy. Positron emission tomography allows the regional tissue concentration of a positron emitting radionuclide to be measured in absolute units. If valid tracer models can be formulated that accurately describe the fate of an administered "biological" tracer then the physiological process under investigation can be measured quantitatively. The sequential inhalation of C15O2, 15O2, and 11CO allows regional tissue blood flow, oxygen utilization and blood volume to be measured in absolute units. Tissue perfusion, a measure of nutrient (eg, oxygen) supply, drug delivery, or a means of heat dissipation, is of immense importance to oncologists. The oxygen-15 technique has been used not only to study regional blood flow and oxygen utilization in both tumor and normal tissue but also their response to therapeutic intervention. In those studies were tracer models are thought to be less than complete (eg, due to insufficient biological data) then only a semiquantitative or qualitative assessment of the pathophysiological state may be possible. In this respect, tumor function has been characterized by the rate of uptake of 18F-2-deoxyglucose. This technique has provided a means of tumor grading and differentiating between radiation-induced tissue necrosis and tumor recurrence. Metabolic imaging with labeled amino acids appears particularly useful in the delineation of tumor extent. Blood brain barrier integrity and the pharmacokinetics of cytotoxic drugs have also been studied quantitatively. In the future, receptor studies are likely to play an increasing role. In this review dealing with the positron emission tomography oncologic work to date, emphasis has been placed on the physiological information obtainable and how it may further our understanding of cancer and its treatment.

Blood-Brain Barrier↗

PubMed2006

Maximized combined modality treatment of an unselected population of oral and oropharyngeal cancer patients. Final results of a pilot study compared with a treatment-dependent prognosis index.

BACKGROUND: In an attempt to raise the survival of an unselected and representative population of oral and oropharyngeal squamous cell cancer patients, a pilot study of an integrated four-modality treatment was conceived. Final endpoints were compliance, loco-regional control, survival (after complete 5-year follow-up), and a concept of trial assessment using the treatment-dependent prognostic index TPI. PATIENTS: Eighty-seven consecutive patients with histologically proven untreated stages I-IV disease presented in the period between 1997 and 1999 of whom 14 had to be considered uncurable and 73 were fit to be treated with the intention of achieving a cure. METHODS: All patients received one cycle of neoadjuvant intraarterial chemotherapy with 150 mg/m(2) cisplatin (systemically neutralized with sodium thiosulphate), and, if possible, by consecutive treatment applying both surgery of the primary tumour and the neck lymphatics, as well as by adjuvant radiation over 5 weeks (51.3 Gy) plus concurrent chemotherapy (weekly systemic docetaxel 25 mg/m(2)). RESULTS: Ninety per cent of all cases and 96% of the patients treated with curative intention received more than one modality due to study design. Patient non-compliance in the group treated with curative intention has been 18/73 (=25%), and protocol compliance has been 32/73 (=44%). The locoregional control rate for all cases was 71% (62/87 patients) and for the patients treated with curative intention 83.5% (61/73 patients). Thirteen/fourteen non-curable patients died after a mean period of 4 months. After a median observation time of 5 years, the final absolute survival of the unselected population was 53%, and of the patients treated with curative intention 62% (especially, 70% and 50% for patients with operable stages III and IV, respectively). CONCLUSION: The multimodality regimen as presented proved feasible and showed high objective and relative survival rates in comparison with known data from tumour registries of unselected populations. Intra-arterial chemotherapy should be considered a valuable addition to treatment. The potential of survival benefit from this multimodality regimen in comparison with the prognosis index TPI should be investigated in further studies.

Adult↗

PubMed1995

Applied physiology of triathlon.

The triathlon is a 3-event endurance sport in which athletes compete sequentially in swimming, cycling and running. The primary determinant of success is the ability to sustain a high rate of energy expenditure for prolonged periods of time. Exercise training-induced physiological adaptations in virtually all systems of the body allow the athlete to accomplish this. Aerobic capacity (measured as maximal oxygen uptake, VO2max), economy of motion (submaximal VO2) and fractional utilisation of maximal capacity (%VO2max) reflect the integrated responses of these physiological adaptations. Numerous studies have reported relatively high mean VO2max values for various groups of triathletes that are comparable to those reported for athletes in single-event endurance sports and clearly above those reported for untrained individuals. In shorter distance triathlons and in studies using recreational (rather than elite) triathletes, VO2max is related to performance in the corresponding event of the triathlon (e.g. tethered swimming VO2max with swim time). In longer events and with more elite triathletes, VO2max correlates less well with performance. The physiological adaptations that correspond to and facilitate improved VO2max occur centrally in the cardiovascular system, centred on increased maximal cardiac output, and peripherally in the metabolic systems, centred around increased arterio-venous O2 (a-v O2) difference. While a high VO2max in individuals is clearly of importance to triathlon performance, energy output must be sustained for long periods of time, making economy of motion also very important. Studies suggests that competitive swimmers have better swimming economy than triathletes. However, since many triathletes have previously been competitive swimmers this finding is questionable. The finding suggests that triathletes from nonswimming backgrounds would benefit from improving swimming technique rather than concentrating training workouts solely on distance. In cycling and running, comparison studies have not been done. Economy of motion in swimming, cycling and running have all been found to be correlated with comparable event performance. Training to improve swimming economy can be done without prior exercise, but training to improve swimming economy can be done without prior exercise, but training to improve cycling and running economy should take the multimode nature of a triathlon into consideration. That is, swimming should precede cycling economy training, and cycling should precede running economy training. Cardiovascular, metabolic and neuromuscular adaptations are the main physiological correlates of improved movement economy. Since exercise-induced stress on most physiological systems is based on relative, rather than absolute, exercise intensity, training and racing intensities are frequently quantified as a percentage of maximal capacity of %VO2max.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

PubMed1998

The endovascular treatment of brain arteriovenous malformations.

Advances in superselective microcatheterization techniques, which took place in the past decade, established superselective endovascular exploration as an integral and indispensable tool in the pretherapeutic evaluation of brain AVMs. The strict and routine application of superselective angiography furthered our knowledge on the angioarchitecture of brain AVMs, including vascular composition of the nidus, types of feeding arteries and types and patterns of venous drainage. In addition, various types of weak angioarchitectural elements, such as flow-related aneurysms, intranidal vascular cavities and varix formation proximal to high-grade stenosis of draining veins, could be identified as factors predisposing for AVM rupture. A wide spectrum of secondary angiomorphological changes induced by the arteriovenous shunt of the nidus and occurring up- and downstream of the nidus have been identified as manifestations of high-flow angiopathy. These data help to better predict the natural history, understand the widely variable clinical presentation and to define therapeutic targets of brain AVMs. Correlation of the topography of the AVM as demonstrated by MR with the angioarchitecture as demonstrated by superselective angiography provided a system for topographic-vascular classification of brain AVMs, which proved very useful for patient selection and definition of therapeutic goals. This study showed, that 40% of patients with brain AVMs can be cured by embolization alone with a severe morbidity of 1.3% and a mortality of 1.3%. Part of theses patients can, however, be cured equally effective by microsurgery or radiosurgery. Which modality will be chosen for a particular patient will mainly depend on the locally available expertise and experience, but also on the preference of the patient following its comprehensive information about the chances for cure and the risks associated with each of these therapeutic modalities. Embolization has a significant role in the multimodality treatment of brain AVMs, by either enabling or facilitating subsequent microsurgical or radiosurgical treatment. Appropriately targeted embolization in otherwise untreatable AVMs represents a reasonable form of palliative treatment of either ameliorating the clinical condition of the patient or reducing the potential risk of hemorrhage. Regarding the practical aspects of the endovascular treatment the following conclusions could be drawn from the experience obtained with this series of 387 patients with a brain AVM: (1) The goal of endovascular treatment should be defined prior to the procedure. This does not preclude a change in the goal, if additional information obtained during the procedure make this necessary. (2) The result of endovascular treatment of a brain AVM in terms of the degree of obliteration achieved and complication rate depends mainly on the endovascular strategy developed and the technique applied. These depend on the specific angioarchitecture and topography of the individual AVM, on the past history and clinical presentation of the patient and on the predefined goal of embolization. The strategy should include the definition of embolization targets, the selection of the most appropriate approach for endovascular navigation, the determination of the sequence of catheterization of individual feeding arteries, the selection of the type of catheters and microcatheters, the selection of the appropriate embolic materials as well as the site and mode of their delivery. Thereafter, every endovascular move should be, as in a chess game, the result of a logical plan. (3) Atraumatic superselective microcatheterization is a key point in the endovascular treatment of brain AVMs. It requires manual skills, knowledge of anatomy and respect for the vascular wall. (4) All locations of brain AVMs should be regarded as eloquent, and no distinction should be made between eloquent and non-eloquent areas of the brain when deciding on the execution of embolizatio

Adolescent↗

PubMed1992

Efficacy of automatic multimodal device therapy for ventricular tachyarrhythmias as delivered by a new implantable pacing cardioverter-defibrillator. Results of a European multicenter study of 102 implants.

BACKGROUND: Third-generation implantable cardioverter-defibrillators are devices designed to treat ventricular tachycardia (VT) and ventricular fibrillation (VF) by means of overdrive pacing, cardioversion, or defibrillation. So far, the efficacy of tiered therapy has been documented only in small series. Therefore, a European multicenter clinical evaluation study of a new tachyarrhythmia control device, the Medtronic PCD pacer-cardioverter-defibrillator with epicardial patch-lead configuration, was undertaken. METHODS AND RESULTS: We report on 102 patients (mean age, 55 +/- 13 years) from 11 European centers. PCD devices implanted between May 1989 and February 1991 were included. The patients suffered from hemodynamically significant ventricular tachyarrhythmias not suppressed by antiarrhythmic drug therapy and unrelated to acute myocardial infarction; one patient had nonsustained VT and severely depressed left ventricular function. Seventy patients had coronary artery disease with old myocardial infarctions, 23 had cardiomyopathies of various etiologies, and nine patients had no detectable heart disease. Mean ejection fraction was 36 +/- 14% (range, 10-76%). Mean intraoperative defibrillation threshold (51 patients) was 10.6 +/- 5.1 J (range, 2-18 J). The documented follow-up ranged from 1 to 21 months (mean, 9.4 +/- 5.8 months), or 79.9 cumulative patient-years. Perioperative mortality was 3.9%. The actuarial survival rate at 12 months was 91%. One sudden arrhythmic death occurred. Sixty patients (58%) received device therapy. Seventeen patients had therapies only for "VF" episodes, 16 patients only for VT, and 28 patients for VT and "VF" episodes. Based on device memory data, 1,235 spontaneous VT episodes were detected and treated in 43 patients. Twelve hundred four of these VT episodes received painless initial antitachycardia pacing therapy, restoring sinus rhythm in 91%. The 108 ongoing episodes received 209 multiple therapeutic attempts. Eighty-five additional overdrive pacing therapies restored sinus rhythm in 30%. Initial ineffective antitachycardia pacing therapies received 51 cardioversion pulses. The success rate was 61%. Seventy-three additional cardioversion pulses were delivered to backup ineffective pacing therapy as well as ineffective secondary cardioversion pulses. Their success rate was only 40%. Two hundred eighty-six spontaneous episodes were detected in 44 patients as "VF." Overall defibrillation efficacy was 97.6%. CONCLUSIONS: The implanted device nearly eliminates sudden arrhythmic death in patients with documented, potentially fatal ventricular tachyarrhythmias. Automatic tiered therapy is highly effective to restore sinus rhythm, provided that an integrated two-zone tachycardia detection algorithm is used, assigning lower tachycardia rates to overdrive pacing and/or cardioversion and higher tachycardia rates to defibrillation. In general, spontaneous VTs can be terminated by automatic overdrive pacing, and painful or disturbing countershock therapies are not required to terminate the majority of spontaneous VT episodes.

Death, Sudden, Cardiac↗

PubMed2006

Combining EEG and fMRI: a multimodal tool for epilepsy research.

Patients with epilepsy often present in their electroencephalogram (EEG) short electrical potentials (spikes or spike-wave bursts) that are not accompanied by clinical manifestations but are of important diagnostic significance. They result from a population of abnormally hyperactive and hypersynchronous neurons. It is not easy to determine the location of the cerebral generators and the other brain regions that may be involved as a result of this abnormal activity. The possibility to combine EEG recording with functional MRI (fMRI) scanning opens the opportunity to uncover the regions of the brain showing changes in the fMRI signal in response to epileptic spikes seen in the EEG. These regions are presumably involved in the abnormal neuronal activity at the origin of epileptic discharges. This paper reviews the methodology involved in performing such studies, particularly the challenge of recording a good quality EEG inside the MR scanner while scanning is taking place, and the methods required for the statistical analysis of the combined EEG and fMRI time series. We review the results obtained in patients with different types of epileptic disorders and discuss the difficult theoretical problems raised by the interpretation of an increase (activation) and decrease (deactivation) in blood oxygen level dependent (BOLD) signal, both frequently seen in response to spikes.

Biomedical Research↗

PubMed2026

Distinct cellular phenotypes of language and executive decline in amyotrophic lateral sclerosis.

Cognitive manifestations, including impairments in language and executive functions, are seen in amyotrophic lateral sclerosis (ALS), but the underlying mechanisms remain unclear. We mapped prefrontal cortex regions from ALS patients by integrating spatial and single-nucleus transcriptomics in a cognitively stratified patient cohort. We uncover that cognitive impairment in ALS is associated with distinct patterns of neuronal dysfunction and glial-vascular dysregulation that vary by region and cognitive subtype. Executive dysfunction is linked to reduced mitochondrial and synaptic activity in deep-layer dorsolateral prefrontal cortex neurons, whereas language-related deficits track with a diffuse pan-regional response involving glial and vascular abnormalities. Our analyses, validated by multiplexed imaging, further identify signatures in the prefrontal cortex that span both motor and cognitive phenotypes, including a multicellular gliosis response. The findings reveal that clinical heterogeneity in ALS is driven by phenotype-specific cellular interactions in motor and non-motor regions of the brain.

Amyotrophic Lateral Sclerosis↗

PubMed2006

Task-based imaging of colon cancer in the Apc(Min/+) mouse model.

Optical coherence tomography (OCT), laser-induced fluorescence (LIF), and laser-scanning confocal microscopy (LSCM) were used for the task of multimodal study of healthy and adenomatous mouse colon. The results from each modality were compared with histology, which served as the gold standard. The Apc(Min/+) genetic mouse model of colon cancer was compared with wild-type mice. In addition, a special diet was used for the task of studying the origins of a 680 nm autofluorescent signal that was previously observed in colon. The study found close agreement among each of the modalities and with histology. All four modalities were capable of identifying diseased tissue accurately. The OCT and LSCM images provided complementary structural information about the tissue, while the autofluorescence signal measured by LIF and LSCM provided biochemical information. OCT and LIF were performed in vivo and nondestructively, while the LSCM and histology required extraction of the tissue. The magnitude of the 680 nm signal correlates with chlorophyll content in the mouse diet, suggesting that the autofluorescent compound is a dietary metabolite.

Adenomatous Polyposis Coli Protein↗

PubMed2004

Combination of hyperbolic functions for multimodal biometrics data fusion.

In this paper, we treat the problem of combining fingerprint and speech biometric decisions as a classifier fusion problem. By exploiting the specialist capabilities of each classifier, a combined classifier may yield results which would not be possible in a single classifier. The Feedforward Neural Network provides a natural choice for such data fusion as it has been shown to be a universal approximator. However, the training process remains much to be a trial-and-error effort since no learning algorithm can guarantee convergence to optimal solution within finite iterations. In this work, we propose a network model to generate different combinations of the hyperbolic functions to achieve some approximation and classification properties. This is to circumvent the iterative training problem as seen in neural networks learning. In many decision data fusion applications, since individual classifiers or estimators to be combined would have attained a certain level of classification or approximation accuracy, this hyperbolic functions network can be used to combine these classifiers taking their decision outputs as the inputs to the network. The proposed hyperbolic functions network model is first applied to a function approximation problem to illustrate its approximation capability. This is followed by some case studies on pattern classification problems. The model is finally applied to combine the fingerprint and speaker verification decisions which show either better or comparable results with respect to several commonly used methods.

Algorithms↗

PubMed2003

Optimising postoperative pain management in the ambulatory patient.

Over 60% of surgery is now performed in an ambulatory setting. Despite improved analgesics and sophisticated drug delivery systems, surveys indicate that over 80% of patients experience moderate to severe pain postoperatively. Inadequate postoperative pain relief can prolong recovery, precipitate or increase the duration of hospital stay, increase healthcare costs, and reduce patient satisfaction. Effective postoperative pain management involves a multimodal approach and the use of various drugs with different mechanisms of action. Local anaesthetics are widely administered in the ambulatory setting using techniques such as local injection, field block, regional nerve block or neuraxial block. Continuous wound infusion pumps may have great potential in an ambulatory setting. Regional anaesthesia (involving anaesthetising regional areas of the body, including single extremities, multiple extremities, the torso, and the face or jaw) allows surgery to be performed in a specific location, usually an extremity, without the use of general anaesthesia, and potentially with little or no sedation. Opioids remain an important component of any analgesic regimen in treating moderate to severe acute postoperative pain. However, the incorporation of non-opioids, local anaesthetics and regional techniques will enhance current postoperative analgesic regimens. The development of new modalities of treatment, such as patient controlled analgesia, and newer drugs, such as cyclo-oxygenase-2 inhibitors, provide additional choices for the practitioner. While there are different routes of administration for analgesics (e.g. oral, parenteral, intramuscular, transmucosal, transdermal and sublingual), oral delivery of medications has remained the mainstay for postoperative pain control. The oral route is effective, the simplest to use and typically the least expensive. The intravenous route has the advantages of a rapid onset of action and easier titratibility, and so is recommended for the treatment of acute pain.Non-pharmacological methods for the management of postoperative pain include acupuncture, electromagnetic millimetre waves, hypnosis and the use of music during surgery. However, further research of these techniques is warranted to elucidate their effectiveness in this indication. Pain is a multifactorial experience, not just a sensation. Emotion, perception and past experience all affect an individual's response to noxious stimuli. Improved postoperative pain control through innovation and creativity may improve compliance, ease of delivery, reduce length of hospital stay and improve patient satisfaction. Patient education, early diagnosis of symptoms and aggressive treatment of pain using an integrative approach, combining pharmacotherapy as well as complementary technique, should serve us well in dealing with this complex problem.

Ambulatory Surgical Procedures↗

PubMed2000

Fractionated, three-dimensional, planning-assisted proton-radiation therapy for orbital rhabdomyosarcoma: a novel technique.

PURPOSE: Most children with orbital rhabdomyosarcoma will survive their disease. However, conventional photon-radiation treatment, as part of multimodality therapy, results in varying degrees of long-term functional and cosmetic side effects. This report introduces external beam proton radiation therapy (PRT) as a conformal, three-dimensional planned radiation technique for this disease, analyzes normal tissue dosimetry, and describes the technique's application in the first 2 patients. MATERIAL AND METHODS: Between January 1995 and February 1996, 2 patients underwent PRT following biopsy and chemotherapy for orbital rhabdomyosarcoma. Fifty and 55 Cobalt Gray Equivalent (CGE) were delivered to the gross tumor volume and 40 CGE to clinical target volumes in both patients. A relative biologic effectiveness (RBE) of 1.1 was utilized to correlate proton dose calculations with CGE. To achieve dose conformity, a "patch technique" was utilized, where target regions were divided into segments, each treated by a separate proton field. Dose-volume histograms were obtained for target and nontarget regions, including lens, bony orbit, pituitary gland, optic chiasm, optic nerves, lacrimal gland, and ipsilateral frontal and temporal lobes. RESULTS: At 3.4 and 2.5 years after PRT, both patients are clinically and radiographically free of disease. Visual acuity remains excellent, without signs of cataract formation; pituitary function is normal; cosmetically, only mild enophthalmos is noticeable. Doses to 90%, 50%, and 5% of lens volume were kept at less than 1%, less than 2%, and less than 8%, respectively. Fifty percent of lacrimal gland volume received less than 36% of the prescribed dose and 50% of the volume of the optic chiasm, pituitary gland, and hypothalamus were restricted to less than 2%. Proton conformity to orbital contents resulted in between 9% and 36% of the prescribed dose reaching the ipsilateral temporal and frontal lobes immediately adjacent to bony orbit (5% volume). CONCLUSION: PRT can offer excellent sparing of lens and selected intraorbital and ocular normal structures, while maintaining conformal target-dose coverage. The steep dose gradient beyond the orbit minimizes irradiation of normal brain parenchyma, with almost complete sparing of the pituitary gland. Reduction of integral irradiation exposure of the periorbital region will, hopefully, reduce the risk of second malignancy later in life. Reduced radiation dose to specific organs in close proximity to, but not part of the target region promises improved functional outcome and better cosmesis for childhood cancer survivors.

Child↗

PubMed2006

Design issues and priorities in team and nonpharmacological arthritis care research.

Nonpharmacologic and team care research present unique design challenges. Nonpharmacologic care by nature is multifaceted and complex. Rarely do patients receive an intervention in isolation. The delivery of a single or group of interventions can be provided by one provider but is frequently provided by teams. Therefore, it is imperative that clinical researchers design studies that evaluate single and multimodal interventions as well as studies that best reproduce the team model of service delivery to accurately examine interventions. While it is well accepted that the research question drives the design, it is imperative to recognize that certain aspects of nonpharmacologic and team care restrict the implementation or effectiveness of specific design components. For example, as patients are required to actively engage in lifestyle changes, double-blinding cannot be employed. In addition, there is no accepted operational definition of team care in arthritis. It is important to keep in mind the characteristics of these interventions in the selection of a research design and develop strategies to best examine these interventions. Combining aspects of randomized controlled trials with qualitative methods is one technique to enrich data collected on these interventions. Certain features of pharmacovigilance studies may also serve as an alternative model. The use of national or regional registries for longterm clinical followup as seen in orthopedic surgery may prove to be applicable in the design of studies for evaluation of team care. Our article will discuss issues related to the design and synthesis of arthritis care research, and the role of patients in the design of clinical trials; describe collaborative international activities furthering team and nonpharmacological arthritis care research; and identify research activities that may influence future practice and the health of people with arthritis.

Arthritis↗

PubMed2001

Hippocampus as comparator: role of the two input and two output systems of the hippocampus in selection and registration of information.

Processing of multimodal sensory information by the morphological subdivisions of the hippocampus and its input and output structures was investigated in unanesthetized rabbits by extracellular recording of neuronal activity. Analysis shows principal differences between CA3 neurons with uniform multimodal, mainly inhibitory, rapidly habituating sensory responses, and CA1-subicular neurons, substantial parts of which have phasic reactions and patterned on-responses, depending on the characteristics of the stimuli. These differences result from the organization of the afferent inputs to CA1 and CA3. Analysis of neuronal responses in sources of hippocampal inputs, their electrical stimulation, and chronic disconnection show the greater functional significance of the brain-stem reticular input for tonic responses characteristic of CA3. This input signal before entering the hippocampus is additionally preprocessed at the MS-DB relay, where it becomes more uniform and frequency-modulated in the range of theta-rhythm. It is shown that the new sensory stimuli produce inhibitory reset, after which synchronized theta-modulation is triggered. Other stimuli, appearing at the background of the ongoing theta, do not evoke any responses of the hippocampal neurons. Thus, theta-modulation can be regarded as a mechanism of attention, which prolongs response to a selected stimulus and simultaneously protects its processing against interference. The cortical input of the hippocampus introduces highly differentiated information analyzed at the highest levels of the neocortex through the intermediary of the entorhinal cortex and presubiculum. However, only CA1-subiculum receives this information directly; before its entrance into CA3, it is additionally preprocessed at the FD relay, where the secondary simplification of signals occurs. As a result, CA3 receives by its two inputs (MS-DB and FD) messages just about the presence and level of input signals in each of them, and performs relatively simple functions of determination of match/mismatch of their weights. For this comparator system, the presence of signal only in the reticulo-septal input is equivalent to quality of novelty. The cortical signal appears with some delay, after its analysis in the neocortex and shaping in the prehippocampal structures; besides, it is gradually increased due to LTP-like incremental changes in PP and mossy fiber synapses. The CA3 neurons with potentiated synapses of cortical input do not respond to sensory stimuli; that is, the increased efficacy of the cortical signals can be regarded as "familiarity" of a signal, terminating the reactive state of the CA3 neurons. The integrity of both inputs is necessary for gradual habituation of sensory responses in the hippocampus. The output signals of CA3 following in the precommissural fornix to the output relay-LS nucleus and to the brain-stem structures have strong regulatory influence on the level of brain activity (arousal), which is an important condition for processing and registration of information. The primary targets of this output signal are raphe nuclei, which suppress activity of the ascending excitatory RF. In the background state, activity of the CA3 neurons through the intermediary of raphe keeps RF under tonic inhibitory control. Inhibition of the majority of CA3 pyramidal neurons during a novel stimulus action decreases the volume of its output signal to raphe and releases RF from tonic inhibition (increase in level of activity of the forebrain, arousal). When the responses of CA3 neurons habituate, the initial high background activity is reinstated, as well as tonic suppression of RF. Analysis of the second output of CA3 (by Schaffer's collaterals to CA1) shows that activity in this pathway can block access of cortical signals from PP to CA1 neurons by action upon the local system of inhibitory neurons, or by shunting the propagation of signals in apical dendrites. Thus, CA3 can act as a filter controlling the information transmission by CA1; such transmission at any given moment is allowed only in those CA1 neurons which receive SC from CA3 neurons, responding to the sensory stimulus by suppression of their activity. Disconnection of the CA3 output fibers results in disappearance of habituation in all its target structures (raphe, RF, CA1). The output signal of CA1-subiculum follows by postcommissural fornix to the chain of structures of the main limbic circuit: mammillary bodies (medial nucleus), anterior thalamic nuclei (mainly antero-ventral nucleus), and cingulate limbic cortex (mainly posterior area). In each of these links, the signal is additionally processed. Habituation is nearly absent in these structures; instead, st

Animals↗

PubMed2026

Cell-free DNA genomic and fragmentomic features for early outcome prediction in large B cell lymphoma.

Curative-intent immunochemotherapy fails in ∼30% of patients with large B cell lymphoma (LBCL), yet no validated molecular tool enables early identification of high-risk individuals to guide treatment intensification. Using shallow whole-genome sequencing (sWGS) of plasma cell-free DNA from 190 LBCL patients, we develop and validate the ACT score (aberrations, composition of fragments, and terminal motif analyses), a composite classifier integrating genomic and fragmentomic features from a single post-cycle-1 sample. ACT-positive patients have worse 2-year outcomes versus ACT-negative patients: time-to-progression 29% vs. 83% (hazard ratio [HR]: 4.4, 95% confidence interval [CI]: 1.9-10.0; p = 1.5 × 10-4) and overall survival 47% vs. 93% (HR: 8.7, 95% CI: 3.0-25.4; p = 1.8 × 10-6). The ACT score is independently prognostic of the International Prognostic Index, and their combination identifies the highest risk patients. Unlike mutation-based approaches, this assay requires neither tumor tissue, germline control, nor a baseline plasma sample. Built on open-source tools and sWGS, the ACT score offers a feasible, scalable strategy for early risk stratification in aggressive LBCL.

Humans↗