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[Multimodal treatment of colon cancer?].

Surgical therapy is still the basis of therapy of patients with colon carcinoma. Multimodal therapeutical concepts are presently applied as a therapeutical standard in the adjuvant therapy and increasingly in the systemic therapy of patients with primarily inoperable metastases of the liver to reach a secondary operability. Interdisciplinary multimodal therapeutical concepts are even accepted within the therapy of metastasized colon carcinomas. There are still unanswered questions regarding sequences of palliative systemic therapies and their combinations with local ablative methods.

Antineoplastic Agents↗

Combination of multimodal imaging and molecular genetic information to investigate complex psychiatric disorders.

Multimodal imaging, the combination of several brain imaging techniques in one subject, provides a wealth of parameters and favours the interpretation of complex models in schizophrenia research. Moreover, new imaging tools allow the investigation of distinct neurotransmitter systems and their modulation by pharmacological intervention. An important feature of multimodal imaging is the possibility to characterize the activation dependencies of different neurotransmitters and provide the experimental tool to test system models of brain function and dysfunction. The combination of measurement techniques with high temporal resolution (e. g. MEG, EEG) and high spatial resolution (e. g. fMRI) facilitate the understanding of local and global systems as well as time characteristics. Moreover, the association of imaging parameters with genetic variations of neurotransmitter systems allows the investigation of neurotransmitter activity and its role in the pathophysiology of schizophrenia. To overcome the limitations of standard statistical methods, new approaches in machine learning have to be adapted to handle multiple parameters obtained from brain imaging and genetic measurements.

Brain↗

[The multimodal integration, correlation and fusion of morphology and function: the methods and initial clinical applications].

Besides the pure visual diagnosis of morphology in comparison with function, digital multimodal image analysis is steadily gaining in importance. Digital image processing is used in integration, correlation and fusion of topographically identical image data. After defining these terms and describing the acquisition techniques and influence parameters, this article reviews the methods of multimodal image processing, with emphasis on correlation methods. It also gives a short description of special methods in nuclear medicine. The clinical part briefly reviews the clinical use as well as the progress achieved and the benefits expected for diagnostic applications.

Diagnostic Imaging↗

Childhood multiple sclerosis (MS): multimodal evoked potentials (EP) and magnetic resonance imaging (MRI) comparative study.

We compared the diagnostic sensitivity of magnetic resonance imaging (MRI) and evoked potential (EP) studies in a series of 19 children affected by clinically definite (16 cases) and laboratory supported (3 cases) multiple sclerosis (MS). MRI revealed abnormal areas consistent with demyelinating plaques in 18 out of 19 cases: multiple lesions in 16 and an isolated lesion in 2 cases. Abnormal areas were more frequently found in supratentorial regions than in other areas of the central nervous system. In all patients, the distribution, form and topography of the lesions were typical of MS and similar to those found in the adult form of the disease. Multimodal EP were abnormal in 16 out of 19 cases. Visual (VEP) and somatosensory evoked potentials (SEP) abnormalities were frequently asymptomatic and VEPs were particularly sensitive in ascertaining childhood MS. MRI was slightly more sensitive than multimodal EP in confirming the clinical diagnosis of childhood MS. However, in suspected or probable MS with normal MRI, VEPs and SEPs may contribute to the definition of clinical diagnosis because of their capacity to demonstrate asymptomatic involvement in central nervous system (CNS) the optic nerve and central somatosensory pathways).

Adolescent↗

Multistate multimode vibronic dynamics: entanglement of electronic and vibrational degrees of freedom in the benzene radical cation.

An earlier theoretical treatment of multimode and multistate vibronic coupling in the benzene radical cation [Koppel et al., J. Chem. Phys. 117, 2657 (2002)] is extended to investigate also the behavior of the nuclear degrees of freedom and to include additional electronic states. The five lowest doublet electronic states are considered which have been shown earlier to be all interconnected through a series of conical intersections of their potential-energy surfaces. In the most extensive calculations, they are all included simultaneously in the quantum dynamical calculations performed, which represent a system of unprecedented complexity treated in this way. The results are compared with various reduced-dimensionality treatments (i.e., employing reduced vibrational and electronic function spaces). The different temporal behavior of the various electronic populations is emphasized and traced to the different locations of the various seams of conical intersections: due to the coherent oscillations of the time-dependent wave packet this leads to an oscillatory behavior in some cases and to monotonous behavior in others. A seemingly irreversible behavior of the system dynamics in this strictly microscopic treatment is confirmed. The importance of this benchmark system to highlight complex, entangled multimode, and multistate vibronic dynamics is pointed out.

Journal Article↗

Endoscopic Nd:YAG laser with aggressive multimodality therapy for locally advanced esophageal cancer.

BACKGROUND: Laser therapy of esophageal carcinoma has been limited to management of malignant dysphagia. To investigate its cytoreductive potential, Nd:YAG laser tumor debulking was added to multimodality therapy. METHODS: From 1994-1998, 29 patients with advanced locoregional esophageal carcinoma were enrolled in a prospective experimental study of high-dose neoadjuvant chemoradiotherapy together with endoscopic Nd:YAG laser photoablation. Comparisons were made to a retrospective cohort of 31 patients treated from 1990 to 1994 who underwent similar neoadjuvant chemoradiotherapy without laser debulking. RESULTS: Laser dosage ranged from 3457 to 67,443 J (mean 21,832 [SD 16,999]) delivered in 1 to 6 (mean 2.6 [1.4]) treatment sessions. Actuarial analysis showed improved survival in the laser-treated group versus the reference group (30.1 months vs. 16.5 months; p = 0.047). Multivariable analysis of the impact of age, T-stage, N-stage, completion of neoadjuvant therapy, and laser debulking that included all patients in both treatment groups showed completion of therapy to be the most significant variable associated with survival. There were 3 complications related to laser therapy. Relief of dysphagia was achieved in 19 of 29 patients (66%) in the laser group versus 13 of 31 (42%) in the reference group. CONCLUSIONS: Malignant dysphagia may be more effectively treated by the addition of Nd:YAG laser therapy to aggressive multimodality therapy. Improved survival with the addition of laser debulking warrants longer follow-up and a prospective comparative trial.

Adult↗

Multimodal therapy including neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) for stage IIB to IV cervical cancer.

OBJECTIVE: The purpose of this study was to determine the survival rates and toxicity levels that are associated with multimodal therapy (including neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC]) in patients with stage IIB to IVB cervical cancer. STUDY DESIGN: We retrospectively reviewed the cases of 49 patients who were treated between 1989 and 1997 with neoadjuvant MVAC for advanced cervical cancer. RESULTS: The clinical response rate was 90% (27 partial responders, 17 complete responders). Grade 3 or greater toxicity was mostly limited to neutropenia; no deaths were attributed to MVAC. Combined therapy after MVAC included operation in 34 patients (69%) and radiation in 41 patients (84%). Twenty-one patients (43%) had <2 cm residual tumor at histologic evaluation. Pelvic control was achieved in 86% of patients. Five-year disease-specific survival for patients with stage III disease was 60%. CONCLUSION: For patients with advanced cervical cancer, neoadjuvant MVAC had a high response rate (90%) and an acceptable toxicity level. Compared with historic control subjects, multimodal treatment may be associated with improved rates of pelvic control.

Adult↗

Using multimodal ligands to influence network topology in silver(I) coordination polymers.

A range of Ag(I) one- and two-dimensional coordination frameworks has been prepared and structurally characterized by using the multimodal ligand 3,6-di-pyrazin-2-yl-(1,2,4,5)-tetrazine, which offers both monodentate and chelating binding sites. It is demonstrated that multimodal ligands can be used to prepare coordination frameworks with novel and unusual topologies and to influence the precise geometrical arrangement of both ligands and metal centers within such supramolecular arrays.

Binding Sites↗

New experimental apparatus for multimodal resonance imaging: initial EPRI and NMRI experimental results.

Electron paramagnetic resonance imaging (EPRI) is a recently developed imaging technique employed in the study of free radicals in living systems. A full understanding of many physiological and pathological processes involving free radicals has not yet been attempted. The reason for this is that whilst nuclear magnetic resonance imaging (NMRI) is able to generate very accurate images of soft tissues and organs, EPRI does not have this capability because of its sensitivity limitations and the large linewidths of paramagnetic probes. This work describes the development and optimization of a multimodal apparatus capable of performing both pulsed EPRI and NMRI experiments on the same sample. The instrument combines the possibilities offered by both techniques: the functional and biochemical information achieved with EPRI, and the high-resolution anatomical images generated by NMRI. At present, these experiments are performed by moving the sample from an EPRI spectrometer to an NMRI apparatus. Consequently, the acquisition times are very long and several problems arise in image reconstruction. On the other hand, a unique apparatus operating in the two modalities greatly reduces the acquisition times and makes it possible to relate accurately the observed distribution of electron spin density with the anatomical description of individual organs. The experiments are performed at 357 Gauss, corresponding to a resonance frequency of 1.52 MHz for NMR and 1 GHz for EPR. In the present work, a detailed description of the apparatus is reported, including the main magnet, the gradient assembly, the multimodal cavity and the transmitter and receiver systems. The preliminary experimental results obtained by this apparatus are presented.

Electron Spin Resonance Spectroscopy↗

Lanthanide-loaded liposomes for multimodality imaging and therapy.

UNLABELLED: Many advanced molecular imaging agents are currently being investigated preclinically. Especially, liposomes, have proven to be very promising carrier systems for diagnostic agents for use in single-photon emission computed tomography (SPECT) or magnetic resonance imaging (MRI), as well as for therapeutic agents to treat diseases such as cancer. In this study, nanosized liposomes were designed and labeled with the radionuclides, holmium-166 (both a beta- and gamma-emitter and also highly paramagnetic) or technetium-99m, and coloaded with paramagnetic gadolinium allowing multimodality SPECT and MR imaging and radionuclide therapy with one single agent. METHODS: Diethylenetriaminepentaacetic acid bisoctadecylamide (an amphiphilic molecule with a chelating group suitable for labeling with radionuclides) and gadoliniumacetylacetonate (GdAcAc) (a small lipophilic paramagnetic molecule) were incorporated in liposomes. The liposomes were characterized by measuring their mean size and size distribution, gadolinium content, and radiochemical stability after incubation in human serum at 37 degrees C. The MRI properties (in vitro) were determined by use of relaxivity measurements at 1.5 and 3.0 Tesla in order to evaluate their potency as imaging agents. RESULTS: The liposomes were successfully labeled with holmium-166, resulting in a high labeling efficiency (95% +/- 1%) and radiochemical stability (> 98% after 48 hours of incubation), and coloaded with GdAcAc. Labeling of liposomes with technetium-99m was somewhat less efficient (85% +/- 2%), although their radiochemical stability was sufficient (95% +/- 1% after 6 hours of incubation). MRI measurements showed that the incorporation of GdAcAc had a strong effect on the MRI relaxivity. CONCLUSIONS: The synthesized liposomes allow for multimodality imaging and therapy, which makes these new agents highly attractive for future applications.

Lanthanoid Series Elements↗

Reversal of neuromotor and cognitive dysfunction in an enriched environment combined with multimodal early onset stimulation after traumatic brain injury in rats.

This study was designed to investigate the additional benefits of a multimodal early onset stimulation (MEOS) paradigm when combined with enriched environment (EE) versus EE only and standard housing (SH) on the recovery after experimental traumatic brain injury (TBI). Male Sprague- Dawley rats were subjected to moderate lateral fluid percussion (LFP) brain injury (n = 40) or sham operation (n = 6). Thereafter, the injured and sham/EE + MEOS and EE only groups were placed into a complex EE consisting of tunnel-connected wide-bodied cages with various beddings, inclining platforms, and toys. Along with group living and environmental complexity, injured and sham/EE + MEOS animals were additionally exposed to a standardized paradigm of multimodal stimulation including auditory, visual, olfactory, and motor stimuli. In contrast, injured and sham/SH groups were housed individually without stimulation. A standardized composite neuroscore (NS) test was used to assess acute post-traumatic neuromotor deficits (24 h after injury) and recovery on days 7 and 15; recovery of cognitive function was assessed on days 11-15 using the Barnes maze. Neuromotor impairment was comparable in all injured animals at 24 h post-injury, but braininjured EE + MEOS rats performed significantly better than both brain-injured SH and EE groups when tested on post-injury days 7 and 15 (p = 0.004). Similarly, latencies to locate the hidden box under the Barnes maze platform were significantly shortened in EE + MEOS animals at day 15 (p = 0.003). These results indicate that the reversal of neuromotor and cognitive dysfunction after TBI can be substantially enhanced when MEOS is added to EE.

Acoustic Stimulation↗

Multimodal postoperative pain management.

PURPOSE: The mechanisms of persistent postoperative pain, rationale for multimodal pain therapy, and limitations of currently available analgesic agents and administration routes and techniques are described. SUMMARY: Persistent postoperative pain can cause long-term disability. It is the result of complex neurohormonal effects that can be prevented using preemptive analgesic therapy. Multimodal pain therapy can result in additive or synergistic analgesic effects and minimize adverse drug effects. Limitations of systemic opioid analgesics given by patient-controlled analgesia include adverse effects, a short duration of action, and nocturnal hypoxemia. Limitations of local anesthetics include unwanted motor blockade, which can interfere with postoperative mobilization and rehabilitation efforts. Inadvertent administration of analgesics into subarachnoid, subdural, or vascular spaces is a potential problem with the epidural route. Use of this route may be limited by the perioperative use of prophylactic anticoagulation. CONCLUSION: Research is needed to identify analgesic agents and administration techniques with greater efficacy and safety than those currently available.

Analgesics↗

MethylModes: computationally efficient detection of multimodal distributions in DNA methylation data.

SUMMARY: MethylModes is an R package and Shiny application to identify multimodal distributions in human DNA methylation at individual CpG sites. Multimodal distributions, which can be the result of nearby genetic variation, environmental exposures, or assay artifacts, are susceptible to confounding and important to identify for methylation analysis. MethylModes is easily incorporated into existing quality control pipelines of array-based DNA methylation data. The underlying algorithm uses kernel smoothing of probe-level data to locate the number and location of peaks. The algorithm can be parallelized across probes for efficient implementation at genome-scale. We provide a case study implementation of MethylModes in the Health and Retirement Study as well as the Airwave Health Monitoring Study. AVAILABILITY AND IMPLEMENTATION: MethylModes is available on GitHub at https://github.com/lutiffan/methylModes as an R package wrapping an R Shiny application. We include a toy dataset to validate installation. The codebase is also published on Zenodo at https://doi.org/10.5281/zenodo.17448517.

DNA Methylation↗

BriGHT: transcriptome-regularized multimodal neuroimaging for brain disorder prediction.

MOTIVATION: Hypergraph-based models for brain disorder prediction mainly adopt imaging-derived hypergraphs as propagation backbones. However, the entanglement of topology construction and feature propagation leaves regional representations weakly constrained by underlying biological organization, making them vulnerable to subject-specific variation and noise, particularly in heterogeneous multimodal settings. RESULTS: We present BriGHT, a Brain transcriptome-reGularized Hypergraph framework for mulTimodal disorder prediction. BriGHT employs a transcriptome-derived structural reference as a soft anchoring prior to regularize neuroimaging ROI embeddings, stabilizing representation geometry while preserving disease-relevant subject-specific variation. BriGHT further incorporates a reliability-aware fusion module to estimate subject-specific modality reliability from prediction confidence, cross-modal consistency, and decision certainty, enabling adaptive integration under heterogeneous modality quality. Experiments on three neuroimaging cohorts (ADNI, ADHD-200, REST-meta-MDD) and four modalities (VBM, fMRI, FDG, AV45) demonstrate that BriGHT consistently outperforms competing graph/hypergraph learning methods across six brain disorder prediction tasks. Perturbation analyses show that BriGHT benefits from the spatial correspondence between transcriptomic modules and imaging ROIs, rather than from arbitrary hypergraph regularization alone. Ablation and meta-analytic interpretability analyses support the contribution of transcriptomic anchoring and adaptive fusion to robust and biologically meaningful brain disorder prediction. AVAILABILITY: The software is publicly available at: https://github.com/Yaolab-fantastic/BriGHT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Journal Article↗

The effect of parent training in music and multimodal stimulation on parent-neonate interactions in the neonatal intensive care unit.

This study examined the effects of parent training in music and multimodal stimulation on the quantity and quality of parent-neonate interactions and the weight gain and length of hospitalization of premature and low birthweight (LBW) infants in a Neonatal Intensive Care Unit (NICU). Twenty sets of parents and premature LBW infants participated in the study. Parents in the experimental group (n = 10) received approximately one hour of instruction in appropriate uses of music, multimodal stimulation including massage techniques, and signs of infant overstimulation and techniques for its avoidance. Parent-neonate interactions, specifically parent actions and responses and infant stress and nonstress behaviors, were observed for subjects in both groups. Infant stress behaviors were significantly fewer and appropriateness of parent actions and responses were significantly greater for experimental infants and parents than for control subjects. Parents in the experimental group also self-reported spending significantly more time visiting in the NICU than did parents of control infants. In addition, length of hospitalization was shorter and average daily weight gain was greater for infants whose parents received training, although these differences were not significant. A one month, postdischarge follow-up showed little difference between experimental and control group parent-infant interactions in the home.

Adolescent↗

A multimodal approach to control postoperative pathophysiology and rehabilitation in patients undergoing abdominothoracic esophagectomy.

UNLABELLED: This two-armed study was designed to determine whether recovery after esophageal resection may be improved by introducing a new multimodal approach. For 8 mo after the new approach was introduced, all patients undergoing abdominothoracic esophageal resection were studied (Group 2; n = 42). For comparison, a retrospective analysis was also conducted using the data of all patients who had undergone this operation in the 8 mo before the introduction of the new regimen, when the traditional therapy was still in use (Group 1; n = 49). All patients received an epidural catheter at the level of T6-9 before the induction of general analgesia. Afterward, Group 1 patients were operated under general anesthesia. For postoperative pain relief, a mixture of bupivacaine 1.25 mg/mL and sufentanil 1 microg/mL was administered during 5 days without titration of the quality of analgesia. Patients in Group 2 received a preoperative bolus of 10-15 mL bupivacaine 2.5 mg/mL and 20-30 microg sufentanil. After sensory block up to T4 was confirmed, general anesthesia was introduced and intraoperatively combined with a continuous infusion of 5 mL/h of a solution containing bupivacaine 1.75 mg/mL and sufentanil 1 microg/mL. Postoperatively, the epidural infusion rate was adjusted to the need of the individual patients, who were able to administer themselves additional bolus doses of 2 mL with a lockout time of 20 min. Early tracheal extubation and forced mobilization were pursued to improve recovery. Demographic data of both groups were comparable. The pain relief of Group 2 patients was superior to that of patients in Group 1. The nitrogen balance of a subgroup of nine matched pairs of patients with comparable nutritional status was less negative in Group 2 patients on Postoperative Days 1 and 2. Patients in Group 2 were tracheally extubated earlier (mean 6.7 vs 25.1 h after admission to the intensive care unit [ICU]), mobilized earlier (mean 1.2 vs 2.0 days after surgery), discharged from the ICU earlier (mean 1.7 vs 4.0 days), and fulfilled criteria for discharge from the ICU (mean 1.8 vs 4.1 days) and from the intermediate care unit earlier (4.9 vs 6.4 days). We conclude that the multimodal approach may improve recovery and thus reduce costs after abdominothoracic esophageal resection. IMPLICATIONS: Analgesia and blockade of the perioperative stress response, combined with other aspects of postoperative therapy, may improve recovery after surgery. The intensive care unit stay after esophageal resection was reduced by a new regimen (thoracic epidural analgesia, early tracheal extubation, forced mobilization). This approach may influence the cost of major surgery.

Abdomen↗

Improved survival for hepatocellular cancer with combination surgery and multimodality treatment.

Forty-one hepatic resections for malignant hepatomas were done in 35 consecutive patients from August 1985 to 1990. Twenty-one patients presented initially with resectable lesions and underwent resection for curative intent. Fourteen patients initially presented with unresectable intrahepatic disease. These patients underwent combined radiation and chemotherapy. Radiation consisted of external beam in all patients and 131I-antiferritin in 10 patients. Greater than 50% tumor reduction was noted in all patients, and resection then was performed. Six patients recurred and were re-resected. Complications occurred in 15 patients (36%), with no difference between groups. There were no perioperative deaths. Five-year actuarial survival was 45% and 48% for resection and multimodality. The authors conclude that some patients with unresectable intrahepatic hepatoma may successfully be converted to resectable by multimodality radiation/chemotherapy. The survival of these patients is similar to that of primary resected patients. Further, multiple, sequential resections appear to significantly prolong survival and can be performed with an acceptable morbidity and mortality rates.

Actuarial Analysis↗

Multimodality monitoring in severe head injury.

PURPOSE OF REVIEW: This review describes recent advances in multimodal neuromonitoring of patients following severe head injury during the period from 2001 to 2002. RECENT FINDINGS: Monitoring intracranial pressure is considered a standard part of therapy despite a lack of randomized studies comparing patients with and without intracranial pressure monitoring. Jugular oximetry and brain tissue oxygen pressure monitoring are being used more frequently as part of a treatment protocol. Intracerebral microdialysis, despite the widespread use as a research tool, still cannot be considered a standard in clinical monitoring. These new monitoring devices may provide useful insight into the evolution of brain injury. SUMMARY: Technology is rapidly changing the nature of neuromonitoring. New devices are becoming available which make the monitoring truly multimodal. Studies are needed to determine how to best incorporate these new parameters into effective management protocols.

Journal Article↗