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PubMed2025

Multimodal CustOmics: A unified and interpretable multi-task deep learning framework for multimodal integrative data analysis in oncology.

Characterizing cancer presents a delicate challenge as it involves deciphering complex biological interactions within the tumor's microenvironment. Clinical trials often provide histology images and molecular profiling of tumors, which can help understand these interactions. Despite recent advances in representing multimodal data for weakly supervised tasks in the medical domain, achieving a coherent and interpretable fusion of whole slide images and multi-omics data is still a challenge. Each modality operates at distinct biological levels, introducing substantial correlations between and within data sources. In response to these challenges, we propose a novel deep-learning-based approach designed to represent multi-omics & histopathology data for precision medicine in a readily interpretable manner. While our approach demonstrates superior performance compared to state-of-the-art methods across multiple test cases, it also deals with incomplete and missing data in a robust manner. It extracts various scores characterizing the activity of each modality and their interactions at the pathway and gene levels. The strength of our method lies in its capacity to unravel pathway activation through multimodal relationships and to extend enrichment analysis to spatial data for supervised tasks. We showcase its predictive capacity and interpretation scores by extensively exploring multiple TCGA datasets and validation cohorts. The method opens new perspectives in understanding the complex relationships between multimodal pathological genomic data in different cancer types and is publicly available on Github.

Deep Learning↗
PubMed2002

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗
PubMed1999

Surgery and multimodal treatments in pancreatic cancer--a review on the basis of future multimodal treatment concepts.

BACKGROUND: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. In spite of several positive studies, and the fact that multimodality treatment is the standard concept in major centers for pancreatic cancer surgery, a recent trial shed some doubt on the positive effect of adjuvant radiochemotherapy, so that the majority with reservations about multimodal treatment feel confirmed in their opinion that surgical treatment alone is sufficient therapy for resectable pancreatic cancer. The controversy among those for and against adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. PATIENTS/METHODS: The literature on the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. A special view was concentrated on the biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities, to characterize the disease for an optimally targeted treatment in conjunction with surgical removal of the tumor. The results of systemic and regional chemotherapy and radiotherapy either alone or in combination, before, during, and after surgery, were critically analyzed with respect to the oncological possibilities and pitfalls of each treatment method. RESULTS: In two randomized trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy (Bakkevold), the adjuvant treatment achieved a significant prolongation of the median survival time. The 5- and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy, the survival times were improved vs. surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalizing margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. CONCLUSIONS: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being undecisive or against adjuvant therapy, the participation in trials, e.g., ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested vs. surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy.

Adenocarcinoma↗
PubMedDate not supplied

Multimodality paradigms for a healthy multimodality society.

The American Radium Society encourages the study of cancer in all its aspects, encourages liaison among the various medical specialists and allied scientists, and thereby champions multimodality oncologic care. Past and present membership rolls of the Society read like a "Who's Who" of cancer care and include distinguished physicians and allied scientists whose primary focus spans the spectrum of oncologic subspecialties; however, the current distribution of areas of expertise may not necessarily be optimal. Moreover, the practice of medicine constantly is changing, and we, as a society, should be prepared to evolve with it. For example, treatment of cancers arising in the head and neck region has changed dramatically during the past decade. The successful integration of concurrent chemotherapy with radiation therapy has created new paradigms for optimal care. These paradigms potentially decrease the risk of distant metastases, improve the local-regional control of disease, increase the likelihood of organ preservation, and reduce the risk posed by microscopic-sized unresected disease. Yet, much remains unknown, some of the available data appear contradictory, and much is left to do. Similar analysis persuasively argues that other groups that have specific expertise must also play a vital role in modern oncologic care, including radiation biologists, medical physicists, and molecular biologists. Yet, the current environment creates formidable obstacles to participation in the American Radium Society's mission. We must improve our understanding of these barriers and implement original solutions to ensure that our society remains in the forefront of progress in the fight against cancer. In particular, programs to increase the educational reach of the ARS need to be devised, implemented, and nurtured. The ARS has a long, proud history, but we should not seek to live in its past. We must seek continuously and welcome enthusiastically changes in the Society that will align the ARS with paradigms of cutting-edge oncologic care.

Combined Modality Therapy↗
PubMed1996

Importance of NMDA receptors for multimodal integration in the deep layers of the cat superior colliculus.

1. Many sensory events contain multimodal information, yet most sensory nuclei are devoted to the analysis of single-modality information. In the deep superior colliculus (DSC), visual, auditory, and somatosensory information converges on individual multimodal neurons. The responses of multimodal neurons are determined by the temporal and spatial correspondence properties of the converging inputs such that stimuli arising from the same event elicit a facilitated multimodal response. 2. N-methyl-D-aspartate (NMDA) receptors may underlie the detection of spatial and temporal coincidence and could be involved in the generation of multimodal facilitatory responses because of the nonlinear properties of NMDA-receptor-mediated events. To assess the role of NMDA receptors in multimodal integration, we made extracellular recordings from single multisensory neurons in the DSC of the cat. 3. The responses to visual, auditory, and somatosensory stimuli alone and to multimodal combinations of stimuli were challenged with iontophoretically applied D-2-amino-5-phosphonovalerate (AP5), an NMDA receptor antagonist. All responses to visual stimuli presented alone (n = 9) were greatly reduced. Somatosensory responses (n = 25) were usually decreased. In contrast, the responses to auditory stimulation were decreased (n = 9), unaffected (n = 3), or enhanced (n = 5). 4. Responses to multimodal stimulus presentations were consistently reduced during iontophoretic application of AP5, irrespective of the modalities that made up the stimulus. The reductions of multimodal responses were significantly greater than the sum of the reductions of responses to single-modality stimuli. 5. The data suggest that for unimodal stimuli, the importance of NMDA receptors in synaptic transmission of sensory responses in DSC may be dependent on the stimulus modality. Furthermore, NMDA receptors are of major importance in the integration of input from different modalities for the generation of multimodal responses.

2-Amino-5-phosphonovalerate↗
PubMed1996

A comparison of multimodal therapy and surgery for esophageal adenocarcinoma.

BACKGROUND: Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. METHODS: Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. RESULTS: Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P<0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P=0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P=0.01). CONCLUSIONS: Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.

Adenocarcinoma↗
PubMed2026

Survival prediction for clear cell renal cell carcinoma based on deep multimodal synergistic survival network.

Objective.To propose a deep multimodal synergistic survival analysis framework (Deep Multimodal Synergistic Survival Network, DMSSN) to achieve accurate prognostic analysis for clear cell renal cell carcinoma (ccRCC).Methods.This study (DMSSN) utilized matched multimodal data from the Cancer Genome Atlas-KIRC database, including CT imaging data, whole slide images, copy number variation (CNV) features, and clinical data. Deep Canonical Correlation Analysis was employed to map heterogeneous modalities into a shared latent space. Contrastive learning was introduced to enhance semantic consistency across multimodal features, and a gating network was utilized for the adaptive fusion of multimodal information to achieve precise survival risk prediction for patients.Results.Experimental results demonstrated that DMSSN achieved a Concordance Index (C-index) of 0.8153 &#xb1; 0.0994, with a Log-rank testp-value of 1.6553&#xd7;10-11. DMSSN exhibited significant performance advantages over traditional statistical methods like Log-rank-Cox (0.7055 &#xb1; 0.0670) and machine learning methods such as Random Survival Forest (RSF) (0.6836 &#xb1; 0.1048). Furthermore, in comparison with similar deep learning approaches, DMSSN outperformed late fusion strategies (0.7493 &#xb1; 0.1211) and discrete-time survival models such as DeepHit (0.7655 &#xb1; 0.1041) and Nnet-surv (0.7694 &#xb1; 0.0635). Notably, DMSSN still achieved the best predictive performance when compared to the classic deep survival model DeepSurv (0.7919 &#xb1; 0.0978) and advanced state-of-the-art multimodal fusion frameworks like Context-Aware Transformer (0.7735 &#xb1; 0.0818) and Multimodal Co-Attention Transformer (0.8102 &#xb1; 0.0972). Ablation studies showed that removing any single modality led to a decline in performance, with the largest numerical decrease occurring after removing CT imaging features (C-index decreased to 0.7327), validating the complementarity of multimodal data and the pivotal role of radiomic features in prognostic assessment. Module ablation experiments further confirmed the effectiveness of the core components.Conclusion:By effectively integrating imaging, pathology, genomic, and clinical features, the DMSSN framework demonstrates superior performance and robustness in the survival prediction of ccRCC.

Carcinoma, Renal Cell↗
PubMed1984

The incidence of metastases after multimodal therapy for cancer of the head and neck.

Combined therapeutic regimens integrating chemotherapy, radiation therapy, and surgery are reported to be effective in treating advanced squamous cell carcinomas of the head and neck. The current study evaluates 58 consecutive patients with advanced (T4, N3) head and neck cancers. Forty patients (multimodal group) were treated with 2 courses of chemotherapy (cisplatin 2 mg/kg; methotrexate 280-560 mg/m2 with leucovorin rescue; bleomycin 30 mu X 3) followed by radiation therapy and surgery. Eighteen patients (combined group) were treated with preoperative radiation therapy followed by surgery. In the multimodal group there were 27 (67.5%) partial responses and nine (22.5%) complete responses, for an overall response rate of 90%. Response rates by site of primary lesion were: oral cavity, 11 of 11; oropharynx, 13 of 17; hypopharynx, 5 of 5; and larynx 7 of 7. Distant metastases (skin, lung, bone, central nervous system [CNS]) appeared in 16 patients (40%) (P less than 0.05 versus combined) at a median time of 8.5 months after diagnosis, 15 in patients having a partial (11) or complete (4) response. Thirteen patients (33%) developed distant metastases within 1 year of diagnosis (P less than 0.05 versus combined). In 11 of these patients, the primary lesion and neck disease were resectable. Two thoracotomies were performed for solitary pulmonary metastases; one was resected for cure. Fifteen patients (38%) underwent curative resection; 11 (73%) were alive at 1 year, and ten (67%) were free of disease. Overall survival was 20 of 40 (50%) at 1 year. In the combined group, there were 14 partial responses (78%) and no complete responses. Early distant metastases appeared in two patients (12.5%), at 2 and 6 months after diagnosis. Seven patients (38%) underwent curative resection; six of seven (86%) were alive at 1 year, four of seven (57%) were disease-free. Six of 16 patients at risk (37.5%) survived 1 year. After combined therapy, six of ten patients (60%) with responses to therapy survived 1 year versus 12 of 20 responders (57%) without distant metastases in the multimodal group. It is concluded that multimodal therapy for advanced head and neck cancer results in a higher response rate than with conventional combined therapy. The incidence of early and postoperative distant metastases was increased after the multimodal regimen. At 1 year there were no differences in survival between the combined and multimodal groups for responders without early metastases. Further observation is needed to determine the net long-term effects of this regimen. A prospective randomized comparison of combined and multimodal therapy for advanced lesions is indicated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Binding of movement, sound and touch: multimodal coordination dynamics.

Very little is known about the coordination of movement in combination with stimuli such as sound and touch. The present research investigates the hypothesis that both the type of action (e.g., a flexion or extension movement) and the sensory modality (e.g., auditory or tactile) determine the stability of multimodal coordination. We performed a parametric study in which the ability to synchronize movement, touch and sound was explored over a broad range of stimulus frequencies or rates. As expected, synchronization of finger movement with external auditory and tactile stimuli was successfully established and maintained across all frequencies. In the key experimental conditions, participants were instructed to synchronize peak flexion of the index finger with touch and peak extension with sound (and vice-versa). In this situation, tactile and auditory stimuli were delivered counter-phase to each other. Two key effects were observed. First, switching between multimodal coordination patterns occurred, with transitions selecting one multimodal pattern (flexion with sound and extension with touch) more often than its partner. This finding indicates that the stability of multimodal coordination is influenced by both the type of action and the stimulus modality. Second, at higher rates, transitions from coherent to incoherent phase relations between touch, movement and sound occurred, attesting to the breakdown of multimodal coordination. Because timing errors in multimodal coordination were systematically altered when compared to unimodal control conditions we are led to consider the role played by time delays in multimodal coordination dynamics.

Auditory Perception↗
PubMed2001

Order-dependent timing of unimodal and multimodal stimulation affects prenatal auditory learning in bobwhite quail embryos.

This study examined the relationship between unimodal and multimodal sensory stimulation and their effects on prenatal auditory learning in bobwhite quail embryos. Embryos exposed to a maternal call in the 24 hr prior to hatching (unimodal condition) significantly preferred this familiar call over an unfamiliar call in postnatal testing, but failed to demonstrate this preference when the maternal call was presented concurrently with non-synchronized patterned light (multimodal condition). To further explore this interference effect, we provided one group of embryos concurrent exposure to a maternal call and patterned light for 12 hr followed by 12 hr exposure to the call alone (multimodal-->unimodal call). This group failed to prefer the familiar call during postnatal testing. In contrast, reversing the order of presentation during prenatal exposure (unimodal call-->multimodal) led a second group of subjects to significantly prefer the familiar call, suggesting that the order-dependent timing of sensory stimulation can significantly impact prenatal auditory learning. Experiment 3 examined the influence of modality versus timing of sensory stimulation on prenatal auditory learning by providing three groups of embryos with exposure to a maternal call during the 12 hr prior to hatching and by varying the duration of visual stimulation. Results indicate that 12 hr unimodal exposure to patterned light does not support prenatal auditory learning when it is followed by 12 hr exposure to multimodal stimulation (light-->multimodal), but can facilitate prenatal auditory learning when it is followed by unimodal exposure to the call alone (light-->call). Results are discussed in terms of intersensory relationships during perinatal development.

Acoustic Stimulation↗
PubMed1992

Efferent cortical connections of multimodal cortex of the superior temporal sulcus in the rhesus monkey.

The cortex of the upper bank of the superior temporal sulcus (STS) in the rhesus monkey contains a region that receives overlapping input from post-Rolandic sensory association areas and is considered multimodal in nature. We have used the fluorescence retrograde tracing technique in order to answer the question of whether multimodal areas of the STS project back to post-Rolandic sensory association areas. Additionally, we have attempted to answer the question of whether the projections from the multimodal areas directed to the parasensory association areas originate from common neurons via axon collaterals or from individual neurons. The results show that multimodal area TPO of the STS projects back to specific unimodal parasensory association areas of the parietal lobe (somatosensory), superior temporal gyrus (auditory), and posterior parahippocampal gyrus (visual). In addition, a substantial number of projections from area TPO are directed to distal parasensory association areas, area PG-Opt in the inferior parietal lobule, areas Ts1 and Ts2 in the rostral superior temporal gyrus, and areas TF and TL in the parahippocampal gyrus. These latter regions are themselves considered to be higher-order association areas. It was also noted that the majority of the projections to these higher-order association areas originate from the middle divisions of area TPO (TPO-2 and TPO-3). These neurons are organized in a significantly overlapping manner. Despite this overlap of the projection neurons, only an occasional double labeled neuron was observed in area TPO. Thus, our observations indicate that the multimodal region of the superior temporal sulcus has reciprocal connections with the unimodal parasensory association cortices subserving somatosensory, auditory and visual modalities, as well as with other post-Rolandic higher-order association areas. These connections from area TPO to post-Rolandic association areas may have a modulating influence on the sensory association input leading to multimodal areas in the superior temporal sulcus.

Animals↗
PubMed2003

Multimodality therapy including radiotherapy and chemotherapy improves event-free survival in stage C esthesioneuroblastoma.

BACKGROUND: To evaluate the efficacy of multimodality therapy in patients with esthesioneuroblastoma (ENB). PATIENTS AND METHODS: From 01/1979 through 08/2001, 47 patients with ENB (20 men, 27 women, age 5-81 years), were registered from 18 oncologic centers. There were 14 tumors stage B and 33 stage C according to the Kadish classification. Initial treatment included surgery alone in seven patients, radiotherapy (RT) with or without chemotherapy (CTX) in twelve, surgery plus postoperative RT in 15, and multimodality therapy (surgery plus pre- or postoperative CTX plus postoperative RT) in 13. RESULTS: The 5-year overall survival (OS) for the whole group was 64 +/- 8% and the 5-year event-free survival (EFS) 50 +/- 8%. Patients with multimodality treatment had a significantly better 5-year EFS (74 +/- 13%) compared to the other patients (41 +/- 9%; p = 0.05), while the 5-year OS was not significantly different between the treatment groups (p = 0.39). For patients with Kadish stage C, multimodality therapy (n = 11) resulted in superior 5-year EFS (72 +/- 14% vs 17 +/- 9%; p = 0.01). These patients tended to have an improved OS (69 +/- 15% vs 47 +/- 12%; p = 0.19) compared to the other treatment groups. None of the patients with multimodality treatment had a metastatic relapse. CONCLUSION: Multimodality treatment (surgery plus pre- or postoperative CTX plus postoperative RT) appears to be highly efficient in preventing local and systemic relapse in patients with advanced ENB. Timing and optimal agents of CTX need to be further evaluated.

Adolescent↗
PubMed2002

[Interventions for improvement of primary care in patients with low back pain: how effective are advice to primary care physicians on therapies and a multimodal therapy program arising out of cooperation of outpatient health care structures?].

BACKGROUND: Treatment for chronic low back pain in primary care has a poor-quality outcome. There is evidence that multimodal therapy is the most successful approach to its management. We tried to evaluate whether giving primary care physicians evidence-based recommendations on therapy of chronic back pain or directly implementing a multimodal program would improve the outcome of patients with low back pain treated in primary care. METHODS: In the first phase, physicians were asked to document the course of patients suffering from low back pain of at least 4 weeks' duration with no decrease in intensity, noting pain intensity before and after 6 months of conventional, nonsurgical treatments. In the present, second, phase of the study, recommendations issued by the Medicines Committee of the German Medical Profession and the U.S. Agency for Health Care Policy and Research for the management of back pain were presented to doctors in printed form and at conferences. In parallel with this, a multimodal program for the treatment of chronic low back pain (4 h/day for 20 days: medical training therapy, cognitive-behavioral therapy, physiotherapy, and patient education) was organized in a private health-oriented sports center in cooperation with three private physiotherapy practices, and a psychologist and a pain specialist from the outpatient pain clinic at the University Hospital in Erlangen. We examined how physicians changed the therapy and how effective it was, the latter as reflected in the mean sum value of the percent pre- to posttreatment changes in pain intensity, how much pain interfered with daily living, depressivity, and quality of life. Data after interventions were compared with baseline data from the first phase. RESULTS: Data relating to 36 patients following treatment by 14 primary care physicians who had been given information about therapy recommendations and to 51 patients who had participated in the multimodal therapy program were compared with baseline data recorded in 157 patients. Recommendations changed neither the therapy preferred by primary care physicians nor the quality of outcome of conventional treatment. In contrast, the multimodal program of therapy for chronic low back pain improved the outcome significantly more than conventional therapy (mean improvement in general outcome score 22 vs. 7%, respectively, compared with baseline data; P<0.001). CONCLUSIONS: Giving primary care physicians information on the therapy recommended for treatment of low back pain does not lead to any change in physicians' preferred therapy. Multimodal programs for treatment of chronic low back pain should be organized locally, with existing health care providers joining forces to improve the quality of outcome in chronic low back pain managed in primary care.

Adult↗
PubMed2000

Reversed-phase liquid chromatography of proteins and peptides using multimodal copolymer-encapsulated silica.

Multimodal copolymer-encapsulated particles for liquid chromatography were prepared by bonding 1-octadecene and unsaturated carboxylic acids on silica particles (5 microm diameter, 300 A pores) for liquid chromatography of proteins. These multimodal copolymer-encapsulated particles can provide both hydrophobic and hydrogen bonding interactions with polar compounds. The chromatographic performance of these multimodal copolymer-encapsulated particles for peptide and protein separations was evaluated under reversed-phase conditions. Compared with typical C8-bonded silica, polymer-encapsulated particles were more stable in acidic mobile phases and provided better recoveries, especially for large proteins (Mr>0.5 x 10(6)). Totally hydrophobic polymer-encapsulated particles were found to produce broad peaks for proteins, and significant improvements were observed by introducing hydrophilic groups (-COOH) onto the polymer-encapsulated surface to form a multimodal phase. For the reversed-phase liquid chromatography of peptides and proteins, improved selectivity and increased solute retention were found using the multimodal polymer-encapsulated particles. More peaks were resolved for the separation of complex peptide mixtures such as protein digests using the multimodal polymer-encapsulated particles as compared to totally hydrophobic polymer-encapsulated particles.

Chromatography, High Pressure Liquid↗
PubMed2006

Multimodality intraoperative neurophysiologic monitoring findings during surgery for adult tethered cord syndrome: analysis of a series of 44 patients with long-term follow-up.

STUDY DESIGN: Prospective analysis of a consecutive series in which multimodality intraoperative neurophysiologic monitoring was used as an adjunct to microneurosurgery for adult tethered cord syndrome. The results of multimodality intraoperative neurophysiologic monitoring were compared with the "gold standard" (neurologic outcomes). OBJECTIVE: To assess the sensitivity, specificity, and positive and negative predictive values of multimodality intraoperative neurophysiologic monitoring in surgery for adult tethered cord syndrome. SUMMARY OF BACKGROUND DATA: Although intraoperative electrophysiologic techniques may help to minimize neural injury during spinal microneurosurgery, to our knowledge, no study has quantitatively evaluated the value of multimodality intraoperative neurophysiologic monitoring in the management of adult tethered cord syndrome. METHODS: Multimodality intraoperative neurophysiologic monitoring included posterior tibial nerve somatosensory evoked potentials (SSEPs), continuous electromyographic (EMG) monitoring of the L2 to S4 myotomes, and evoked EMG. Follow-up neurologic evaluations were performed for at least 1 year. RESULTS: A total of 44 consecutive patients, including 19 males and 25 females (aged 43 +/- 15 years), who underwent microsurgery for adult tethered cord syndrome were evaluated. After surgery, new neurologic deficits, including 1 transient and 1 permanent, developed in 2 patients. There was 1 patient who had persistent posterior tibial nerve SSEP amplitude reduction following microsurgical manipulation. In 1 patient, a transient posterior tibial nerve SSEP amplitude reduction prompted a change in microneurosurgical strategy. This patient awoke with no new postoperative neurologic deficits. For SSEPs, the sensitivity was 50% and specificity 100%. EMG bursts were recorded in 36 patients (82%). The 2 patients with postoperative neurologic worsening had EMG activity in the myotomes, where their new deficits presented. Continuous EMG had a sensitivity of 100% and a specificity of 19%. CONCLUSIONS: To our knowledge, this is the largest series to date reporting the use of multimodality intraoperative neurophysiologic monitoring in the surgical management of adult tethered cord syndrome. Posterior tibial nerve SSEPs have high specificity, but low sensitivity, for predicting new neurologic deficits. In contrast, continuous EMG showed high sensitivity and low specificity. Evoked EMG accurately identified functional neural tissue. The combined recording of SSEPs in concert with continuous and evoked EMGs may provide a useful adjunct to complex microsurgery for adult tethered cord syndrome.

Adult↗
PubMed2006

Multimodal pain stimulation of the gastrointestinal tract.

Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation (e.g., electrical, mechanical, thermal and chemical stimulation) of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients. Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract. Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.

Abdominal Pain↗
PubMedDate not supplied

Multimodal approach and its impact on survival for patients with hepatocellular carcinoma.

BACKGROUND: There are few studies evaluating the prognostic impact on survival of treatment strategy in patients with hepatocellular carcinoma (HCC). The aim of this study was to analyse whether a multimodal approach, that represents a synergic association of different therapeutic procedures, may improve survival of patients with HCC. PATIENTS AND METHODS: Two hundred and fourteen patients with HCC were enrolled in the study. The multimodal approach was chosen for 27 out of 106 (25%) non surgical patients, 42 out of 81 (52%) patients who underwent liver resection and 19 out of 27 (70%) patients who underwent liver transplantation. RESULTS: The long-term survival of patients who underwent the multimodal approach improved significantly with respect to patients treated by both resection and other therapies alone. The 5-year survival rates were 52% vs. 11% (p < 0.05) in the non surgical group and 40% vs. 24% (p < 0.05) in the resection group when a multimodal approach was used for the treatment of recurrences. In patients with advanced HCC undergoing liver transplantation, multimodal treatment resulted in long-term survival comparable to that of patients with early HCC. CONCLUSION: A multimodal approach should be suggested in all patients with HCC, since a careful integration of surgical and non surgical treatments may improve long-term survival in such patients.

Adolescent↗