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PubMed2003

Multimodality targeted approach in redo off-pump coronary artery bypass surgery.

Records of 86 patients who underwent off-pump redo coronary revascularization between December 1997 and December 2000, were analyzed. Approaches included median sternotomy (47), anterolateral thoracotomy for left anterior descending artery and diagonal targets (35), posterolateral thoracotomy for the obtuse marginal with proximal anastomosis on descending aorta (3), and a combined subxiphoid-anterior thoracotomy approach (1) for right gastroepiploic artery-to-left anterior descending artery anastomosis. The mean age was 61.82 years. There were 2 (2.3%) operative deaths. Complications included perioperative myocardial infarction in 4 patients and reexploration for bleeding in one. Blood transfusion was required in 12 patients. The mean length of hospital stay was 5 +/- 2 days. A multimodality targeted approach for off-pump redo coronary artery bypass offers a less invasive but safer method of myocardial revascularization, with decreased complications, lower blood product requirement, and early hospital discharge.

Aged↗

PubMedDate not supplied

Extrapulmonary small cell carcinoma: multimodality treatment results.

AIMS AND BACKGROUND: Extrapulmonary small cell carcinoma is a distinct entity that can occur in many sites, and it is pathologically similar to small-cell lung cancer. We report the results of a retrospective study of a multimodality treatment of 16 consecutive patients with a diagnosis of extrapulmonary small-cell carcinoma. METHODS: Primary tumor site was prostate in 2, gallbladder in 2, uterine cervix in 2, liver in 2, endometrium in 1, epididymis in 1, colon in 1, larynx in 1, breast in 1, and unknown primary tumor in 3 patients. Patients' ages ranged from 19 to 79 years (median, 62). Nine patients had limited and 7 had extensive disease. Histologically, 14 were pure extrapulmonary small-cell carcinoma and 2 were mixed with squamous-cell carcinoma. RESULTS: Curative surgery was attempted in 8 patients. Seven patients received local-regional adjuvant radiotherapy. All patients, except the one with a breast primary, were treated with chemotherapy (mostly platinum-based regimens). Overall survival for all patients was 41% and 11% at 2 and 5 years, respectively (median survival, 14 months). Median survival for patients with limited disease was 25 months compared to 12 months for patients with extensive disease (P = 0.05). CONCLUSIONS: Treatment results for extrapulmonary small-cell carcinoma are comparable to those of small-cell carcinomas of the lung. Extent of disease is a significant prognostic factor for survival.

Adult↗

PubMedDate not supplied

The evolving role of radiation therapy in the optimal multimodality treatment of childhood cancer.

Childhood cancer is rare, representing only 1% of the total cancer problem. Of children diagnosed with cancer today, more than 70% are predicted to be long-term survivors. Essentially all pediatric cancers are treated by interdigitating radiation with surgical resection and systemic chemotherapy. The use of irradiation, important to achieve high rates of disease local control, must be always balanced against late effects specifically related to this treatment modality, principally growth retardation and second tumors induction. Using neuroblastoma, Wilms' tumor and rhabdomyosarcoma as examples, the advances in the optimal multimodality treatment of childhood cancer and the evolution of the role of radiation therapy are discussed.

Child↗

PubMed1994

Predicting outcome in a multimodal day treatment program for children with severe behaviour problems.

The demand for day treatment programs for children with severe behaviour problems has greatly increased in the past decade. The objective of this study is to identify characteristics of children who benefit most from such a program. The sample consisted of 63 children, aged five to 13, assessed at admission and discharge from the program. Outcome measures included behavioural improvement and school reintegration. At admission, multivariate analyses revealed that children who made the greatest behavioural improvements had less severe behaviour problems, lower IQ scores and more disturbed family functioning. Children reintegrated into regular classes after discharge were younger at admission, had better reading skills, no attention deficit hyperactivity disorder and little parental marital discord. Findings suggest that successful outcome can be predicted from characteristics of children at intake. A multimodal approach is needed to address the different problems areas in a child's life.

Adolescent↗

PubMed1999

Fact versus fancy concerning the multimodal treatment study for attention-deficit hyperactivity disorder.

Findings from the Multimodal Treatment Study of Children With Attention-Deficit Hyperactivity Disorder (ADHD), the MTA, have been much discussed but frequently misinterpreted or mischaracterized. Misinterpretations regarding the specific nature of and rationale for the study design, the effectiveness of the behavioural treatment arm, the possible advantages of combined treatments over single-component (medication management or behavioural therapy) interventions, and the feasibility and applicability of MTA treatments for "real-world" practitioners are addressed. Careful interpretation of the MTA findings suggests that for ADHD symptoms, carefully crafted medication-management approaches are superior to behavioural treatment and to routine community care that includes medication. For non-ADHD areas of functioning (for example, social skills, academic performance), combined treatments may offer modest advantages over single-component approaches. Longer-term outcomes past 14 months of intensive MTA treatments (as well as their relative effectiveness with respect to each other) remain unknown, pending further MTA analyses. The MTA treatments by and large consisted of evidence-based "best practices." Thus, rather than characterizing these treatments as infeasible, the substantially superior outcomes of these treatments (versus routine clinical care) across diverse settings should help set the standard for future treatment practices in real-world settings. Despite important study limitations, the MTA study, by virtue of its size, scope, and length; parallel-groups design; explicit use of manualized, evidence-based treatments; and comprehensive range of outcome assessments sets an important benchmark for future trials testing new treatments for childhood ADHD and defines a new standard for optimal outcomes that can be achieved with the best of clinical care.

Attention Deficit Disorder with Hyperactivity↗

PubMed1999

The NIMH multimodal treatment study for attention-deficit hyperactivity disorder: just say yes to drugs alone?

The outcome, merits, and limitations of the Multimodal Treatment Study for Children With Attention-Deficit Hyperactivity Disorder (ADHD), the MTA study, are described and discussed. Consideration is given to design issues that make the MTA a landmark study for clinicians and researchers working with ADHD children. These include the large, heterogeneous sample, the state-of-the-art treatment, the lengthy treatment period, the extensive documentation of treatment manuals, and the attention paid to treatment fidelity and adherence. Also highlighted are facets of the design that predisposed the study in favour of a differentially positive outcome for pharmacological relative to behavioural treatment. Primary among these is the fact that outcome was measured 4-6 months after the intensive phase of behaviour treatment and after therapeutic contact with the behaviour therapist had ended but while medication treatment was active and in its most intensive phase. Finally, the outcome for the combined treatment condition in the MTA is discussed in the context of the extant literature and directions for future research.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Study of multimodal evoked potentials in patients with type 1 Gaucher's disease.

To detect early subclinical nervous dysfunction in Gaucher's disease type 1, we carried out motor, brainstem auditory, visual, and somatosensory evoked potentials in 17 patients with Gaucher's disease type 1. Central motor evoked potential abnormalities were found in nine patients (69.2%), consisting of an increased motor threshold in all, with prolonged central motor conduction time in two patients. Brainstem auditory evoked potentials were abnormal in five patients (31.2%), and the most frequent abnormality was a bilateral increased I-III interpeak latency. Visual evoked potentials showed a delayed latency of the P100 wave in four patients (25%). Somatosensory evoked potential abnormalities were found in three patients (18.7%), consisting of an increased N13-N20 interval in two patients and a not reproducible N13 wave in one patient. Our findings suggest that the multimodal evoked potential approach provides information about nervous subclinical damage in Gaucher's disease type 1; transcranial magnetic stimulation proved to be the most sensitive tool. Early detection of subclinical neurologic dysfunction can be useful in view of more effective therapeutic strategies.

Adolescent↗

PubMed1996

Multimodal evoked potentials in Alzheimer's disease and Binswanger's disease.

Somatosensory evoked potentials (SEPs), brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs), and auditory event-related potentials (ERPs) were studied in 15 patients with Alzheimer's disease (AD), eight patients with Binswanger's disease (BD), and 15 normal subjects. Patients with BD showed significant prolongation of the interpeak latency between N13 and N20 (N13-N20) and N20-P40 of SEPs as compared with the normal controls, whereas patients with AD only demonstrated significant prolongation of N20-P40. The interpeak latency between waves I and V of BAEPs in patients with both AD and BD was significantly longer than that of controls. There were no significant differences in P100 latency of VEPs among these three groups. Both groups with dementia showed significant prolongation of N200 and P300 latencies of ERPs compared with normal controls. In addition, patients with AD showed significant prolongation of P200 latency. We conclude that these two dementing diseases have different electrophysiologic features that may be related to their underlying pathogenetic mechanisms. Furthermore, the measurement of multimodal evoked potentials may be helpful in the differential diagnosis of AD and BD.

Aged↗

PubMed2005

Reducing the risk of myocardial revascularization: relevance of multimodal brain monitoring.

Perioperative neurologic events in heart surgery are the most devastating complications. Although myocardial revascularization without cardiopulmonary bypass (CPB) has reduced the incidence of cerebrovascular accidents, they still remain a reality that the cardiothoracic surgeon is unable to completely eliminate. The events leading to a neurologic complication are related to hemodynamic instability and embolization of aortic debris at the time a side-biting clamp is applied. Combined events may eventually impact the brain to varying degrees, ranging from a temporary confusional state to a full-blown stroke from which meaningful recovery may be impossible. This report describes the interventions necessary to maintain hemodynamic stability, the role of brain monitoring required, and how to safely achieve complete off-CPB myocardial revascularization and minimize the incidence of neurologic complications. Cardiac interventions include maintaining sinus rhythm, providing adequate blood supply to all vital organs, and avoiding induction of myocardial ischemia, which may induce supraventricular, ventricular arrhythmias, or both. These interventions depend upon an experienced surgical team (anesthesiologist, cardiologist, surgeon, and operating room and intensive care unit recovery nurses). Anticipation of myocardial ischemia may require loading the patient with antiarrhythmic drugs, and placement of intracoronary shunts and intraaortic balloon pump support. Patience from the surgeon is often required to allow time for the specific intervention to act. In addition to interventions to maintain a balance between the demand and supply of oxygen, we frequently rely on "intermittent hypotensive anesthesia'' while performing the distal and proximal coronary anastomoses. Hypotension may lead to inadequate oxygen supply to the brain, so multimodal brain monitoring becomes mandatory. We use a combination of transcranial brain oximetry and electroencephalographic compressed spectral array. This combined monitoring results in a safer surgical procedure, allowing the hemodynamic interventions to be performed rationally and without interruption of the surgical procedure.

Brain↗

PubMed2005

Organ protection during thoracoabdominal aortic surgery: rationale for a multimodality approach.

Surgical repair of thoracoabdominal aortic aneurysms (TAAAs) remains a technically challenging operation that requires a systematic approach to prevent ischemic complications and achieve excellent clinical outcomes. Techniques for organ protection have evolved substantially over the past 20 years. This review describes our current multimodality approach to organ protection during TAAA repair.

Aortic Aneurysm, Abdominal↗

PubMed2006

A multimodal contrast agent for preoperative MR Imaging and intraoperative tumor margin delineation.

We have constructed a multimodal contrast agent suitable for near-infrared, NIR, fluorescent imaging as well as magnetic resonance imaging, MRI. This class of agents may be useful for preoperative tumor localization and tumor functional evaluation and for intraoperative delineation of tumor margins. We have covalently attached dyes of the cyanine family to a previously described polymeric contrast agent, Gd-DTPA-polylysine, of an extended, uncoiled conformation. The dual modality agent is as effective in imaging tumors by MRI as the parent compound provided that the dye loading on the polymer is such that it does not eliminate all the available free-lysine groups on the parent Gd-DTPA-polylysine polymers. NIR fluorescence from preclinical subcutaneous and orthotopic mammary gland tumors could be detected with a signal to background ratio of as high as 4.5 at 12 hours post agent injection at a dye dose of 125 nmole/kg. For intraoperative delineation of tumor margins, a wide-field illumination camera system was devised giving high signal to background NIR fluorescent images of surgically exposed orthotopic mammary gland tumors. Histologic microscopy confirmed the location of the dual modality agent at the boundary of the tumor with a margin distance of about 0.3 mm from labeled tumor cells.

Animals↗

PubMedDate not supplied

Endoluminal recanalization in a patient with phlegmasia cerulea dolens using a multimodality approach-a case report.

Phlegmasia cerulea dolens is a limb-threatening form of deep venous thrombosis and should be treated aggressively. The authors report a patient who presented with iliocaval and femoral deep venous thrombosis and posed an additional therapeutic challenge based on a recent history of heparin-induced thrombocytopenia. Catheter-directed pharmacologic thrombolysis and balloon venoplasty were applied in treatment. The direct thrombin inhibitor argatroban was used in place of heparin for concurrent anticoagulation. This multimodality endovascular approach (chemical and mechanical interventions) was successful in relieving the venous occlusion and salvaging the limb, while maintaining appropriate treatment for heparin-induced thrombocytopenia.

Anticoagulants↗

PubMedDate not supplied

Multimodal therapy for acute and chronic venous thrombotic and occlusive disease.

Critical deep venous thrombosis and occlusion constitutes a small percentage of patients with venous disease. However, these patients exhibit severe symptomatology including pain and extensive edema that may progress to limb- or life-threatening complications such as phlegmasia cerulea dolens and superior vena cava syndrome. This paper reviews the different multimodal percutaneous interventions currently available for the treatment of complex critical venous thrombotic and occlusive disease.

Acute Disease↗

PubMed2004

Does multimodality therapy of arteriovenous malformations improve patient outcome?

The strategy for treating arteriovenous malformations (AVMs) has undergone changes and long-term follow-up results remain unclear. To compare the outcomes of different treatment strategies, we divided 112 patients with 113 AVMs into groups with hemorrhagic (n = 71, 62.8%) and nonhemorrhagic (n = 42, 37.2%) AVMs and subdivided these according to the period in which they were treated (before/after 1990). In the more recent period, treatment more frequently involved the use of the gamma-knife and microembolization to the AVM as well as combination therapy. Long-term follow-up showed that the complication rate was lower and the Rankin scale better, in the more recently treated group. Based on our findings we suggest that AVMs should be treated aggressively using a multimodality strategy.

Adolescent↗

PubMed2002

Early multimodal therapy in adult Wilms' tumor: case report.

Wilms' tumor occurs rarely in adults, especially after the third decade. In adults, the prognosis of Wilms' tumor is worse than in children. In this case report, we present a 48-year old patient who relapsed with advanced stage shortly after primary surgery. A definitive treatment plan has not been established because of the rarity of this tumor in adults. After surgical removal, multimodal therapy should be begun immediately for long-lasting, complete remission.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2026

Multimodal analysis of CD38 in T-cell Acute Lymphoblastic Leukemia Identifies Combinatorial Therapeutic Strategies.

Outcomes for pediatric patients with refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) are poor, underscoring the need for improved therapeutic strategies. CD38, a type II transmembrane glycoprotein, is a promising target in T-ALL, with clinical trials evaluating CD38-targeting immunotherapies in frontline and relapsed settings. However, the biological role of CD38 in T-ALL has not been systematically defined. We interrogated CD38 biology through multimodal profiling of pediatric T-ALL samples. Bulk RNA sequencing of 1,335 primary tumors revealed that CD38 expression varies across genomic and immunophenotypic subtypes in T-ALL. Flow cytometry of 150 primary samples and CITE-sequencing of 40 cases demonstrated broad surface expression of CD38. A transcription factor CRISPR-screen identified RUNX1, RUNX3, and TP53 as candidate positive regulators of CD38. Metabolomic profiling of cell lines further revealed disruption of the polyamine pathway following CD38 perturbation. Supporting this finding, co-targeting CD38 with difluoromethylornithine (DFMO), a polyamine metabolism disruptor, improved survival in preclinical models. Across transcriptomic datasets, including primary tumors, cell lines, and patient-derived xenograft models, IL32 expression consistently decreased following CD38 loss or negativity, supporting an association between CD38 and inflammatory signaling pathways. Additionally, CD38 and LCK expression were positively correlated across majority of genomic subtypes, implicating SRC kinase signaling. Consistent with this, daratumumab in cell lines increased LCK phosphorylation, and combination therapy with dasatinib improved survival compared to monotherapy. Collectively, these findings define previously unrecognized interactions between CD38 and targetable pathways and genes in T-ALL and identify rational combinatorial strategies to enhance CD38-directed therapies and reduce relapse risk.

Journal Article↗

PubMed2004

Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension.

BACKGROUND: This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals. METHODS: We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 +/- 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound. RESULTS: A new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts. CONCLUSION: In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure.

Blood Flow Velocity↗

PubMed1983

The treatment of writer's cramp with multimodal behaviour therapy and biofeedback: a study of 15 cases.

Of 15 patients with writer's cramp (4 females, 11 males, mean age 36, range 23-50, mean duration 3.6 years), 13 entered a behavioural treatment. Nine received a multimodal treatment, and four EMG feedback alone. Four patients dropped out during the treatment phase. Nine patients were considered as improved at a follow-up between 1 and 9 months. A stress-coping model is put forward to account for the therapeutic effectiveness, and to explain the drop-outs. Writer's cramp seems to be related to stressful situations at work. The existence of personality and biological factors remains to be demonstrated.

Adult↗