Short-term Therapeutic Response Research Articles

Electroclinical Landscape of Infantile Epileptic Spasms Syndrome.

To elucidate the electroclinical characteristics of infantile epileptic spasms syndrome (IESS) and to determine any potential association among these with underlying etiologies and response to therapy. Sixty-eight, treatment-naive children with IESS underwent long-term video electroencephalogram (EEG) recording, which was used to characterize the semiology, ictal, and inter-ictal EEG patterns. Children were further followed up to assess electroclinical predictors of etiologies and short-term therapeutic response. Of 68 children enrolled (69% boys), the median age at enrollment was 10.5 mo (IQR-8). Eighty-eight percent of children had flexor spasms, followed by mixed (7%) and extensor (4.4%). Asymmetrical spasms were noted in 17.6% children, and all of them had underlying structural etiology. Two children had the status of epileptic spasms. In the present cohort, authors recognized five distinct ictal EEG correlates of epileptic spasms; the frontocentral dominant slow wave was the most prevalent (32%), followed by the generalized slow-wave complex with superimposed fast rhythm in 29.4%. The occipital dominant slow wave complex was a peculiar pattern in 16%. The major underlying etiologies were hypoxic-ischemic brain injuries (36.7%) and neonatal hypoglycemic brain injuries (22%). Besides asymmetric spasms, authors could not identify any significant association among electroclinical characteristics, underlying etiologies and response to therapy in this study. The electroclinical landscape of IESS is peculiar and diverse in developing countries. The presence of asymmetrical spasms indicated underlying structural etiology.

Magnitude, determinants, and impact of treatment lag in West syndrome: A prospective observational study

Abstract Aim: Early recognition and initiation of standard therapy are crucial for the management of West syndrome. The study aimed to assess the magnitude, potential determinants, and impact of treatment lag impact on short-term therapeutic outcomes. Materials and Methods: The study design was prospective, observational, and data were ascertained through personal interviews with caregivers and reviewing medical records according to a pre-structured questionnaire. We defined short-term therapeutic response as the cessation of epileptic spasms commencing within 14 days of initiation of hormonal therapy and sustained for ≥28 days. Results: Of 82 consecutively enrolled children with West syndrome, the median treatment lag was 90 days (95% confidence interval [CI]: 110–198 days). The significant determinants of treatment lag in our study were as follows: the preexisting developmental delay, educational status of the parents, and qualification of the first practitioner visited. Our study showed that a shorter treatment lag (<1 month) was associated with a favorable cessation of epileptic spasms (85% vs. 15%; P = 0.011). Conclusion: We observed a significant treatment lag in children with West syndrome. The lead time to treatment emerged as a potentially modifiable risk factor for short-term therapeutic response with hormonal therapy.

Electroencephalographic Network Topologies Predict Antidepressant Responses in Patients With Major Depressive Disorder.

Medication therapy seems to be an effective treatment for major depressive disorder (MDD). However, although the efficacies of various medicines are equal or similar on average, they vary widely among individuals. Therefore, an understanding of methods for the timely evaluation of short-term therapeutic response and prediction of symptom improvement after a specific course of medication at the individual level at the initial stage of treatment is very important. In our present study, we sought to identify a neurobiological signature of the response to short-term antidepressant treatment. Related brain network analysis was applied in resting-state electroencephalogram (EEG) datasets from patients with MDD. The corresponding EEG networks were constructed accordingly and then quantitatively measured to predict the efficacy after eight weeks of medication, as well as to distinguish the therapeutic responders from non-responders. The results of our present study revealed that the corresponding resting-state EEG networks became significantly weaker after one week of treatment, and the eventual medication efficacy was reliably predicted using the changes in those network properties within the one-week medication regimen. Moreover, the corresponding resting-state networks at baseline were also proven to precisely distinguish those responders from other individuals with an accuracy of 96.67% when using the spatial network topologies as the discriminative features. These findings consistently provide a deeper neurobiological understanding of antidepressant treatment and a reliable and quantitative approach for personalized treatment of MDD.

Clinical characteristics and prognosis of anti-alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic acid receptor encephalitis

BackgroundEncephalitis associated with antibodies against alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is an extremely rare type of antibody-mediated encephalitis. This research aims to investigate the clinical characteristics and prognosis of anti-AMPAR encephalitis.MethodsThis retrospective study enrolled nine patients with anti-AMPAR encephalitis. Demographic information, clinical manifestations, laboratory and radiological findings, treatment and response were collected and analyzed. These patients were followed up with an average period of 72 weeks to gather prognostic information.ResultsNine patients (7 females and 2 males) were enrolled with a mean age at disease onset of 59 years old. Three clinical pictures, including limbic encephalitis (n = 7; 78%), pure amnesia (n = 1; 11%) and fulminant encephalitis (n = 1; 11%) were identified. New symptoms of dysphagia and deafness were identified in the clinical spectrum of anti-AMPAR encephalitis. All patients had positive blood AMPAR antibodies, and six of them (67%) had paired positive antibodies in cerebrospinal fluid (CSF). Brain magnetic resonance imaging (MRI) was abnormal in 75% of the patients with no specific patterns recognized. Six patients (67%) had tumors, including lung cancers and thymomas. After immunotherapy and oncotherapy, partial improvement of neurological symptoms was observed among all 6 patients with available records during their hospitalization. After a mean follow-up of 72 weeks, 3 patients had marked decrease of modified Rankin Scale (mRS) score, 1 patient had unchanged mRS score, 4 patients died and the other one was lost.ConclusionsAnti-AMPAR encephalitis mainly presents as limbic encephalitis, and is paraneoplastic in 67% of cases. Thus, intensive screening for tumors is recommended for all anti-AMPAR patients. Although patients showed a good short-term therapeutic response, the overall prognosis was not satisfactory.

Plasma Calcitonin Gene-Related Peptide: A Potential Biomarker for Diagnosis and Therapeutic Responses in Pediatric Migraine.

Background: Plasma calcitonin gene-related peptide (CGRP) plays a key role in the migraine pathophysiology. This study aimed to investigate its role in predicting diagnosis and outcome of pharmacotherapy in pediatric migraine.Methods: We prospectively recruited 120 subjects, who never took migraine-preventive agents in a pediatric clinic, including 68 patients with migraine, 30 with non-migraine headache (NM), and 22 non-headache (NH) age-matched controls. Short-term therapeutic response was measured for at least 2 weeks after the start of therapy. Responders were defined with >50% headache reduction. Plasma CGRP concentrations were measured by ELISA.Results: In the migraine group, more patients required acute therapy, as compared to the NM group (62/68, 91% vs. 5/30, 15%, p = 0.001). The mean plasma CGRP level in migraineurs either during (291 ± 60 pg/ml) or between (240 ± 48) attacks was higher than in NM patients (51 ± 5 pg/ml, p = 0.006 and 0.018, respectively) and NH controls (53 ± 6 pg/ml, p = 0.016 and 0.045, respectively). Forty-seven patients (69%) needed preventive treatments and had higher plasma CGRP levels (364 ± 62 pg/ml, n = 47) than those not (183 ± 54 pg/ml, n = 21) (p = 0.031). Topiramate responders had higher plasma CGRP levels than non-responders (437 ± 131 pg/ml, n = 14 vs. 67 ± 19 pg/ml, n = 6, p = 0.021). Survival curves of plasma CGRP levels also showed those with higher CGRP levels responded better to topiramate. Differences were not found in the other preventives.Conclusion: The plasma CGRP level can differentiate migraine from non-migraine headache. It may also serve as a reference for the therapeutic strategy since it is higher in patients requiring migraine prevention and responsive to short-term topiramate treatment. These results are clinically significant, especially for the young children who cannot clearly describe their headache symptoms and may provide new insights into the clinical practice for the diagnosis and treatment of pediatric migraine.

Utility of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as biomarker to predict therapeutic response to methotrexate in rheumatoid arthritis.

The objective of this study was to investigate the usefulness of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in predicting short-term therapeutic response to methotrexate (MTX) in rheumatoid arthritis (RA). Patients with active RA, with Disease Activity Score-28 joints (DAS-28) >3.2, starting oral MTX, were included. We measured at baseline, 3 and 6 mo: DAS-28, Health Assessment Questionnaire-Disability Index (HAQ-DI), patient's perception of disease severity, morning stiffness and pain, as well as modifications in sTREM-1 levels. A reduction in DAS-28 > 1.2 at 3 or 6 mo was considered adequate response. A significant decrease in DAS-28 was observed at 3 and 6 mo. HAQ-DI also decreased at 3 and 6 mo. No significant changes were observed in sTREM-1 levels at 3 or 6 mo. Using as cut-off a baseline value of sTREM-1 levels > 390 pg/ml, we obtained low values of sensitivity (61.5%), specificity (59.3%), positive predictive value (59.3%) and negative predictive value (61.5%) for adequate response to MTX at 3 mo. We found no clinical value of sTREM-1 levels in predicting therapeutic response to MTX in RA. Further studies should evaluate if sTREM-1 levels are predictive for other outcomes, including higher structural damage or good response to biologics.

Clinical Significance of Antinuclear and Antiextractable Nuclear Antigen Antibody in Childhood Immune Thrombocytopenia.

This study aims to determine the clinical significance of positive antinuclear/antiextractable nuclear antigen (ANA/A-ENA) antibody on manifestation and therapeutic response of childhood immune thrombocytopenia (ITP). Overall, 1,330 patients aged between 1 and 15.6 years diagnosed with primary ITP were retrospectively analyzed, excluding those with secondary ITP. Bleeding manifestations were recorded. All patients underwent autoantibody testing and follow-up for 32 months on average (range: 23-54 months). Steroid response was also assessed. Response rates were compared between ANA/A-ENA-positive and ANA/A-ENA-negative patients. Of all the patients enrolled, 84 tested positive only for ANA, 102 tested positive for A-ENA, 54 tested positive for both ANA and A-ENA, and 1,090 tested negative for both. Patients who were ANA/A-ENA positive were more likely to be female and older than 10 years. Patients who were A-ENA positive were more likely to have either persistent or chronic disease and suffer from life-threatening bleeding as well as poor short-term therapeutic response. We conclude that autoantibody testing is important to determine the short-term prognosis of ITP patients. Females, patients older than 10 years of age, and patients with either mixed positivity or A-ENA positivity should be more closely monitored.

Early Response of Hepatocellular Carcinoma to Chemoembolization: Volume Computed Tomography Liver Perfusion Imaging as a Short-Term Response Predictor.

The aim of this study was to investigate the efficacy of lesion-oriented whole-liver computed tomography (CT) perfusion for predicting transarterial chemoembolization early treatment response in patients with hepatocellular carcinoma (HCC). Volume helical shuttle CT perfusion imaging on the whole liver was prospectively performed on 39 patients with 46 independent HCC lesions before target-selected chemoembolization. The therapeutic effects were assessed: responder group included lesions with a complete and partial response, whereas the nonresponder group contained stable and progressive disease. The perfusion parameter value comparison between 2 groups and receiver operating characteristic analyses were performed. The responders demonstrated higher hepatic arterial perfusion (HAP) and hepatic arterial perfusion index (HAPI) and lower hepatic portal perfusion (HPP) compared with the nonresponders among the 34 lesions without Vp3 or Vp4 portal vein thrombosis. In addition, HAP and HAPI had good prognostic values. Whole-liver CT perfusion allows for hemodynamic evaluation of HCC lesions. The HAP, HAPI, and hepatic portal perfusion values may be useful predictors of short-term therapeutic response after transarterial chemoembolization.

4:03 PMAbstract No. 135 - Does tumor size correlate with biochemistry marker when evaluating the short-term therapeutic response of liver metastatic neuroendocrine tumor to yttrium-90 radioembolization?

4:03 PMAbstract No. 135 - Does tumor size correlate with biochemistry marker when evaluating the short-term therapeutic response of liver metastatic neuroendocrine tumor to yttrium-90 radioembolization?

Retrospective Analysis of Survival Improvement by Molecular Biomarker-Based Personalized Chemotherapy for Recurrent Ovarian Cancer

Aggressive tumors such as epithelial ovarian cancer (EOC) are highly heterogeneous in their therapeutic response, making it difficult to improve overall response by using drugs in unselected patients. The goal of this study was to retrospectively, but independently, examine whether biomarker-based personalized chemotherapy selection could improve survival of EOC patients. Using in vitro drug sensitivity and patient clinical outcome data, we have developed co-expression extrapolation (COXEN) biomarker models for predicting patient response to three standard chemotherapy drugs used to treat advanced EOC: paclitaxel, cyclophosphamide, and topotecan, for which sufficient patient data were available for our modeling and independent validation. Four different cohorts of 783 EOC patients were used in our study, including two cohorts of 499 patients for independent validation. The COXEN predictors for the three drugs independently showed high prediction both for patient short-term therapeutic response and long-term survival for recurrent EOC. We then examined the potential clinical benefit of the simultaneous use of the three drug predictors for a large diverse EOC cohort in a prospective manner, finding that the median overall survival was 21 months longer for recurrent EOC patients who were treated with the predicted most effective chemotherapies. Survival improvement was greater for platinum-sensitive patients if they were treated with the predicted most beneficial drugs. Following the FDA guidelines for diagnostic prediction analysis, our study has retrospectively, yet independently, showed a potential for biomarker-based personalized chemotherapy selection to significantly improve survival of patients in the heterogeneous EOC population when using standard chemotherapies.

Clinical features and prognostic factors in patients with leptomeningeal metastases

To investigate the clinical characteristics and prognostic factors of leptomeningeal metastases (LM) from solid tumors and to develop better treatment strategies. The clinical characteristics and follow-up results of 77 cases of leptomeningeal metastases (LM) from solid tumors diagnosed and treated in our hospital from 2002 to 2011 were retrospectively analyzed. Clinical characteristics, treatment methods and overall survival were analyzed using Kaplan-Meier method and Cox regression model. The median survival time for all the patients was 88 days. KPS score, control of the primary tumor and systemic treatment were correlated with survival time for the patients (P < 0.05 for all). The median survival time of systemic treatment was 150 d and those without systemic treatment (chemotherapy and/or targeted therapy) after LM was 60 d (P = 0.001). Systemic therapy combined with local treatment (radiotherapy to the meninges or intrathecal chemotherapy) further improved the survival time of patients. Multivariate analysis showed that KPS and short-term therapeutic response for the LM were independent prognostic factors (P < 0.05 for both). KPS and short-term therapeutic response are independent prognostic factores for leptomeningeal metastases from solid tumors. Systemic chemotherapy or targeted therapy can prolong the survival time. Systemic treatment (chemotherapy and/or targeted therapy) combined with radiation therapy or intrathecal injection may further improve the clinical outcomes.

Técnicas de imagen en infección musculoesquelética

Imaging techniques are routinely used to evaluate patients with suspected musculoskeletal infection. Although radiographs will not establish the diagnosis, they should always be performed when infection is suspected because of their utility in differential diagnosis and follow-up. Radiographs provide an overview of the anatomical region of interest and of previous alterations that can influence the selection and interpretation of subsequently used techniques. Magnetic resonance imaging is the most sensitive examination, does not irradiate, and provides excellent anatomic detail and rapid results. This technique is especially valuable in spondylodiscitis, osteomyelitis, and diabetic foot infections. Its main limitations are the false-positives caused by nonspecific bone edema and poor reliability in the assessment of short-term therapeutic response. Among nuclear medicine procedures, the 3-phase bone scan is widely available and highly accurate in previously healthy bone. Labeled leukocyte scintigraphy should be used in complicated osteomyelitis, such as prosthetic infection, although it is also useful to exclude infection in diabetic foot and neuropathic joints. Ga-67 scintigraphy is useful in spinal infections. In these infections, positron emission tomography can also be a useful alternative. Finally, it is important to remember atypical radiological presentations in distinct locations and particular clinical situations, as well as certain conditions that can mimic infection.

Radiotherapy for and prognosis of breast cancer patients with local-regional recurrence after mastectomy

Controversies remain regarding the therapeutic principle for and prognosis of breast cancer patients with isolated local-regional recurrence after mastectomy. This study was to evaluate the role of radiotherapy in treating these patients and to investigate the prognosis. Clinical data of 255 breast cancer patients with chest-wall and/or regional lymph node recurrence as first failure after mastectomy from 1990 to 2005 were analyzed. All patients received radiotherapy for recurrence. The median follow-up time was 45 months (9 months-15.5 years). The median disease-free interval (DFI) was 22 months (2-260 months); it was 37 months in patients with positive hormonal receptor and 17 months in those with unknown or negative receptor. The 2-, 5-, and 8-year overall survival (OS) rates were 86.4%, 56.5%, and 35.0%, respectively. The median survival time was 79 months. The 2-, 5-and, 8-year local control rates were 6.1%, 36.3%, and 27.6%, respectively. Univariate prognostic analysis showed that DFI, site and number of recurrence, receptor status, short-term therapeutic response, initial T status and axillary involvement significantly affected the survival (all P<0.05); multivariate analysis showed that DFI, receptor status, site and number of recurrence were independent prognostic factors. Prognostic index was established to classify the patients. The 2-, 5-and 8-year OS rates were 100%, 91.6%, and 56.4% in the favorable prognosis group, 88.1%, 59.1%, and 36.8% in the medium prognosis group, 68.0%, 8.5%, and 0 in the poor prognosis group (P<0.001). Radiotherapy is effective for breast cancer patients with isolated local-regional recurrence after mastectomy. Prognostic index could be applied to predict the prognosis.

Treatment Response of Modified Tinnitus Retraining Therapy with Medical Therapy in the Patients with Tinnitus

Background and ObjectivesZZAccording to the neurophysiologic model of tinnitus, emotion and autonomic nervous systems are closely related to generation of tinnitus. We performed this study to evaluate the treatment response of modified tinnitus retraining therapy (TRT) with medication in the patients with sensorineural tinnitus. Subjects and MethodZZForty-three tinnitus patients who were diagnosed as sensorineural tinnitus through audiologic evaluation and have normal hearing in speech frequency were included in this study. Tinnitus and psychological status were measured by tinnitus questionnaire, Korean version of Brief Encounter Psychosocial Instrument (BEPSI) scale, Beck Depression Inventory (BDI), Spielberger State Trait Anxiety Inventory (STAI). Patients treated with anxiolytics and microcirculation enhancer were Group 1 and those treated with modified TRT and medications were Group 2. Short-term therapeutic response was analyzed and compared between two groups. ResultsZZLoudness, awareness, annoyance and effect on life of tinnitus and tinnitus handicap score were significantly decreased in Group 2. Relief of tinnitus in more than 2 of 4 subjective parameters was achieved in 4 patients (30.7%) in Group 1 and 15 patients (75%) in Group 2. Stress score was also decreased significantly after treatment in Group 2. ConclusionZZTinnitus patients in Group 2 treated with medication and modified TRT showed the higher compliance and the response rate of treatment than the patients in Group 1 treated with medication alone. Modified TRT, in addition to medical therapy, should be considered to increase the therapeutic response in patients with sensorineural tinnitus. Korean J Otorhinolaryngol-Head Neck Surg 2009;52:648-54 Key WordsZZTinnitus·Stress·Depression·Anxiety·Tinnitus retraining therapy.

Contrast-enhanced ultrasound in assessment of the therapeutic efficacy of high intensity focused ultrasound in treating hepatocellular carcinoma

AIM:To evaluate the role of contrast-enhanced ultrasonography in assessing the short-term therapeutic response of hepatocellular carcinoma with high intensity focused ultrasound(HIFU).METHODS:Thirty two patients with hepato-cellular carcinoma(HCC)received HIFU treat-ments including 23 part-covered treatments and 9 full-covered treatments.Contrast-enhanced ultrasound(CEUS)imaging was performed to monitor the response of tumor vessels to HIFU ablation before the treatment and 1-4d after the treatment separately.Simultaneously,all patients underwent routine US for comparison.RESULTS:Compared with tumor images in the patients before HIFU which showed multiple blood flow signals,clinical images showed an abrupt interruption,followed by the cessation of blood flow within the tumor vessels after HIFU treatment,demonstrating that homogeneous coagulative necrosis occurred in the treatment area.According to the final diagnosis as gold standard,the accuracy of CEUS for HIFU was much better than the conventional ultrasonogra-phy(90.6% vs 46.9%,P0.05).CONCLUSION:CEUS can accurately differentiate tumor necrosis and evaluate therapeutic efficacy of HIFU.

Asthma and cigarette smoking

In most developed countries approximately 25% of adults with asthma are current cigarette smokers. Asthma and active cigarette smoking interact to cause more severe symptoms, accelerated decline in lung function, and impaired short-term therapeutic response to corticosteroids. Cigarette smoking may modify inflammation that is associated with asthma, although there is limited published data on airway pathology in smokers with asthma. To date, the evidence points towards a combination of both heightened and suppressed inflammatory responses in smokers compared with nonsmokers with asthma. The mechanisms of corticosteroid resistance in asthmatic smokers are unexplained, but could be as a result of alterations in airway inflammatory cell phenotypes (e.g. increased neutrophils or reduced eosinophils), changes in the glucocorticoid receptor-alpha to -beta ratio (e.g. overexpression of glucocorticoid receptor beta), and increased activation of pro-inflammatory transcription factors (e.g. nuclear factor-kappaB) or reduced histone deacetylase activity. In conclusion, every effort should be made to encourage asthmatics who smoke to stop, although the effects of smoking cessation upon reversing the adverse effects of tobacco smoke on asthma control, therapeutic response to corticosteroids and airway pathology have yet to be fully elucidated. Alternative or additional therapies to inhaled corticosteroids are needed for asthmatic patients who are unable to quit smoking.