scholarly journals M148. NORMALIZATION IN REWARD PROCESSING DURING INITIAL TREATMENT MAY PREDICT LONG-TERM CLINICAL OUTCOME IN ANTIPSYCHOTIC NAïVE SCHIZOPHRENIA PATIENTS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S191-S192
Author(s):  
Mette Nielsen ◽  
Egill Rostrup ◽  
Birte Glenthøj
Keyword(s):  
Symptom Severity ◽  
Repeated Measures ◽  
Initial Treatment ◽  
Reward Processing ◽  
Antipsychotic Treatment ◽  
Repeated Measures Anova ◽  
Fmri Signal ◽  
Long Term Follow Up

Abstract Background Decreased functional magnetic resonance (fMRI) signaling in ventral striatum during reward anticipation has been a consistent finding in unmedicated patients with schizophrenia. Antipsychotic medication may normalize this, which has been associated with improvement in psychotic symptoms. Whether this initial treatment response predict long term clinical outcome have not been examined previously. We here present unique data from a cohort of antipsychotic näive patients, who was examined before and after six weeks of antipsychotic monotherapy, and again after six years of naturalistic treatment. We hypothesized that improved reward related fMRI-signaling in striatum during initial treatment will be associated with less severe symptoms and a higher level of function after six years. Methods Antipsychotic-naïve, first episode patients with schizophrenia and matched healthy controls were examined at three timepoints: Baseline, after six weeks and after six years. During the first six weeks, patients were treated with a D2/3 antagonist, after which they switched to a naturalistic clinical setting. At all three timepoints, fMRI was obtained while participants played a monetary rewarding game. Mean contrast signal during anticipation of salient events was extracted from predefined regions of interest in nucleus accumbens and caudatus. Additionally, symptom severity and level of function were assessed in patients. Remission after six years was defined by the Andreasen criteria. Long term changes in patients were analyzed with paired t-test. Repeated measures ANOVA was used to compare fMRI signal in patients and controls over time. Changes in fMRI signal during the first six weeks was compared between remitted and unremitted patients with students t-test. Correlations between symptom severity, level of function and fMRI signal up were analyzed with Spearman or Pearson as appropriate. Results Long term follow-up data on fMRI and psychopathology was obtained from 25 patients and 28 controls 6.7 (4.3–8.7) years after baseline examinations. In patients, symptomatology and level of function was improved (all p<0.001), and remission criteria was met by 12 (48%) of the patients. Repeated measures ANOVA of the extracted fMRI contrast signal at baseline and six years showed a group*time interaction in left Nucleus accumbens (F=4.8, p= 0.038) and left caudatus (F= 4.08, p=0=049). Mean contrast signal increased in patients but decreased in healthy controls. Change in contrast signal in left caudatus during the first six weeks of treatment differed between remitted and non-remitted patients (t=2.2, p=0.044). An increase in signal during initial treatment was found in patients later being in remission, which was not observed in non-remitted patients. Decreased fMRI contrast signal in left caudatus at six years follow up was associated with a higher level of negative symptoms (r=-0.44, p=0.02) and a lower level of function (r=0.45, p=0.02). Discussion In this long-term follow up study, half of the patients were in remission 4–8 years after their first schizophrenia diagnosis. These individuals were characterized by a normalization of reward anticipation signaling in left striatal regions during their initial treatment with a selective D2/3 antagonist. Schizophrenia is a diagnosis with a heterogeneous outcome, and prognostic biomarkers are still missing. The present results suggest that normalization in reward processing during initial antipsychotic treatment may predict remission six years later. Although these results need to be reproduced, they do support the notion, that patients responding to antipsychotic treatment are characterized by changes in striatal function, which may be predictive for long-term outcome.

scholarly journals LONG-TERM FOLLOW-UP STUDY OF JUVENILE DIFFERENTIATED THYROID CARCINOMA TREATED BY RADIOACTIVE IODINE

2018 ◽  
pp. 87-95
Author(s):  
J. Mihailovic
Keyword(s):  
Prognostic Factors ◽  
Initial Treatment ◽  
Radioactive Iodine ◽  
Recurrent Disease ◽  
Differentiated Thyroid Carcinoma ◽  
Follow Up Study ◽  
Tumor Multifocality ◽  
Long Term Follow Up

The overall prognosis in pediatric differentiated thyroid carcinoma (DTC) is excellent. Recurrent disease is frequent, however, and requires additional treatment. In this study we retrospectively analyzed the outcome of juvenile DTC treated by radioactive iodine (I-131) during the long-term follow-up study of 29 years. Methods: 54 DTC patients (34 females, 20 males; ≤20 years old, mean age, 16,5 years) were treated with 131I (RAI) with a median follow-up of 13 years. Patients (pts) underwent different initial treatment: 49 pts, TTx+RAI; 2 pts, TTx; and 3 pts, STTx. The probability of recurrence and prognostic factors were tested by Kaplan-Meier’s method. Results: Initially, 37/54 pts achieved complete remission (CR), 16/54 pts partial remission (PR), 1/54 had progressive disease (PG). During the follow-up 11 pts (20,4%) who achieved CR developed recurrent disease (RD); median appearance time, 4 years (range, 1–25 years). Probability of recurrence was 15,8% at 5 years; 20,3% at 10 years, 25,6% at 15, 20 and 26 years after initial treatment. Strong predictive factors of recurrence were age (p=0,0001), initial treatment (p=0,0001), and tumor multifocality (p=0,004), while gender, nodal metastases at presentation, distal metastases at presentation, histological type of the tumor, tumor or T stage and clinical stage showed no influence on relapse (p=0,176; p=0,757; p=0,799; and p=0,822, respectively). Patients with RD, PR and PG were retreated, with surgery or surgery plus RAI, receiving cumulative activity up to 40 GBq. The overall outcome in our patients was excellent: 88,9% CR, 5,55% SD, 1,85% PG, 1,85% DRD, and 1,85% OCD. Conclusion: Younger age at diagnosis, less radical primary surgery without subsequent RAI, and tumor multifocality are strong prognostic factors for recurrence. In order to reduce relapse rate and to improve surveillance for recurrent disease, TTx followed by RAI appears to be the most beneficial initial treatment for patients with juvenile DTC. The use of RAI seems to be safe without adverse effects on subsequent fertility and pregnancy or secondary malignancy.

scholarly journals Predictive Factors of Response and Survival of Lenalidomide and Rituximab As Initial Treatment of Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1533-1533 ◽  
Author(s):  
Paolo Strati ◽  
Ralph J. Johnson ◽  
Sheryl G Forbes ◽  
Loretta J. Nastoupil ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Initial Treatment ◽  
Research Funding ◽  
Advisory Board ◽  
Advanced Stage ◽  
Advisory Committees ◽  
Long Term Follow Up ◽  
Baseline Characteristics

Introduction. The combination of rituximab and lenalidomide (R2) is active in patients with untreated indolent lymphoma. Recent randomized trials (RELEVANCE) have demonstrated similar efficacy when compared to standard chemo-immunotherapy backbones. Long term follow up of patients receiving R2 as well as predictors of long term remission and survival have yet to be published. Methods. We prospectively evaluated patients with low grade advanced stage FL who received R2 as initial treatment at our institution between 07/2008 and 10/2014. Lenalidomide was given at 20 mg (day 1-21, in a 28 day cycle) for 6 cycles with rituximab monthly. Lenalidomide starting dose was 10 mg if baseline creatinine clearance was < 60 mL/min. Patients with an objective response continued with 10-20 mg of lenalidomide with rituximab for up to 12 more cycles. Response was evaluated according to 2014 Lugano criteria. Results. One-hundred and one patients were included in the analysis, baseline characteristics are shown in the Table. Median number of provided cycles was 7 (range, 1-20). Median dose of lenalidomide was 20 mg (range, 5-20 mg), and 29 (29%) patients required a dose reduction. Fifty-six (55%) patients experienced grade 3-4 treatment-related toxicities, the most common (> 5%) being neutropenia (39%), skin rash (20%), myalgia (16%) and fatigue (16%). Seven (7%) patients discontinued treatment before completion, after a median time of 4 months (range, 1-10 months): 4 because of toxicity (arterial thrombosis in 2, respiratory failure in 1, and skin rash in 1), and 3 because of progression. Ninety-eight patients were evaluable for response, while 3 patients discontinued treatment because of toxicity before first response assessment. Overall response rate was 98%, CR rate 90% (both achieved after a median of 6 months [range, 3-22 months]), and CR rate at 30 months (CR30) was 80%. Only female sex associated with a higher CR rate (96% vs 83%, p=0.05), while no baseline characteristic associated with CR30 rate. After a median follow-up of 88 months (95% confidence interval, 84-92 months), 31 (31%) patients progressed and/or died, 7-year progression-free survival (PFS) was 63%, and 13% of patients had a PFS < 24 months (PFS24). Failure to achieve CR was the only factor associated with significantly decreased PFS (10 months vs not reached, p<0.001) and higher likelihood of PFS24 (46% vs 5%, p<0.001). No association was observed with baseline characteristics, including FLIPI and FLIPI-2 score. At most recent follow-up, transformation was reported in 3 (3%) patients, after 30, 32 and 42 months, respectively. Two (2%) patients have died, 1 of unrelated comorbid health conditions, 1 of progressive disease, and 7-year overall survival was 98%. Second cancers (excluding transformation) were diagnosed in 8 (8%) patients, after a median of 55 months (range, 3-105 months). These included: breast adenocarcinoma (2), melanoma (2), pancreatic adenocarcinoma (1), esophageal adenocarcinoma (1), and therapy-related acute myeloid leukemia. Discussion. Long-term follow-up show very favorable outcomes for patients with advanced stage FL receiving R2 as initial treatment, independent of traditional prognostic factors relevant to patients treated with chemoimmunotherapy, including FLIPI and FLIPI-2 score. Combination strategies, aimed at increasing depth of response to R2, may further improve outcomes observed with this regimen. Table. Disclosures Nastoupil: Bayer: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; TG Therapeutics: Honoraria, Research Funding; Spectrum: Honoraria. Westin:Janssen: Other: Advisory Board, Research Funding; Unum: Research Funding; Curis: Other: Advisory Board, Research Funding; 47 Inc: Research Funding; Genentech: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; Celgene: Other: Advisory Board, Research Funding; MorphoSys: Other: Advisory Board; Novartis: Other: Advisory Board, Research Funding; Kite: Other: Advisory Board, Research Funding. Wang:AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MoreHealth: Consultancy, Equity Ownership; Acerta Pharma: Consultancy, Research Funding; BioInvent: Consultancy, Research Funding; Pharmacyclics: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Juno Therapeutics: Research Funding; Dava Oncology: Honoraria; Celgene: Honoraria, Research Funding; Aviara: Research Funding; Kite Pharma: Consultancy, Research Funding; Guidepoint Global: Consultancy; VelosBio: Research Funding; Loxo Oncology: Research Funding. Neelapu:Pfizer: Consultancy; Precision Biosciences: Consultancy; Merck: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Allogene: Consultancy; Novartis: Consultancy; BMS: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Cellectis: Research Funding; Acerta: Research Funding; Karus: Research Funding; Poseida: Research Funding; Incyte: Consultancy; Cell Medica: Consultancy; Unum Therapeutics: Consultancy, Research Funding. Fowler:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: lenalidomide and rituximab are not yet FDA-approved as frontline treatment for patients with FL

Long Term Follow up of the Combination of Bortezomib with Dexamethasone as Initial Treatment for AL Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3048-3048
Author(s):  
Efstathios Kastritis ◽  
Maria Roussou ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
Constantinos Pamboukas ◽  
...  
Keyword(s):  
Initial Treatment ◽  
Cardiac Amyloidosis ◽  
Cardiac Involvement ◽  
High Dose ◽  
Al Amyloidosis ◽  
Long Term Follow Up ◽  
Organ Response ◽  
High Dose Melphalan

Abstract Abstract 3048 Until recently, patients with AL amyloidosis had limited treatment options, especially those who were not candidates for high dose therapy, those with severe cardiac involvement or patients who relapsed after initial treatment or never responded to first line alkylators with steroids. Bortezomib (B) with dexamethasone (D) has shown significant activity in patients with AL amyloidosis in patients who relapsed or even those who were refractory to initial treatment. We and others have presented data indicating that BD is active in newly diagnosed patients with AL, inducing responses rapidly but also associated with high rates of complete responses. However, data about long-term follow-up of these patients are limited. Thus, we updated a series of 24, previously untreated patients who received frontline BD. In all patients, treatment started with B at a dose of 1.3 mg/m2 on days 1, 4, 8 & 11 and D was given for 4 consecutive days at a dose of 40 mg per day (days 1–4), every 21 days for up to 6 cycles. The median age of these patients was 70 years (range 42–82) and 46% were males. The median number of involved organs was 2; heart was involved in 83% and kidneys in 63%. Fifty-seven percent were Mayo stage II and 26% were Mayo stage III while 67% had impaired ECOG performance status ≥ 2. The first patient started treatment with BD on September 2005. A median of 5 cycles of BD was given (range 1–6) and 57% of patients received the planned 6 cycles. On intent to treat and according to criteria published by Gertz et al in 2005, 77% of patients achieved a hematologic response including 36% with a hematologic CR. Most of the responses occurred after the first cycle of BD (median time to first response <1 month), while a median of two cycles of BD was needed for CR (median time to CR was 42 days, range 21–84). In 54% of patients an organ response was recorded: 47% of patients with a cardiac involvement achieved a cardiac response and 77% had a reduction of NTproBNP ≥ 30% (which was at least 300 pg/ml), while 60% of patients with a kidney involvement achieved an organ response. Three patients received high dose melphalan with autologous stem cell transplant (HDM-ASCT) after they had completed 6 cycles of BD, 2 while in CR and one in PR. All these 3 patients had achieved organ responses before ASCT. The median follow up for all patients is 31 months. Thirteen patients (54%) have died; most of them due to complications of cardiac amyloidosis and the median survival is estimated to exceed 36 months (patients who underwent ASCT were censored at the time of HDM). Baseline NT-proBNP was the most significant factor independently associated with survival. There were no differences in the baseline characteristics of patients who achieved CR compared to those who achieved a PR as best hematologic response. The median follow up for patients who achieved a CR is 31 months (range 2–55 months). One patient died early due to complications of cardiac amyloidosis, while she had achieved a CR. Among the rest of the patients who achieved a CR but did not receive HDM, all remain alive and without progression for a median of 32 months. Similarly none of the patients who received HDM has relapsed. Among patients who achieved a PR as their best response, 4 (50%) have relapsed and the median progression free survival (PFS) for these patients is 9 months and their median survival is 34 months. In conclusion, BD induces high rates of CRs, in unselected, patients with previously untreated AL amyloidosis, most of whom had features of advanced disease and elevated cardiobiomarkers. i.e. patients that may be excluded form clinical trials. The severity of cardiac involvement remains the most important prognostic factor despite the rapid responses and the high rates of hematologic CRs. It is also of interest to note that CRs may persist even in patients who did not receive any alkylating agents or consolidation with high dose melphalan. A CR is associated with improved survival and should be the primary goal of treatment in patients with AL. Our data indicate that primary treatment with bortezomib based regimens should be evaluated in a phase III trial. Disclosures: Dimopoulos: Ortho-Biotech: Honoraria; Celgene: Honoraria; Millennium: Honoraria.

Clinical features of mood disorders and mania

2012 ◽  
pp. 632-637
Author(s):  
Per Bech
Keyword(s):  
Mood Disorders ◽  
Symptom Severity ◽  
Mood States ◽  
Evidence Based ◽  
Follow Up Studies ◽  
Long Term Follow Up ◽  
Depressive Episodes

The clinical spectrum of the states of depression and mania has been described in Fig. 4.5.2.1 by the symptomatic dimensions of severity as validated by clinician-rated scales. Thus, symptom severity is a key issue of the spectrum of mood states. The spectrum of mood polarity disorders covering the longitudinal diagnosis of manic and depressive episodes is shown in Fig. 4.5.2.2. Recent research has demonstrated how important it is to recognize subthreshold states of mania and depression, as they can have a major impact on both social functioning and quality of life, since many patients with mood disorders spend much time in subthreshold disorders, i.e. cyclothymia, dysthymia, or neuroticism. While the severity spectrum of the states of mania and depression has been accepted as evidence-based, we still lack a validation of the mood polarity spectrum in long-term follow-up studies.

Endovascular treatment of basilar tip aneurysms using electrolytically detachable coils

1996 ◽  
Vol 84 (3) ◽  
pp. 393-399 ◽  
Author(s):  
Cameron G. McDougall ◽  
Van V. Halbach ◽  
Christopher F. Dowd ◽  
Randall T. Higashida ◽  
Donald W. Larsen ◽  
...  
Keyword(s):  
Initial Treatment ◽  
Content Type ◽  
Initial Treatment Period ◽  
Long Term Follow Up ◽  
Detachable Coils ◽  
Aneurysm Occlusion ◽  
Permanent Morbidity ◽  
Fine Print

✓ Preliminary experience using electrolytically detachable coils to treat basilar tip aneurysms in 33 patients is described. The most frequent presentation was subarachnoid hemorrhage (SAH) in 23 patients. All patients were referred after neurosurgical assessment and exclusion as candidates for surgical clipping of their aneurysms. At the time of initial treatment complete aneurysm occlusion was achieved in seven (21.2%) of 33 patients. In 17 of the patients (51.5%), greater than 90% but less than 100% aneurysm occlusion was achieved. Angiographic follow up (mean 11.7 months) was available in 19 patients. At follow-up angiography four (21%) of 19 aneurysms were 100% occluded and 12 (63.2%) of 19 were more than 90% but less than 100% occluded. The mean clinical follow-up time in treated patients surviving beyond the initial treatment period is 15 months. One patient suffered major permanent morbidity from thrombosis of the basilar tip region a few hours after coil placement. One patient treated following SAH experienced further hemorrhage 6 months later. No other patient suffered direct or indirect permanent morbidity as a consequence of this method of treatment. The authors believe that this technique is a reasonable alternative for patients who are not candidates for conventional surgical treatment or in whom such treatment has failed. This study's follow-up period is brief and greater experience with long-term follow-up study is mandatory.

Laser Peripheral Iridoplasty as Initial Treatment of Acute Attack of Primary Angle-Closure: A Long-Term Follow-up Study

2002 ◽  
Vol 11 (6) ◽  
pp. 484-487 ◽  
Author(s):  
Jimmy S. M. Lai ◽  
Clement C. Y. Tham ◽  
John K. H. Chua ◽  
Agnes S. Y. Poon ◽  
Dennis S. C. Lam
Keyword(s):  
Initial Treatment ◽  
Acute Attack ◽  
Angle Closure ◽  
Follow Up Study ◽  
Primary Angle Closure ◽  
Long Term Follow Up

scholarly journals Long-Term Follow-Up of Accelerated Transepithelial Corneal Crosslinking for Post-LASIK Ectasia: A Pilot Prospective Observational Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Mi Tian ◽  
Xiaoyu Zhang ◽  
Weijun Jian ◽  
Ling Sun ◽  
Yang Shen ◽  
...  
Keyword(s):  
Observational Study ◽  
Repeated Measures ◽  
Prospective Observational Study ◽  
Statistical Significance ◽  
Corneal Thickness ◽  
Corneal Crosslinking ◽  
Epithelial Thickness ◽  
Long Term Follow Up

Background: Keratectasia after corneal refractive surgery is a rare but serious postoperative complication, and reports on accelerated transepithelial corneal crosslinking (ATE-CXL)-based treatment of patients with post-laser-assisted in situ keratomileusis (LASIK) ectasia are limited. Therefore, this study evaluated the long-term efficacy and safety of ATE-CXL for progressive post-LASIK ectasia.Methods: This prospective observational study was conducted at the Eye and ENT Hospital, Fudan University, Shanghai, China, and 25 eyes from 25 patients with post-LASIK ectasia undergoing ATE-CXL were examined. Clinical examinations were conducted preoperatively and postoperatively to assess parameters such as manifest refraction, corrected distance visual acuity (CDVA), endothelial cell density; keratometry, corneal thickness, posterior elevation and topometric indices were measured using Pentacam; sectoral pachymetry and epithelial thickness were evaluated using optical coherence tomography. A paired t-test, Wilcoxon rank-sum test, Kruskal-Wallis test, and repeated measures analysis of variance were used for statistical analysis.Results: Participants were examined for an average of 46 months. No severe complications occurred during or after ATE-CXL. CDVA improved from 0.25 ± 0.31 preoperatively to 0.15 ± 0.17 postoperatively (p = 0.011). Maximum keratometry decreased from 55.20 ± 8.33 D to 54.40 ± 7.98 D, with no statistical significance (p = 0.074), and the central corneal thickness increased from 414.92 ± 40.96 μm to 420.28 ± 44.78 μm (p = 0.047) at the final follow-up. Posterior elevation, pachymetry, and epithelial thickness remained stable (p &gt; 0.05) throughout the follow-up. No significant differences were noted in topometric indices, except the central keratoconus index, which decreased significantly (p &lt; 0.001) at the final follow-up.Conclusion: Improvements in CDVA and stabilization in corneal keratometry and posterior elevation after ATE-CXL were noted at the 46-months follow-up, demonstrating that ATE-CXL is a safe and effective treatment for progressive post-LASIK ectasia.

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