Long-term tolerability, safety and efficacy of rituximab in neuromyelitis optica spectrum disorder: a prospective study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a B-cell-mediated disease with autoimmunity towards the astrocyte water channel aquaporin-4 (AQP-4) in the central nervous system. OBJECTIVE: To assess the long-term safety and efficacy in NMOSD patients receiving maintenance therapy with B-cell-depleting agent rituximab for more than 2 years. METHOD: NMOSD patients were included prospectively from 2014 to 2018 and received continuous cycles of rituximab infusions biannually. Incidence of adverse events (AE), serious AEs (SAE), and infusion-related AEs were evaluated through monthly phone calls and neurological examination every 4 months. RESULTS: A total of 44 NMOSD patients were included, of those 30 were treatment naive (68%). The mean age was 37.2 years with 79.5% females. With overall observation period of 31.6 ± 7.3 months (24-48 months), tolerability was assessed as satisfactory in most cases. We observed infusion reactions (mostly mild) in 31.8% of patients and 31.8% never experienced any AEs after a mean 5.1 cycles of rituximab therapy. Rituximab was also beneficial in terms of improvement in relapse rate (from 0.26 ± 0.54 to 0, P = 0.003) and Expanded Disability Status Scale (from 4.1 ± 1.8 to 3.1 ± 1.8, P < 0.001). Stratification according to AQP4-IgG serostatus showed no difference between groups. CONCLUSION: Rituximab treatment is well tolerated, safe, and efficacious with a minor risk of mild infusion reactions for NMOSD patients.

Decreased serum levels of interleukin-35 among multiple sclerosis patients may be related to disease progression.

The regulatory role of interleukin (IL) -35 in the immunopathogenesis of multiple sclerosis (MS) is suggested in very few studies. We aimed to measure serum levels of IL-35 among clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) patients and evaluate the associations between this cytokine and the disease clinical course. This cross-sectional study was conducted during 2017 in a referral university clinic. Forty patients and 40 healthy controls were included in the study. The level of IL-35 in the serum of all subjects was determined by ELISA. Serum level of IL-35 was reduced (p = 0.003) in RRMS in comparison with healthy controls. Moreover, the mean serum level of IL-35 among new cases (diagnosed within the 6 months prior to the study) decreased compared to healthy controls but it was not statistically significant (P=0.059). The mean serum level of IL-35 was significantly higher in new cases compared with other cases (p=0.048). Overall, we found decreased serum level of IL-35 among RRMS patients compared to the healthy controls. Our finding provides a view of the possible role of IL-35 in MS pathogenesis and the potential therapeutic targets.

Quality of Life, Anxiety and Depression in Patients with Differentiated Thyroid Cancer under Short Term Hypothyroidism Induced by Levothyroxine Withdrawal.

BACKGROUND: We studied quality of life (QOL), anxiety, and depression in patients with differentiated thyroid cancer (DTC) either during treatment with levothyroxine or during withdrawal from levothyroxine when whole-body scanning (WBS) needed to be performed. METHODS: DTC patients projected to undergo WBS were included in the study. They were studied at two time-points - the day before levothyroxine withdrawal, and one month after levothyroxine withdrawal. They were asked to fill WHOQOL-Bref, BDI-II, and HADS questionnaires at both time-points, and blood samples were taken to measure TSH, Tg, and TgAb levels. RESULTS: Twenty-nine subjects (11 males) with a mean age of 42.6 ± 14.1 years entered the study. From the first to second time-point, the mean TSH level increased from 0.73 to 106.9 U/ml and the mean Tg level increased from 20.4 to 63.6 ng/ml. QOL scores decreased in four dimensions (physical health: 67.8 to 25.7; psychological: 58.9 to 38.9; social relationship: 67.5 to 56; and environment: 57.2 to 48.8). Patients also felt more depressed (48.3% to 93.2%) and anxious (65.5% to 89.6%). All changes were statistically significant (p < 0.005). CONCLUSION: We found decreased QOL after short-term hypothyroidism, especially in physical health and psychological dimensions. We also found that patients became significantly depressed and anxious after levothyroxine withdrawal. Our findings suggest that alternative therapies, such as those employing rhTSH, should be considered for these patients. Psycho-oncological support might also be useful in helping them overcome their symptoms during short-term hypothyroidism; however, considering the reversibility of their symptoms, supportive care might be more effective.Key words: quality of life - anxiety - depression - thyroid cancer - hypothyroidism - levothyroxine - whole body scanning.

Differentiated thyroid cancer in Iran - initial observations, histological features, management of the disease, and tumor recurrence: A review of 1689 cases.

AIM: The main objective of this study was to define some histopathological aspects of differentiated thyroid cancer (DTC), describe the disease management, and evaluate potential predicting factors for tumor recurrence in Iran. MATERIALS AND METHODS: Medical records of 1689 patients of DTC treated over a 15-year period at a referral hospital located in the central region of Iran were reviewed retrospectively. RESULTS: The female/male ratio was 3.78. The mean size of tumors was 23.35 mm. Most patients had papillary thyroid cancer (PTC) followed by follicular thyroid cancer (FTC) (83% and 5.5%, respectively). Lymph node involvement was seen in 27.6% of patients, and 3.6% of them had distant metastasis. Tumor recurrence was reported in 36.4% of patients. Higher stages of cancer, presence of lymph node involvement, presence of distant metastasis, larger tumor size, history of goiter, and higher doses of 131-Iodine at the first admission were associated with more chance of recurrence (P < 0.05). Comparing features of PTC and FTC, we found a more invasive behavior in FTC patients, including more capsular and near tissue invasion, higher stages of cancer, more frequent distant metastasis, and larger tumor size. CONCLUSION: This study provides useful information on characteristics of DTC, its management, and some prognostic factors. Our findings suggest that higher stages of cancer at diagnosis, presence of lymph node involvement, presence of distant metastasis, larger tumor size, history of goiter, and higher doses of 131-iodine administered at the first admission are associated with more chance of tumor recurrence. Furthermore, we found that FTC follows a more aggressive behavior and recommends clinicians to handle FTC patients more cautiously.