Antidepressant effects of dexmedetomidine compared with ECT in patients with treatment-resistant depression.

OBJECTIVE: This pilot study was designed to investigate the antidepressant effects of dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, in patients with treatment-resistant depression (TRD). The antidepressant effects of dexmedetomidine was compared with ECT, which is widely used in clinical practice for treatment of patients with TRD. METHODS: Seventy six patients with TRD were randomly assigned to receive 10 sessions of DEX infusions or electroconvulsive therapy (ECT) treatment. The primary outcome was the changes of depression severity determined by the improvement of 24-item Hamilton Depression Rating Scale (HDRS-24). The second outcomes were the rates of therapeutic response (reduction in HDRS-24 ≥ 50 %) and remission (HDRS-24 ≤ 10 and reduction in HDRS-24 ≥ 60 %) at posttreatment and after 3 months of follow-up visits. RESULTS: We found that 10 sessions of DEX infusions or ECT treatments significantly improved HDRS-24 scores at posttreatment and after 3 months of follow-up visits compared with the baseline. In addition, there was no significant difference between DEX infusions and ECT treatments regarding HDRS-24 at these evaluating points. Furthermore, the depression severity dropped to mild after 2 sessions of DEX infusion. In contrast, at least 6 sessions of ECT treatment were needed to achieve a same level. Finally, the rates of therapeutic response and remission were comparable between the two groups. No serious adverse events were observed. CONCLUSIONS: Based on current published evidence, we conclude that DEX exhibits rapid and durable antidepressant properties similar to ECT but with fewer side effects.

Efficacy and Safety of Long-Term Corticosteroid Monotherapy in 26 Cases of Nephrotic Syndrome with Biopsy-Proven Membranous Nephropathy Induced by Seronegative Hepatitis B Virus-Associated Glomerulonephritis.

BACKGROUND: Hepatitis B virus-associated glomerulonephritis (HBV-GN) can occur in patients with negative HBV serological antigens. Little is known about the treatment of seronegative HBV-GN (sn HBV-GN). The aim of this prospective study was to evaluate the efficacy and safety of corticosteroids in the treatment of sn HBV-GN. METHODS: Twenty-six patients with nephrotic syndrome induced by seronegative HBV-associated membranous nephropathy were enrolled. The patients were given methylprednisolone (0.8 mg/kg/day) for 12-24 weeks, tapered by a 2-mg reduction every 1-3 months. Patients were followed up for 6-36 months. Complete remission (CR) was defined as proteinuria <0.3 g/24 h. Partial remission (PR) was defined as proteinuria of 0.3-3.5 g/24 h that was reduced ≥50% of the baseline level. RESULTS: The effective remission (including CR and PR) rates of nephrotic syndrome were 23.1%, 61.5%, 73.1%, 76.2%, 90.5%, and 81.0%, respectively, after 1, 3, 6, 12, 24, and 36 months. Nineteen patients achieved effective remission after 11.68 ± 7.15 months. The level of serum albumin improved from 24.34 ± 6.71 g/L at baseline to 39.61 ± 7.45 g/L at the 36th month significantly. After treatment, the level of serum Cr was similar to the baseline. Only 2 patients relapsed. The primary adverse reaction was infection. None of the patients showed evidence of HBV replication. CONCLUSION: The long-term middle-dose corticosteroid therapy without antiviral drugs is effective and safe for membranous sn HBV-GN patients. For sn HBV-GN patients, the monitoring of HBV DNA and HBV markers in the serum is necessary during the corticosteroid monotherapy. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR1900022518).

Dynamic and specific immune responses against multiple tumor antigens were elicited in patients with hepatocellular carcinoma after cell-based immunotherapy.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in China and frequently occurs with chronic hepatitis B virus infection. To investigate whether cell-based cancer immunotherapy induces tumor specific immune responses in patients with HCC and provides clinical benefits, as well as to elucidate the most immunogenic tumor associated antigens (TAAs), multiple antigen stimulating cellular therapy (MASCT) was applied in addition to standard of care. METHODS: Mature dendritic cells (DCs) and activated T cells prepared for MASCT were generated from autologous peripheral blood mononuclear cells (PBMCs). DCs were loaded with a peptide pool of multiple HCC-related tumor antigens, and T cells were stimulated by these DCs. RESULTS: Thirteen patients with HCC received repeated MASCT after tumor resection during which their immune responses were examined. After three courses of MASCT, the frequency of regulatory T cells in the patients' PBMCs significantly decreased (p < 0.001), while the antigen peptide pool-triggered T cell proliferation (p < 0.001) and IFNγ production (p = 0.001) were significantly enhanced. The specific T cell responses against each antigen in the pool were detected in 11 patients, but with individualized distinct patterns. The most immunogenic TAAs for HCC are survivin, CCND1, and RGS5. Moreover, the antigen-specific immune responses observed in tumor-free patients' PBMCs were significantly stronger than that in the patients with recurrence (p = 0.037). CONCLUSIONS: Our study demonstrates that MASCT is well-tolerated by patients with HCC and elicits strong and dynamic immune responses specifically against multiple tumor associated antigens, which may correlate with clinical outcomes.