Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus.

OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. CONCLUSION: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

Effect of high-field iMRI guided resection in cerebral glioma surgery: A randomized clinical trial.

BACKGROUND: Extent of resection (EOR) in glioma contributes to longer survival. The purpose of NCT01479686 was to prove whether intraoperative magnetic resonance imaging (iMRI) increases EOR in glioma surgery and benefit survival. METHODS: Patients were randomized (1:1) to receive the iMRI (n = 161) or the conventional neuronavigation (n = 160). The primary endpoint was gross total resection (GTR); secondary outcomes reported were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 188 high-grade gliomas (HGGs) and 133 low-grade gliomas (LGGs) were enrolled. GTR was 83.85% in the iMRI group vs. 50.00% in the control group (P < 0.0001). In 321 patients, the median PFS (mPFS) was 65.12 months in the iMRI group and 61.01 months in the control group (P = 0.0202). For HGGs, mPFS was improved in the iMRI group (19.32 vs. 13.34 months, P = 0.0015), and a trend of superior OS compared with control was observed (29.73 vs. 25.33 months, P = 0.1233). In the predefined eloquent area HGG subgroup, mPFS, and mOS were 20.47 months and 33.58 months in the iMRI vs. 12.21 months and 21.16 months in the control group (P = 0.0098; P = 0.0375, respectively). From the exploratory analyses of HGGs, residual tumor volume (TV) < 1.0 cm3 decreased the risk of survival (mPFS: 18.99 vs. 9.43 months, P = 0.0055; mOS: 29.77 vs. 18.10 months, P = 0.0042). LGGs with preoperative (pre-OP) TV > 43.1 cm3 and postoperative (post-OP) TV > 4.6 cm3 showed worse OS (P= 0.0117) CONCLUSIONS: It showed that iMRI significantly increased EOR and indicated survival benefits for HGGs, particularly eloquent HGGs. Residual TV in either HGGs or LGGs is a prognostic factor for survival.

Integrated Diffusion Tensor Imaging and Renal Parenchymal Volume for Early Detection and Grading of Split Renal Functional Impairment in Lupus Nephritis.

RATIONALE AND OBJECTIVES: To investigate the effectiveness of combining split diffusion tensor imaging (DTI) measurements with split renal parenchymal volume (RPV) for assessing split renal functional impairment in patients with lupus nephritis (LN). MATERIALS AND METHODS: Seventy-four participants [48 LN patients and 26 healthy volunteers (HV)] were included in the study. All participant underwent conventional MR and DTI (b = 0, 400, and 600 s/mm2) examinations using a 3.0 T MRI scanner to determine the split renal DTI measurements and split RPV. In LN patients, renography glomerular filtration rate (rGFR) was measured using 99mTc-DTPA scintigraphy based on Gates' method, serving as the reference standard to categorize all split kidneys of LN patients into LN with mild impairment (LNm, n = 65 kidneys) and LN with moderate to severe (LNms, n = 31 kidneys) groups according to the threshold of 30 ml/min in spilt rGFR. All statistical analyses were performed using SPSS 25.0 and MedCalc 20.0 software packages. RESULTS: Only split medullary fractional anisotropy (FA) and the product of split medullary FA and RPV could distinguish pairwise subgroups among the HV and each LN subgroup (all p < 0.05). ROC curve analysis demonstrated that split medullary FA (AUC = 0.866) significantly outperformed other parameters in differentiating HV from LNm groups, while the product of split medullary FA and split RPV was superior in distinguishing LNm and LNms groups (AUC = 0.793) than other parameters. The combination of split medullary FA and split RPV showed best correlation with split rGFR (r = 0.534, p < 0.001). CONCLUSION: Split medullary FA, and its combination with split RPV, are valuable biomarkers for detecting early functional changes in renal alterations and predicting disease progression in patients with LN.

Convergence of the arcuate fasciculus and third branch of the superior longitudinal fasciculus with direct cortical stimulation-induced speech arrest area in the anterior ventral precentral gyrus.

OBJECTIVE: The objective was to identify the correspondence between the anterior terminations of the arcuate fasciculus (AF) and third branch of the superior longitudinal fasciculus (SLF-III) and the intraoperative direct cortical electrical stimulation (DCS)-induced speech arrest area. METHODS: The authors retrospectively screened 75 glioma patients (group 1) who received intraoperative DCS mapping in the left dominant frontal cortex. To minimize the influence of tumors or edema, we subsequently selected 26 patients (group 2) with glioma or edema not affecting Broca's area, the ventral precentral gyrus (vPCG), and the subcortical pathways to generate DCS functional maps and to construct the anterior terminations of AF and SLF-III with tractography. Next, a grid-by-grid pairwise comparison was performed between the fiber terminations and the DCS-induced speech arrest sites to calculate Cohen's kappa coefficient (κ) in both groups 1 and 2. Finally, the authors also demonstrated the distribution of the AF/SLF-III anterior projection maps obtained in 192 healthy participants (group 3) and subsequently correlated these with the speech arrest sites in group 2 to examine their validity in predicting speech output area. RESULTS: The authors found that speech arrest sites were substantially consistent with SLF-III anterior terminations (group 1, κ = 0.64 ± 0.03; group 2, κ = 0.73 ± 0.05) and moderately consistent with AF (group 1, κ = 0.51 ± 0.03; group 2, κ = 0.49 ± 0.05) and AF/SLF-III complex (group 1, κ = 0.54 ± 0.03; group 2, κ = 0.56 ± 0.05) terminations (all p < 0.0001). The DCS speech arrest sites of the group 2 patients mainly (85.1%) emerged at the anterior bank of the vPCG (vPCGa). In group 3, both terminations of AF and SLF-III converged onto the vPCGa, and their terminations well predicted the DCS speech output area of group 2 (AF, area under the curve [AUC] 86.5%; SLF-III, AUC 79.0%; AF/SLF-III complex, AUC 86.7%). CONCLUSIONS: This study supports the key role of the left vPCGa as the speech output node by showing convergence between speech output mapping and anterior AF/SLF-III connectivity in the vPCGa. These findings may contribute to the understanding of speech networks and could have clinical implications in preoperative surgical planning.

Phenotypical changes and clinical significance of CD4+/CD8+ T cells in SLE.

OBJECTIVE: T cells display significant phenotypical changes and play multiple roles in promoting the immune response in SLE. The frequencies of T cell subpopulations in SLE are still not well understood. To better understanding the phenotypic abnormalities of T cells in SLE will help us to clarify disease immunopathology and to find promising biomarkers for disease monitoring and control. METHODS: Peripheral blood CD4+ and CD8+ T cells and their subsets were determined by flow cytometry. Forty-one active SLE patients were selected, including 28 new-onset patients and 13 relapsing patients. One hundred healthy controls (HCs) were enrolled as the control group. The percentages of these cell subsets between patients with SLE and HCs and their relationships with disease activity and autoantibody titers were analysed. Thirteen of 28 new-onset SLE patients were assessed before and after treatment. The changes in the frequencies of these cell subsets and their relationships with renal response were analysed. RESULTS: There was a broad range of anomalies in the proportion of T cell subsets in patients with SLE compared with that of the HCs. Compared with the HCs, a higher frequency of memory T cells and a lower frequency of naïve T cells were noted in patients with SLE. In addition, an imbalance of CD28+ and CD28- cells in CD4+ T cells was observed in patients with SLE. We found that the expanded CD4+CD28- T cells did not decrease after treatment in patients who had impaired renal responses. It was very interesting to exhibit a negative correlation in the frequency between the CD4+CD28- T cells and T regulatory (Treg) cells and a positive correlation between the frequency of CD4+CD28+ T cells and Treg cells in this study. Increased CD8+HLADR+ T cell and CD8+CD38+HLADR+ T cell counts were observed in patients with SLE, suggesting an impaired cytotoxic capacity of CD8+ T cells in SLE. Additionally, we found that CD8+CD38+HLADR+ T cells were closely associated with disease activity, autoantibody titres and renal prognosis. CD4+ CXCR5-PD1+ T cells were expanded in patients with SLE in this study and were associated with disease activity in SLE. Th1 (T helper type 1) cells and Treg cells were decreased, but frequencies of T follicular helper (Tfh) cells, Th2 cells, Th17 cells and Tfh17 cells were increased. A strong correlation between Th17 cells and Tregs with renal involvement was observed in this study. CONCLUSION: The proportions of CD4+CD28- T cells, CD4+CXCR5-PD1+ T cells, CD8+HLADR+ T cells and CD8+CD38+HLADR+ T cells increased in patients with SLE and could be associated with disease activity and renal prognosis.

Inflammatory markers and risk factors of RA patients with depression and application of different scales in judging depression.

To evaluate the association of inflammatory markers and depression in RA patients and the risk factors in RA with depression, a cross-sectional study was conducted in a cohort of RA patients from southern China.Two hundred-fifteen RA patients were enrolled. The demographic and disease-related characteristics were recorded and inflammatory markers in sera were measured. RA patients were guided to fill out PHQ-9 scale by themselves, the psychological state was evaluated by psychiatry experts and graded according to the HAMD-17 scale. The consistency of the two scales in judging depression was evaluated. RA with depression group had HAMD-17 scores greater than 7. The levels of CRP, ESR, fibrinogen, SAA, IL-2, IL-6, TNF-α, IFN-γ, IL-4, and IL-10 were measured and compared. Logistic regression analysis was performed to find the risk factors of RA with different depression levels. One hundred-five (48.84%) RA patients had HAMD-17 scores greater than 7. High consistency was found between HAMD-17 and PHQ-9 in predicting depression. RA patients with depression were more likely to have tender joints, lower income, no employment, higher disease activity, joint deformities and glucocorticoid treatment. The depressed RA patients had higher serum levels of IL-6, CRP, fibrinogen, and SAA. IL-6, CRP, fibrinogen, and SAA were positive correlated with depression in RA patients. PHQ-9 can replace HAMD-17 in clinical application to judge depression.

Can metformin relieve tibiofemoral cartilage volume loss and knee symptoms in overweight knee osteoarthritis patients? Study protocol for a randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Osteoarthritis (OA) is the most common joint disease, and is most frequently seen in the knees. However, there is no effective therapy to relieve the progression of knee OA. Metformin is a safe, well-tolerated oral medication that is extensively used as first-line therapy for type 2 diabetes. Previous observational studies and basic researches suggested that metformin may have protective effects on knee OA, which needs to be verified by clinical trials. This study, therefore, aims to examine the effects of metformin versus placebo on knee cartilage volume loss and knee symptoms in overweight knee OA patients by a randomized controlled trial over 24 months. METHODS: This protocol describes a multicenter, randomized, double-blind, and placebo-controlled clinical trial aiming to recruit 262 overweight knee OA patients. Participants will be randomly allocated to the two arms of the study, receiving metformin hydrochloride sustained-release tablets or identical inert placebo for 24 months (start from 0.5 g/day for the first 2 weeks, and increase to 1 g/day for the second 2 weeks, and further increase to 2 g/day for the remaining period if tolerated). Primary outcomes will be changes in tibiofemoral cartilage volume and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score over 24 months. Secondary outcomes will be changes in visual analogue scale (VAS) knee pain, tibiofemoral cartilage defects, effusion-synovitis volume, and tibiofemoral bone marrow lesions maximum size over 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per-protocol analyses will be performed as the secondary analyses. DISCUSSION: If metformin is proved to slow knee cartilage volume loss and to relieve knee symptoms among overweight knee OA patients, it will have the potential to become a disease modifying drug for knee OA. Metformin is a convenient intervention with low cost, and its potential effects on slowing down the structural progression and relieving the symptoms of knee OA would effectively reduce the disease burden worldwide. TRIAL REGISTRATION: ClinicalTrials. gov NCT05034029 . Registered on 30 Sept 2021.

Increased eEF2K Promotes Glycolysis and Aggressive Behaviors of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

Objective: Aggressive phenotype and abnormal glycolytic metabolism of fibroblast-like synoviocytes (FLSs) are essential to joint inflammation and damage in rheumatoid arthritis (RA). Eukaryotic elongation factor-2 kinase (eEF2K) is a negative regulator of protein synthesis and has been shown to play an important role in regulating various cellular processes and promoting glycolysis in tumor cells. However, the role of eEF2K in regulating the pathogenic FLS behaviors is unknown. Methods: A specific inhibitor of eEF2K, NH125, and siRNA were used to evaluate the role of eEF2K on RA FLSs in vitro. Collagen-induced arthritis (CIA) mice were used to evaluate the in vivo effect of eEF2K. Cell migration, invasion of RA FLSs were assessed by transwell or wound healing assays. Relative changes of cytokines were analyzed by quantitative real-time PCR, western blot and ELISA. Results: Herein, we found an increased expression of eEF2K in synovial tissues and FLSs of RA patients. eEF2K knockdown by siRNA or treatment with NH125, an inhibitor of eEF2K, significantly reduced inflammation, migration/invasion, glucose uptake and lactate productions. eEF2K knockdown suppressed TNF-α-induced activation of NF-κB and AKT pathways in RA FLSs. Lactate reversed the inhibitory effect of eEF2K knockdown on inflammation and migration of RA FLSs. Moreover, lactate was also involved in eEF2K-mediated activation of NF-κB and AKT. NH125 treatment attenuated the severity of arthritis in collagen-induced arthritis mice. Conclusion: eEF2K inhibition suppressed glycolysis and aggressive behaviors of RA FLS, which indicated that targeting eEF2K may be a new strategy for the treatment of RA.

High-Fidelity Patient Simulation Incorporated Into a Flipped Classroom Improves Students' Long-Term Knowledge Retention of Acute Organophosphorus Pesticide Poisoning.

INTRODUCTION: The flipped classroom (FC) approach and high-fidelity patient simulation (HFPS) training have shown promising effects in short-term acquisition or long-term retention of knowledge in medical education. In this study, we aimed to explore the incorporation of HFPS into the FC and the impact on the long-term (3 months after classes) knowledge retention of medical undergraduate students learning about acute organophosphorus pesticide poisoning (AOPP). METHODS: Eighty-two fifth-year medical students were randomly divided into an HFPS group (HG, n = 40) and an FC group (FG, n = 42). A postclass quiz and preinternship quiz were performed to assess the short-term knowledge acquisition and long-term (3 months after classes) knowledge retention of both groups of students. Feedback questionnaires were administered immediately after the class and before the internship to assess the students' self-perceived competency. RESULTS: In the postclass quiz, the scores achieved by the students from the HG and FG were 15.58 ± 2.69 and 14.62 ± 2.19, respectively. No significant difference was found between the 2 groups (P = 0.19). In the preinternship quiz, the scores achieved by the students from the HG (14.50 ± 2.16) were significantly higher than those achieved by the students from the FG (11.40 ± 2.07, P < 0.001). There was no significant difference between the postclass quiz and preinternship quiz scores achieved by the HG students (P = 0.05). However, scores in the preinternship quiz showed a significant decline compared with the postclass quiz for the FG students (P < 0.001). Students in the HG gave significantly higher scores for self-perceived confidence in dealing with AOPP patients in the forthcoming internship on the postclass and preinternship questionnaires. CONCLUSIONS: The incorporation of HFPS into the FC approach could improve students' long-term knowledge retention of AOPP and enhance their confidence in caring for these patients in their internship.

Large-scale EEG neural network changes in response to therapeutic TMS.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an effective therapy for patients with treatment-resistant depression. TMS likely induces functional connectivity changes in aberrant circuits implicated in depression. Electroencephalography (EEG) "microstates" are topographies hypothesized to represent large-scale resting networks. Canonical microstates have recently been proposed as markers for major depressive disorder (MDD), but it is not known if or how they change following TMS. METHODS: Resting EEG was obtained from 49 MDD patients at baseline and following six weeks of daily TMS. Polarity-insensitive modified k-means clustering was used to segment EEGs into constituent microstates. Microstates were localized via sLORETA. Repeated-measures mixed models tested for within-subject differences over time and t-tests compared microstate features between TMS responder and non-responder groups. RESULTS: Six microstates (MS-1 - MS-6) were identified from all available EEG data. Clinical response to TMS was associated with increases in features of MS-2, along with decreased metrics of MS-3. Nonresponders showed no significant changes in any microstate. Change in occurrence and coverage of both MS-2 (increased) and MS-3 (decreased) correlated with symptom change magnitude over the course of TMS treatment. CONCLUSIONS: We identified EEG microstates associated with clinical improvement following a course of TMS therapy. Results suggest selective modulation of resting networks observable by EEG, which is inexpensive and easily acquired in the clinic setting.

Flipped Classroom Approach Used in the Training of Mass Casualty Triage for Medical Undergraduate Students.

OBJECTIVE: The aim of this study was to explore the application of the flipped classroom approach in the training of Mass Casualty Triage (MCT) to medical undergraduate students. METHODS: In this study, 103 fourth-year medical students were randomly divided into a Flipped Classroom (FC) group (n = 51) and a Traditional Lecture-based Classroom (TLC) group (n = 52). A post-class quiz, simulated field triage (SFT) and feedback questionnaires were performed to assess both groups of students for their learning of the course. RESULTS: In the post-quiz, the median (IQR) scores achieved by students from the FC and TLC groups were 42(5) and 39(5.5), respectively. Significant differences were found between the two groups. In the SFT, overall triage accuracy was 67.06% for FC, and 64.23% for TLC students. Over-triage and under-triage errors occurred in 18.43% and 14.50% of the FC group, respectively. The TLC group had a similar pattern of 20.77% over-triage and 15.0% under-triage errors. No significant differences were found regarding overall triage accuracy or triage errors between the two groups. CONCLUSIONS: The FC approach could enhance course grades reflected in the post-quiz and improve students' satisfaction with the class. However, there was no significant difference of competency between the two groups demonstrated in the SFT exercise.

New Trends in Pharmacological Treatments for Osteoarthritis.

Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.

IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis.

Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Currently, both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear. In this study, we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A (IL-17) stimulation in SLE patients and lupus mice. Using a humanized lupus mouse model, we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs. Moreover, long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+ subsets among IL-17 receptor-expressing plasma cells. Lupus mice deficient in IL-17 or IL-17 receptor C (IL-17RC) exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage, while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice. In reconstituted chimeric mice, IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells. Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization. Together, our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis, which may provide new therapeutic strategies for the treatment of SLE.

Attenuation of pristimerin on TNF-α-induced endothelial inflammation.

OBJECTIVE: Pristimerin is known to have anti-cancer and anti-inflammatory activities; however, its therapeutic mechanism has not been described. In this study, to investigate the therapeutic mechanism of pristimerin, we examined the effect of pristimerin on TNF-α-induced endothelial inflammatory response both in vitro and in vivo. METHODS: Leukocyte-endothelium Adhesion Assay was use to evaluate the endothelial cell-monocyte interaction. Western blotting was used to confirm protein expression. NF-κB p65 nuclear translocation in endothelial cells was detected using immunofluorescent microscopy. In vivo leukocyte infiltration was evaluated using acute lung inflammation model. RESULTS: Pristimerin profoundly inhibited TNF-α-induced adhesion of monocytes to human endothelial cells and the leukocyte transmigration. Pristimerin dramatically inhibited the expression of TNF-α-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1)). Pristimerin suppressed the penetration of the leukocyte in the acute lung injury mice model. Furthermore, pristimerin also suppressed the TNF-α-activated Nuclear factor kappa B (NF-κB) activation. CONCLUSIONS: Pristimerin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of NF-κB activation, which may have a potential therapeutic effects for inflammatory vascular diseases.

Effect of Previous Electroconvulsive Therapy on Subsequent Response to Transcranial Magnetic Stimulation for Major Depressive Disorder.

OBJECTIVES: Patients with major depressive disorder (MDD) who received electroconvulsive therapy (ECT) often seek transcranial magnetic stimulation (TMS) therapy as a less invasive treatment option. How prior history of ECT and its responsiveness may affect TMS treatment outcomes for MDD is unclear. We aim to contribute evidence to this important clinical question. MATERIALS AND METHODS: Retrospective naturalistic TMS treatment data from n = 257 MDD patients. Three sets of analyses were conducted: History of past exposure to ECT (n = 71, "+ECT" vs. n = 186 ECT-naïve, "-ECT") was examined as a potential predictor of TMS outcomes (measured by two self-report scales); A subset of n = 38 +ECT patients with adequate ECT trials in current depression episode were compared with -ECT patients blindly matched on clinical variables associated with TMS outcomes; for a subset with available data, TMS outcomes were explored in relation to positive/negative response to prior ECT. RESULTS: Compared to -ECT, +ECT patients more likely had past psychiatric hospitalizations (p < 0.01) and were more severely depressed at baseline (p = 0.07). Response (p = 0.07) and remission (p = 0.02) rates were higher in -ECT than +ECT groups on one scale. However, comparison between the subsets (n = 38 each) matched on confounding factors did not find history of ECT to be a significant independent predictor of TMS outcomes. Differential responsiveness to ECT and ECT treatment characteristics did not significantly impact TMS outcomes. CONCLUSIONS: Although limited by the retrospective nature of this analysis, the results suggest that history of the past ECT, regardless of responsiveness to ECT, may not independently portend differential TMS treatment outcomes.