The efficiency and safety of low-dose apatinib combined with oral vinorelbine in pretreated HER2-negative metastatic breast cancer.

BACKGROUND: Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. METHODS: This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. RESULTS: The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). CONCLUSION: Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

Comparison of microwave alone and combined with ethanol ablation for different types of benign mixed thyroid nodules.

OBJECTIVE: To evaluate the efficacy and safety of microwave ablation (MWA) plus ethanol ablation (EA) for different types of benign mixed thyroid nodules. METHODS: A total of 81 patients with 81 benign mixed thyroid nodules were enrolled into the study; 39 were divided to the MWA group and 42 to the combined group (MWA combined with EA). Nodule ablation rate, volume reduction rate (VRR) and surgical complications of all patients were analyzed before and after treatment. RESULTS: The mean ablation rate were 86.49 ± 6.68% and 90.09 ± 5.79% in the microwave and combined groups respectively, and the ablation rate of nodule decreased as the nodule volume increased. For nodules ≥15 ml in volume, the mean ablation rate of the combined group was higher than that of the microwave group (all P < 0.05). The mean VRR at 12 months postoperatively was 89.58 ± 4.32% in the microwave group and 92.92 ± 3.49% in the combined group, showing statistical significantly different between both arms (P = 0.001). The combined group decreased in volume more significantly than the microwave group for nodules with 20-50% or 50-80% cystic proportions or >15 ml in volume (all P < 0.05). The complication rate was 23.08% and 2.38% respectively. CONCLUSION: MWA combined with EA is more effective than MWA for treating mixed thyroid nodules. MWA combined with EA may be the first approach for nodules with >20% cystic proportions or volume >15 ml.

A comparative analysis of antidepressant and anti-suicidal effects of repeated ketamine infusions in elderly and younger adults with depression.

OBJECTIVES: This study aims to investigate the differences in safety and antidepressant effects of multi-infusion ketamine treatment between elderly and young adults with depression. METHODS: The safety, antidepressant, and anti-suicidal effects of multi-infusion ketamine were compared between 19 elderly (≥50 years) and 116 younger (<50 years) adults with depression; all were treated with six ketamine infusions (0.5 mg/kg). Montgomery-Åsberg Depression Rating Scale (MADRS) was used to measure the depressive symptoms, and suicidal ideation was measured with Beck Scale for Suicide Ideation (SSI)-part 1, Hamilton Rating Scale for Depression (HAMD) item 3, and (MADRS) item 10. Dissociative and psychotomimetic symptoms were evaluated based on the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS)-four items. RESULTS: Multi-Ketamine infusions resulted in a lower (trend) antidepressant response (37.1 % versus 57.8 %) and antidepressant remission (15.8 % versus 47.4 %) in elderly patients with depression compared with younger patients with depression (all ps > 0.05). Interestingly, elderly patients with depression had a higher MADRS score after six ketamine infusions compared with younger patients (p = 0.04). No significant differences in SSI-part 1 scores, HAMD item 3 scores, MADRS item 10 scores, CADSS scores, and BPRS-four items scores were found between the two groups at any assessment point (all ps > 0.05). CONCLUSION: Our study shows that repeated-dose infusions of ketamine may be a feasible treatment strategy in elderly Chinese patients with depression; however, elderly patients with depression may be less responsive to ketamine compared with younger adults with depression.

A single-arm phase II clinical trial of anlotinib combined with chemotherapy for the treatment of metastatic triple-negative breast cancer.

Background: Anlotinib is a novel oral small-molecule tyrosine kinase inhibitor (TKI), which can inhibit angiogenesis. The purpose of this study was to evaluate the efficacy and safety of anlotinib combined with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC). Methods: This phase II clinical trial included 40 patients with metastatic TNBC who had previously received anthracycline and/or taxane treatment. All patients received anlotinib combined with chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and safety. Results: During May 1, 2019 and April 30, 2022, there were 40 patients enrolled in this study. The median PFS and median OS were 8.8 months (95% confidence interval [CI] 6.5-11.1 months) and 19.0 months (95% CI, 12.1-25.9 months), respectively. The ORR, CBR and DCR were 40.0% (16/40), 85.0% (34/40) and 95.0% (38/40), respectively. Cox univariate and multivariate analyses demonstrated that having more than 3 metastatic sites (p = 0.001; p = 0.020) was an independent and meaningful unfavorable prognostic factor for PFS. 37.5% of patients had grade 3 to 4 treatment-related adverse events (TRAEs). The grade 3 to 4 TRAEs included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%) and thrombocytopenia (2.5%). None of the patients withdrew from the study or died due to TRAEs. Conclusion: In this single-arm study, the treatment of metastatic TNBC with anlotinib combined with chemotherapy showed certain efficacy, and its toxicity was acceptable.

Association of anhedonia and suicidal ideation in patients with treatment-refractory depression after intravenous ketamine infusions.

OBJECTIVES: Accumulating evidence suggests that the effects of ketamine administered intravenously at subanaesthetic doses on both anhedonic symptoms and suicidal ideation occur independently of depressive symptoms in major depressive disorder (MDD) and bipolar disorder (BD). This study sought to determine the relationship between anhedonia and suicidal ideation after serial ketamine infusions. METHODS: A total of 79 subjects with either treatment-refractory MDD (n = 60) or BD (n = 19) were included in a clinical ketamine study. The Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia factor and the first five items of the Scale for Suicidal Ideations (SSI-Part I) were used to assess anhedonia symptoms and suicidal ideation, respectively. RESULTS: At baseline, anhedonia, as measured by the MADRS, was not significantly associated with suicidal ideation or specific suicide-related ideation as measured by SSI-Part I (all p's > 0.05). Only the 'wish to die' and 'desire to make a suicide attempt' items were positively associated with anhedonia at two weeks after the sixth ketamine infusion, which was independent of the reductions in depressive symptoms (all p's < 0.05). CONCLUSION: Anhedonia as measured by the MADRS appeared to not be positively related to suicidal ideation after serial ketamine infusions.KEY POINTSSerial ketamine (0.5 mg/kg) infusions have shown quick and dramatic antisuicidal and antianhedonic effects in patients with depression.The association between anhedonia and suicidal ideation after serial ketamine infusions is unclear.Anhedonia appeared to not be positively related to suicidal ideation after serial ketamine infusions.

Pyrotinib combined with trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer: a single-arm exploratory phase II trial.

PURPOSE: A substantial need for effective and safe treatment options is still unmet for patients with heavily pre-treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Herein, we assessed the efficacy and safety of pyrotinib plus trastuzumab and chemotherapy in patients with heavily treated HER2-positive MBC. METHODS: In this single-arm exploratory phase II trial, patients with HER2-positive MBC previously treated with trastuzumab plus lapatinib or pertuzumab, received pyrotinib plus trastuzumab and chemotherapy. The primary end point was progression-free survival (PFS) in the total population (TP). Secondary end points included PFS in the subgroup with brain metastases (Sub-BrM), confirmed objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), exploration of predictive factors of PFS, and safety. RESULTS: Between November 1, 2018, and March 31, 2021, 40 patients were eligible for this study. The median PFS reached 7.5 months (95% confidence interval [CI] 4.7 to 9.9 months) and 9.4 months (95% CI 6.6 to 12.1 months) in the TP and Sub-BrM, respectively. ORR was 50.5% (20/40). CBR was 75.5% (30/40) and DCR reached 97.5% (39/40). Cox univariate and multivariate analyses demonstrated that liver or/and lung metastases was the significant adverse prognostic factor for PFS (p = 0.018; p = 0.026; respectively). The most frequent grade 3 or 4 treatment-related adverse events were diarrhea, neutropenia and leukopenia. No new safety signals were observed. CONCLUSION: Pyrotinib plus trastuzumab and chemotherapy offered a promising option with manageable safety profile for heavily pre-treated HER2-positive MBC, especially for those without liver or/and lung metastases.

Acute-on-chronic liver failure following eribulin treatment for metastatic breast cancer: a case report.

The efficacy and tolerability of eribulin mesylate, a synthetic halichondrin B analog, in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes have been established. Acute-on-chronic liver failure (ACLF) is a clinical syndrome manifesting as acute and severe hepatic derangement resulting from varied insults in patients with established chronic liver disease or cirrhosis who did not previously receive eribulin. A middle-aged woman diagnosed with MBC and diffuse liver metastases who was pretreated with multi-line chemotherapy received eribulin as eighth-line chemotherapy and presented with hepatic encephalopathy, rapid bilirubin elevation, and significant coagulation dysfunction on day 4 in cycle 1. The patient was diagnosed with ACLF induced by eribulin. Therefore, ACLF may be a lethal and rare adverse event when patients with chronic liver metastases receive eribulin treatment, and clinicians' awareness should be increased for optimal prevention and prompt diagnosis and treatment.

Plasma VEGF Concentrations and Ketamine's Effects on Suicidal Ideation in Depression With Suicidal Ideation.

Objectives: Accumulating evidence supports a role for vascular endothelial growth factor (VEGF) in the pathogenesis of depression, but its relationship with the antisuicidal effects of ketamine is not clear. Our objective was to determine whether there was an association between the plasma VEGF (pVEGF) concentrations and the antisuicidal response to serial ketamine infusions. Methods: Six ketamine infusions (0.5 mg/kg) over a 12-day period were administered to sixty depressed individuals suffering from suicidal ideation. The Hamilton Depression Rating Scale (HAMD) suicide item, the Montgomery-Åsberg Depression Rating Scale (MADRS) suicide item, and the Beck Scale for Suicide Ideation (SSI-part I) were used to assess suicidal ideation at baseline, 1 day after the first infusion (day 1), 1 day following the last infusion (day 13), and again 2 weeks post-infusion (day 26). For this purpose, plasma was obtained at baseline, day 13 and 26. Results: The rates of antisuicidal response to ketamine were 61.7% (37/60), 81.7% (49/60), and 73.3% (44/60) at days 1, 13, and 26, respectively. The linear mixed model revealed significant time effects on suicidal ideation and pVEGF concentrations over time (all Ps < 0.05). Antisuicidal responders did not have significantly altered pVEGF concentrations compared with non-responders on day 13 and day 26 (all Ps > 0.05). No significant correlation was found between the baseline pVEGF concentration and suicidal ideation as measured by the SSI part 1, HAMD suicide item and MADRS suicide item on days 1, 13, and 26 (all ps > 0.05). Conclusion: This preliminary finding does not support a role for VEGF in the antisuicidal effects of serial ketamine treatments in individuals with depression and suicidal ideation. Further research is needed to confirm and expand these findings.

Comparative effectiveness of repeated ketamine infusions in treating anhedonia in bipolar and unipolar depression.

OBJECTIVES: Anhedonia is a common, persistent, and disabling phenomenon in patients with major depressive disorder (MDD) and bipolar depression (BD). This study was conducted to investigate the comparative effectiveness of repeated ketamine infusions in treating anhedonia in Chinese individuals suffering from MDD and BD. METHODS: Ninety-seven individuals suffering from MDD (n = 77) or BD (n = 20) were treated with six intravenous infusions of ketamine (0.5 mg/kg) administered over 40 min. Anhedonia was measured through the Montgomery-Åsberg Depression Rating Scale (MADRS). The antianhedonic response and remission were defined as ≥ 50% and ≥ 75% reduction in MADRS anhedonia subscale score one day after the sixth infusion, respectively. RESULTS: Anti-anhedonic response and remission rates after the sixth ketamine infusion were 48.5% (95% confidence interval =  38.3%-58.6%) and 30.9% (95% confidence interval = 21.6%-40.3%), respectively. When compared to baseline, a significant reduction in the MADRS anhedonia subscale score was observed at 4 h after the first infusion and was maintained with repeated infusions at any time point (all Ps < 0.05). The anti-anhedonic effect of ketamine did not differ between the MDD and BD groups. CONCLUSION: This preliminary study found that repeated ketamine infusions appeared to be effective at rapidly ameliorating anhedonia, with similar efficacy in MDD and BD.

Association of VEGF With Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Treatment-Refractory Depression.

Objectives: To first explore the role of plasma vascular endothelial growth factor (VEGF) concentrations in ketamine's antianhedonic effects, focusing on Chinese patients with treatment-refractory depression (TRD). Methods: Seventy-eight patients with treatment-refractory major depressive disorder (MDD) or bipolar disorder (BD) were treated with six ketamine infusions (0.5 mg/kg). Levels of anhedonia were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia item at baseline, day 13 and 26. Plasma VEGF concentrations were examined at the same time points as the MADRS. Results: Despite a significant reduction in anhedonia symptoms in individuals with treatment-refractory MDD (n = 59) or BD (n = 19) after they received repeated-dose ketamine infusions (p < 0.05), no significant changes in plasma VEGF concentrations were found at day 13 when compared to baseline (p > 0.05). The alteration of plasma VEGF concentrations did not differ between antianhedonic responders and non-responders at days 13 and 26 (all ps > 0.05). Additionally, no significant correlations were observed between the antianhedonic response to ketamine and plasma VEGF concentrations (all ps > 0.05). Conclusion: This preliminary study suggests that the antianhedonic effects of ketamine are not mediated by VEGF.

Association of plasma VEGF levels and the antidepressant effects of ketamine in patients with depression.

AIMS: Growing evidence suggests that vascular endothelial growth factor (VEGF) may be involved in the neuronal mechanisms underlying both depression aetiology and the response to ketamine treatments. The aim of this study was to examine whether changes in plasma VEGF levels are associated with the antidepressant effects of repeated ketamine infusions in patients with depression. METHODS: Ninety-six patients with depression were enrolled and received six ketamine infusions during a 12-day period. Depressive symptom severity and plasma VEGF levels were measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and an enzyme-linked immunosorbent assay (ELISA) respectively, at baseline, 13 days and 26 days. RESULTS: Despite a significant improvement in MADRS scores after patients received six ketamine infusions (p < 0.001), no changes in plasma VEGF levels were observed at 13 days when compared with baseline. Moreover, no significant difference in plasma VEGF levels at baseline and 13 days was found between ketamine responders and nonresponders. No association was found between the antidepressant effects of repeated ketamine treatments and plasma VEGF levels. CONCLUSION: This study indicated that VEGF may not be a potential predictor of antidepressant response to repeated intravenous administration of ketamine in patients with depression.

Plasma BDNF concentrations and the antidepressant effects of six ketamine infusions in unipolar and bipolar depression.

OBJECTIVES: Accumulating evidence has implicated that brain derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of depression, but its correlation with ketamine's antidepressant efficacy focusing on Chinese individuals with depression is not known. This study was aim to determine the correlation of plasma BDNF (pBDNF) concentrations and ketamine's antidepressant efficacy. METHODS: Ninety-four individuals with depression received six intravenous infusions ketamine (0.5 mg/kg). Remission and response were defined as Montgomery-Asberg Depression Rating Scale (MADRS) scores less than 10 and a reduction of 50% or more in MADRS scores, respectively. Plasma was collected at baseline and at 24 h and 2 weeks after completing six ketamine infusions (baseline, 13 d and 26 d). RESULTS: A significant improvement in MADRS scores and pBDNF concentrations was found after completing six ketamine infusions compared to baseline (all ps < 0.05). Higher baseline pBDNF concentrations were found in ketamine responders/remitters (11.0 ± 6.2/10.1 ± 5.8 ng/ml) than nonresponders/nonremitters (8.0 ± 5.5/9.2 ± 6.4 ng/ml) (all ps < 0.05). Baseline pBDNF concentrations were correlated with MADRS scores at 13 d (t =  - 2.011, p = 0.047) or 26 d (t =  - 2.398, p = 0.019) in depressed patients (all ps < 0.05). Subgroup analyses found similar results in individuals suffering from treatment refractory depression. CONCLUSION: This preliminary study suggests that baseline pBDNF concentrations appeared to be correlated with ketamine's antidepressant efficacy in Chinese patients with depression.

Cardiovascular effects of repeated subanaesthetic ketamine infusion in depression.

BACKGROUND: Ketamine produces significant rapid-onset and robust antidepressant effects in patients with major depressive disorder. However, this drug also has transient cardiovascular stimulatory effects, and there are limited data about potential predictors of these cardiovascular effects. METHODS: A total of 135 patients with unipolar and bipolar depression received a total of 741 ketamine infusions (0.5 mg/kg over 40 min). Blood pressure and pulse were monitored every 10 min during the infusions and 30 min after the infusions. Depressive, psychotomimetic and dissociative symptom severity was assessed at baseline and 4 hours after each infusion. RESULTS: The maximum blood pressure and pulse values were observed at 30-40 min during infusions. The largest mean systolic/diastolic blood pressure increases were 7.4/6.0 mmHg, and the largest mean pulse increase was 1.9 beats per min. No significant change in blood pressure and pulse was found in the second to sixth infusions compared with the first infusion. Patients who were older (age⩾50 years), hypertensive and receiving infusions while exhibiting dissociative symptoms showed greater maximal changes in systolic and diastolic blood pressure than patients who were younger (age<50 years), normotensive and without dissociative symptoms (all p < 0.05). Hypertensive patients had less elevation of pulse than normotensive patients (p < 0.05). Ketamine dosage was positively correlated with changes in systolic and diastolic blood pressure (all p < 0.05). CONCLUSIONS: Blood pressure and pulse elevations following subanaesthetic ketamine infusions are transient and do not cause serious cardiovascular events. Older age, hypertension, large ketamine dosage and dissociative symptoms may predict increased ketamine-induced cardiovascular effects.

Association between plasma levels of BDNF and the antisuicidal effects of repeated ketamine infusions in depression with suicidal ideation.

BACKGROUND: This study is the first to examine the association between plasma levels of brain-derived neurotrophic factor (BDNF) and the antisuicidal effects of repeated ketamine infusions in depressed patients with suicidal ideation. METHODS: Fifty-seven depressed patients with suicidal ideation received six ketamine infusions (0.5 mg/kg) during a 12 days period. Suicidality was measured with the Scale for Suicidal Ideations (SSI-part 1), item 10 of the Montgomery-Åsberg Depression Rating Scale (MADRS), and item 3 of the Hamilton Depression Rating Scale (HAMD) at baseline, 1 day after the first infusion (1 day), 1 day after the sixth infusion (13 days), and at 2 weeks after the last infusion (26 days). Plasma levels of BDNF were measured by enzyme-linked immunosorbent assay at baseline, 13 days, and 26 days. RESULTS: Overall, 46 (80.7%) depressed patients with suicidal ideation had an antisuicidal response at 13 days. Despite a significant reduction in suicidal symptoms over time, no changes in plasma levels of BDNF were found after ketamine treatment when compared with baseline. Correlation analysis showed that no significant association was observed between the plasma levels of BDNF and the changes in the severity of suicidal symptoms as measured by SSI-part 1, item 10 of the MADRS, or item 3 of the HAMD at 1 day, 13 days, and 26 days (all p < 0.05). CONCLUSION: Our results indicated that plasma levels of BDNF may not serve as a biomarker for determining the antisuicidal effects of six ketamine infusions in depressed patients with suicidal ideation.

Neurocognitive effects of six ketamine infusions and the association with antidepressant effects in treatment-resistant bipolar depression: a preliminary study.

OBJECTIVE: The N-methyl-D-aspartate subtype glutamate receptor antagonist ketamine has rapid antidepressant and antisuicidal effects in treating treatment-resistant bipolar depression (TRBD). The neurocognitive effects of repeated ketamine infusions in TRBD are not known. METHODS: Six intravenous infusions of ketamine (0.5 mg/kg over 40 min) were administered on a Monday-Wednesday-Friday schedule during a 12-day period on 16 patients with TRBD followed by a 2-week observational period. The assessment of neurocognitive function was conducted using the MATRICS Consensus Cognitive Battery at baseline, 13 and 26 days. Tasks were designed to test speed of processing, working memory, visual learning and verbal learning. RESULTS: A significant improvement was found only in scores of speed of processing (F = 9.9, p = 0.001) after a 2-week observational period, which was accounted for by the improvement of depression symptoms. There were no significant changes over time in terms of working memory, visual learning and verbal learning. Pearson correlation analysis showed that the improvement of depression symptoms through six ketamine infusions was greater among TRBD patients with lower working memory at baseline (r = 0.54, p = 0.03). In multiple regression analysis, the significant correlation was still maintained (beta = 0.67, t = 2.2, p = 0.04). CONCLUSION: This preliminary study indicated that six ketamine infusions were not harmful but were slightly beneficial for speed of processing in TRBD. However, this change was mainly accounted for the improvement of depression symptoms over time. Lower baseline working memory appears to be associated with greater antidepressant response after completion of six ketamine infusions in patients with TRBD.

Relationship between hippocampal volume and inflammatory markers following six infusions of ketamine in major depressive disorder.

BACKGROUND: Evidences suggest that inflammatory marker-mediated neuroplasticity contributes critically to brain changes following antidepressant treatment. To date, no study has examined the relationship between changes in hippocampal volume, depressive symptoms, and inflammatory markers following repeated ketamine treatment. METHODS: Forty-four patients with major depressive disorder received six intravenous ketamine (0.5 mg/kg) infusions over 12 days. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depressive symptoms, and peripheral blood was collected to test multiple cytokines and tryptophan (TRP) metabolites at baseline, 24 h and 14 days after the sixth infusion (day 13 and day 26). Magnetic resonance imaging (MRI) scans were carried out at baseline and day13, and FreeSurfer software was used to process the T1 images and analyze hippocampal volume. RESULTS: Following ketamine, a significant improvement in depressive symptoms, a small increase in right hippocampal volume and alterations in inflammatory markers was found. No significant association was found between changes in inflammatory markers and changes in hippocampal volume from baseline to day 13 (P>0.05), while a weak association was found between TRP metabolite changes and other cytokine changes from baseline to day 26 (beta=-0.357, t=-2.600, P = 0.013). LIMITATIONS: The patients continued receiving previous medications during ketamine treatment, which may have impacted hippocampal volume and inflammatory markers. CONCLUSIONS: Hippocampal volume increase following ketamine was an independent neurobiological effect that was not associated with changes in peripheral inflammatory markers, suggesting a likely complex neurobiological mechanism of the antidepressant effect of ketamine.

Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis.

Abnormal subcortical structures have been associated with major depressive disorder (MDD) and could be reversed by antidepressant treatment. To date no study has examined the relationship between subcortical volumes and repeated ketamine treatment. The current study investigated volume changes in specific subcortical structures and hippocampal subfields after six ketamine infusions. Forty-four patients with MDD received six subanesthetic dose infusions of ketamine. Depressive symptoms were assessed and magnetic resonance imaging scans were performed before and after six ketamine infusions. FreeSurfer software was used to process the T1 images and analyze the volumes of the subcortical regions and hippocampal subfields. After six ketamine infusions, increases were observed in the volumes of the left amygdala; the right hippocampus; the cornu ammonis 4 body, granule cell and molecular layer of the dentate gyrus body in the left hippocampus; and the cornu ammonis 4 head and molecular layer head in the right hippocampus. Positive correlations were found between symptom improvement and the pretreatment volumes of the right thalamus (r = 0.501; P = 0.001) and left subiculum head of the hippocampus (r = 0.471; P = 0.002), and changes in the volumes of the left amygdala (r = -0.452; P = 0.003) and the left cornu ammonis 4 body (r = -0.537; P < 0.001). Our findings provided evidence for critical roles of the amygdala and specific hippocampal subfields in the antidepressant effect of repeated ketamine treatment. Relatively larger volumes in right thalamus and left subiculum head in the hippocampus can predict a superior clinical outcome of ketamine treatment in MDD patients.

A preliminary study of adjunctive ketamine for treatment-resistant bipolar depression.

OBJECTIVES: Ketamine has shown rapid antidepressant effects in depressed patients. However, the antidepressant and antisuicidal effects of repeated ketamine infusions in patients with treatment-resistant bipolar depression (TRBD) are not known. METHODS: TRBD patients received six intravenous infusions of 0.5 mg/kg ketamine over 40 min on a Monday-Wednesday-Friday schedule during a 12-day period followed by a 2-week follow-up period. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and at each follow-up visit. RESULTS: Nineteen patients with TRBD were enrolled in the study, and 16 patients (84.2%) received all six ketamine infusions. After the first infusion, the rates of response and remission were 21.1% (95% CI: 0.9 to 21.2) and 15.8% (95% CI: 0 to 33.9), respectively, and after the sixth infusion, the rates of response and remission were 73.7% (95% CI: 51.9 to 95.5) and 63.2% (95% CI: 39.3 to 87.0), respectively. The average times for nineteen patients who responded and remitted were 9.1 and 12.5 days, respectively. There were large decreases in the scores on the MADRS and the Scale for Suicidal Ideation-part 1 within 4 h after the first infusion, and the decreases were maintained across subsequent infusions. There were no significant increases in dissociative and psychotomimetic symptoms as measured by the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS)-4 items, respectively. CONCLUSION: These pilot findings suggest the feasibility of repeated ketamine infusions at subanaesthetic doses for patients with TRBD. Future controlled studies are needed to confirm and expand these findings.

[Application of superb microvascular imaging in manifesting the blood flow of the penile cavernous artery in vascular ED patients].

OBJECTIVE: To investigate the application value of superb microvascular imaging (SMI) in the diagnosis of penile vascular ED. METHODS: Seventy-two ED patients underwent SMI and color Doppler flow imaging (CDFI), all ultrasonographically diagnosed with penile vascular ED. We compared SMI and CDFI in detecting the grades of blood flow in the cavernous artery and the lengths of time needed to obtain satisfactory blood flow spectrum from the patients. RESULTS: SMI mainly revealed grades Ⅲ and Ⅳ blood flow, in 43 and 20 of the 72 patients (87.5%), while CDFI chiefly manifested grades Ⅰ and Ⅱ blood flow, in 26 and 32 cases respectively (80.6%). The former showed significantly better manifestations of the penile cavernous artery than the latter. It took less time to obtain the spectrums of grades Ⅲ and Ⅳ blood flow (ï¼»1.52 ± 0.18ï¼½ and ï¼»1.21 ± 0.11ï¼½ min) than grades Ⅰ and Ⅱ (ï¼»5.23 ± 0.44ï¼½ and ï¼»4.46 ± 0.65ï¼½ min), and SIM took significantly less time than CDFI (ï¼»1.32 ± 0.42ï¼½ vs ï¼»4.53 ± 0.67ï¼½ min, P < 0.05). CONCLUSIONS: SMI is superior to CDFI in better manifesting the blood flow of the penile cavernous artery and shortening the examination time, and therefore deserves a wide application in the diagnosis of vascular ED.