Association of anhedonia with brain-derived neurotrophic factor and interleukin-10 in major depressive disorder.

BACKGROUND: Anhedonia, a core symptom of major depressive disorder (MDD), manifests in two forms: anticipatory and consummatory, reflecting a diminished capacity to anticipate or enjoy pleasurable activities. Prior studies suggest that brain-derived neurotrophic factor (BDNF) and interleukin-10 (IL-10) may play key roles in the emergence of anhedonia in MDD. The specific relationships between these biomarkers and the two forms of anhedonia remain unclear. This study investigated the potential links between BDNF, IL-10, and both forms of anhedonia in MDD patients. METHODS: This study included 43 participants diagnosed with MDD and 58 healthy controls. It involved detailed assessments of depression and anxiety levels, anticipatory and consummatory pleasure, cognitive functions, and a broad spectrum of plasma biomarkers, such as C-reactive protein, various interleukins, and BDNF. Using partial correlation, variables related to pleasant experiences were identified. Stepwise multiple linear regression analysis was applied to pinpoint the independent predictors of anhedonia in the MDD group. RESULTS: Demographically, both groups were comparable in terms of age, sex, body mass index, educational year, and marital status. Individuals with MDD displayed markedly reduced levels of anticipatory and consummatory pleasure, higher anxiety, and depression scores compared to healthy controls. Additionally, cognitive performance was notably poorer in the MDD group. These patients also had lower plasma diamine oxidase levels. Analysis linked anhedonia to impaired delayed memory. Regression results identified IL-10 and BDNF as independent predictors of anticipatory and consummatory anhedonia, respectively. CONCLUSION: These findings demonstrate that anticipatory and consummatory anhedonia are influenced by independent factors, thereby providing critical insights into the distinct neuroimmunological mechanisms that underlie various forms of anhedonia. Clinicl Trial Registration Number: NCT03790085.

Circ_0020123, a New Circular RNA Biomarker for Deep Vein Thrombosis in Pregnant Women.

BACKGROUND: Deep vein thrombosis (DVT) commonly occurs among vascular diseases globally, for which circular RNAs (circRNAs) are becoming a promising option by mediating functions of human umbilical vein endothelial cells (HUVECs). Therefore, this study focuses on whether circ_0020123 plays a role in HUVECs. METHODS: Pregnant women with DVT (n = 39) and without DVT (n = 39) were selected as the observation group and control group, respectively. Circ_0020123 expression in serum of pregnant women with DVT was assessed by RT-qPCR. The risk factors of DVT in pregnant women were analyzed by single factor logistic regression. HUVECs were treated with oxidized low-density lipoprotein (ox-LDL) to construct an in vitro model. Cell proliferation, tube formation ability, migration, and apoptosis were determined by cell counting kit-8, tube formation assay, Transwell assay, and flow cytometry. The levels of oxidative stress, inflammatory factors, endothelin-1 (ET-1), and von Willebrand factor (VWF) in cell supernatant were detected. RESULTS: The mode of delivery (cesarean delivery), postpartum hemorrhage (yes), puerperal bedtime (> 72 hours), and increased circ_0020123 were independent risk factors for DVT in pregnant women. Knockdown of circ_0020123 promoted HUVEC proliferation and angiogenesis in vitro. CONCLUSIONS: Clinical analysis of risk factors for DVT in pregnant women and positive measures for prevention can effectively avoid the formation of DVT. Circ_0020123 is a new circRNA biomarker for DVT in pregnant women.

Robustness of VMAT to setup errors in postmastectomy radiotherapy of left-sided breast cancer: Impact of bolus thickness.

BACKGROUND: Volumetric modulated arc therapy (VMAT) with varied bolus thicknesses has been employed in postmastectomy radiotherapy (PMRT) of breast cancer to improve superficial target coverage. However, impact of bolus thickness on plan robustness remains unclear. METHODS: The study enrolled ten patients with left-sided breast cancer who received radiotherapy using VMAT with 5 mm and 10 mm bolus (VMAT-5B and VMAT-10B). Inter-fractional setup errors were simulated by introducing a 3 mm shift to isocenter of the original plans in the anterior-posterior, left-right, and inferior-superior directions. The plans (perturbed plans) were recalculated without changing other parameters. Dose volume histograms (DVH) were collected for plan evaluation. Absolute dose differences in DVH endpoints for the clinical target volume (CTV), heart, and left lung between the perturbed plans and the original ones were used for robustness analysis. RESULTS: VMAT-10B showed better target coverage, while VMAT-5B was superior in organs-at-risk (OARs) sparing. As expected, small setup errors of 3 mm could induce dose fluctuations in CTV and OARs. The differences in CTV were small in VMAT-5B, with a maximum difference of -1.05 Gy for the posterior shifts. For VMAT-10B, isocenter shifts in the posterior and right directions significantly decreased CTV coverage. The differences were -1.69 Gy, -1.48 Gy and -1.99 Gy, -1.69 Gy for ΔD95% and ΔD98%, respectively. Regarding the OARs, only isocenter shifts in the posterior, right, and inferior directions increased dose to the left lung and the heart. Differences in VMAT-10B were milder than those in VMAT-5B. Specifically, mean heart dose were increased by 0.42 Gy (range 0.10 ~ 0.95 Gy) and 0.20 Gy (range -0.11 ~ 0.72 Gy), and mean dose for the left lung were increased by 1.02 Gy (range 0.79 ~ 1.18 Gy) and 0.68 Gy (range 0.47 ~ 0.84 Gy) in VMAT-5B and VMAT-10B, respectively. High-dose volumes in the organs were increased by approximate 0 ~ 2 and 1 ~ 3 percentage points, respectively. Nevertheless, most of the dosimetric parameters in the perturbed plans were still clinically acceptable. CONCLUSIONS: VMAT-5B appears to be more robust to 3 mm setup errors than VMAT-10B. VMAT-5B also resulted in better OARs sparing with acceptable target coverage and dose homogeneity. Therefore 5 mm bolus is recommended for PMRT of left-sided breast cancer using VMAT.

A practical method to improve the performance of knowledge-based VMAT planning for endometrial and cervical cancer.

PURPOSE: The aim of this work was to demonstrate a practical and effective method to improve the performance of RapidPlan (RP) model. METHODS: 203 consecutive clinical VMAT plans (P0) for cervical and endometrial cancer were used to train an RP model (M0). The plans were then reoptimized by M0 to generate 203 new plans (P1). Compared with P0, 150 plans with a lower mean dose (MD) of bladder, rectum and PBM were selected from P1 to configure a new RP model (M1). A final RP model (M2) was trained using plans in M1 and the remaining 53 plans from P1 (excluding OARs with worse MD) and the corresponding plans from P0 (only including OARs with better MD). The models were validated on the mentioned 53 plans (closed-loop set) and 46 patient cohorts outside the training library (open-loop set). p < 0.05 was considered statistically significant. RESULTS: For closed-loop validation, the difference of D2%, D98% and CI95% between groups was of no statistical significance, the homogeneity index (HI) was lower in the groups of RP models (p < 0.05). The MD of all OARs decreased monotonically in the sequence of the clinical group, group M0, M1 and M2, except the MD of bowel in M1 and MD of LFH in M2. Similarly, for open-loop validation, there was no significant difference in D2%, D98% and HI between groups, but CI95% was larger in the clinical group (p < 0.05). The MD of all OARs decreased monotonically in the sequence of the clinical group, group M0, M1 and M2, with the exception of bowel in M1. CONCLUSION: The practical method of incorporating plan data of better-sparing OARs from both the clinical VMAT plans and the re-optimized plans could further improve the performance of the RP model.

Temporary pacemaker protected transjugular intrahepatic portosystemic shunt in a patient with acute variceal bleeding and bradyarrhythmia: A case report.

BACKGROUND: Esophagogastric varices are a common complication of cirrhosis with portal hypertension and endoscopic treatment has been recognized as a primary preventive and therapeutic option for such patients; however, it should be noted that bradyarrhythmia is regarded as one of the contraindications to endoscopic examination. Meanwhile, acute variceal bleeding may result in a high mortality rate in cirrhotic patients with portal hypertension accompanied by bradyarrhythmia. At present, there is an absence of reports concerning the treatment of such group of patients who underwent transjugular intrahepatic portosystemic shunt (TIPS). The present report details the case of a cirrhotic patient with acute variceal bleeding accompanied by bradyarrhythmia who underwent TIPS under temporary pacemaker protection. CASE SUMMARY: We report the case of a 64-year-old male patient who was confirmed with bradyarrhythmia by ambulatory electrocardiogram 24 h before the operation. The patient was successfully treated by TIPS under temporary pacemaker protection. CONCLUSION: In terms of cirrhotic patients with abnormal cardiac electrophysiological conduction, TIPS may be effective in reducing the complications of portal hypertension following the exclusion of severe pulmonary hypertension and heart failure, showing moderate feasibility in clinical applications.

Computed Tomography-Based Evaluation of Volume and Position Changes of the Target Region and Organs at Risk During Radiotherapy for Esophageal Cancer: A Pilot Study.

OBJECTIVE: To analyze changes in volume and position of target regions and organs at risk (OARs) during radiotherapy for esophageal cancer patients. METHODS: Overall, 16 esophageal cancer patients who underwent radiotherapy, including 10 cases of intensity-modulated radiation therapy (IMRT) and six of three-dimensional conformal radiotherapy (3D-CRT), were enrolled. The prescription doses for the planning target volumes (PTVs) were as follows: PTV1, 64 Gy/32 fractions; and PTV2, 46 Gy/23 fractions. Repeat computed tomography (CT) was performed for patients after the 5th, 10th, 15th, 20th, and 25th fractions. Delineation of the gross tumor volume (GTV) and OAR volume was determined using five repeat CTs performed by the same physician. The target and OAR volumes and centroid positions were recorded and used to analyze volume change ratio (VCR), center displacement (ΔD), and changes in the distance from the OAR centroid positions to the planned radiotherapy isocenter (distance to isocenter, DTI) during treatment. RESULTS: No patient showed significant changes in target volume (TV) after the first week of radiotherapy (five fractions). However, TV gradually decreased over the following weeks, with the rate slowing after the fourth week (40 Gy). The comparison of TV from baseline to 40 Gy (20 fractions) showed that average GTVs decreased from 130.7 ± 63.1 cc to 92.1 ± 47.2 cc, with a VCR of -29.21 ± 13.96% (p<0.01), while the clinical target volume (CTV1) decreased from 276.7 ± 98.2 cc to 246.7 ± 87.2 cc, with a VCR of -10.34 ± 7.58% (p<0.01). As TVs decreased, ΔD increased and DTI decreased. After the fourth week of radiotherapy (40 Gy), centroids of GTV, CTV1, and prophylactic CTV (CTV2) showed average deviations in ΔD of 7.6 ± 4.0, 6.9 ± 3.4, and 6.0 ± 3.0 mm, respectively. The average DTI of the heart decreased by 4.53 mm (from 15.61 ± 2.96 cm to 15.16 ± 2.27 cm). CONCLUSION: During radiotherapy for esophageal cancer, Targets and OARs change significantly in volume and position during the 2nd-4th weeks. Image-guidance and evaluation of dosimetric changes are recommended for these fractions of treatment to appropriate adjust treatment plans.

68Ga-fibroblast activation protein inhibitor PET/CT on gross tumour volume delineation for radiotherapy planning of oesophageal cancer.

BACKGROUND AND PURPOSE: To compare 68Ga-fibroblast activation protein inhibitor (FAPI) and 18F-FDG PET/CT in imaging locally advanced oesophageal cancer, and evaluate the potential usefulness of 68Ga-FAPI PET/CT on gross target volume (GTV) delineation aimed at radiotherapy planning for oesophageal cancer as compared with contrast-enhanced CT (CE-CT) and 18F-FDG PET/CT. MATERIALS AND METHODS: Twenty-one patients with newly diagnosed oesophageal cancer who underwent both 18F-FDG and 68Ga-FAPI PET/CT scans were selected. GTVs of the primary tumours based on CE-CT (GTVCT), PET/CT, and CE-CT plus PET/CT were delineated. Gross tumour lengths were measured by GTVs and endoscopy and recorded. RESULTS: The 68Ga-FAPI PET showed significantly higher radiotracer uptake than 18F-FDG PET (median SUVmax 16.71 vs. 11.23; P = 0.002) in the primary tumours. SUV thresholds of FAPI ×20%, 30%, 40%, and FDG ×40% showed similar lesion lengths compared with that in endoscopic examination (P > 0.05). GTVCT demonstrated the largest volume (median: 48.80 mm3, range: 14.83-162.23 mm3) than PET-based GTVs. For PET/CT-guided complementary contouring of GTVCT, four patients (19%) were increased by FAPI ×20% and 30%, two patients (9.5%) were increased by FAPI ×40%, and only one patient was increased by FDG ×40%. Furthermore, the volume of GTV based on CE-CT plus FAPI ×20%, 30%, and 40% showed no significant difference with GTVCT and planning target volume based CE-CT plus FAPI-PET and meets the organ at risk standard. CONCLUSION: The 68Ga-FAPI PET/CT methodology showed favourable tumour-to-background contrast in oesophageal cancer and might provide additional information for target volume delineation and help avoid tumour geographic misses.

Dosimetric superiority of IMRT with jaw tracking technique for whole esophagus and T-shaped field radiotherapy in advanced esophageal cancer.

PURPOSE: For whole esophagus and T-shaped field radiotherapy using intensity modulated radiotherapy (IMRT) technique in advanced esophageal cancer, lower absorbed doses to lung and heart remains a challenge. The aim of this study was to investigate the dosimetric superiority in IMRT plans with jaw tracking technique for whole esophagus radiotherapy. METHODS AND MATERIALS: Thirty-two patients with esophageal cancer were subjected to IMRT treatment plans using Eclipse treatment planning system. For every patient, four different plans were generated with six gantry angles: six large fields IMRT plans with fixed jaw (6F-IMRT), six large fields IMRT plans with jaw tracking technique (6F-IMRT-T), twelve small fields IMRT plans with fixed jaw (12F-IMRT), and twelve small fields IMRT plans with jaw tracking technique (12F-IMRT-T). Dosimetric evaluation was assessed for all plans. RESULTS: For every technique, there were no differences in planning target volume (PTV) coverage and conformity. 6F-IMRT-T plans could significantly reduce lung irradiation with 7.9% (P<0.001) reduction in V5lung and 2.5% (P<0.001) reduction in V20 lung respectively compared to 6F-IMRT plans. 12F-IMRT-T plans resulted in superior plans compared to 12-IMRT plans with a reduction of 2.9% (P<0.001) in V5lung and 0.9% (P<0.001) in V20 lung, respectively. For heart irradiation, 6F-IMRT-T and 12F-IMRT-T plans were slightly superior to 6F-IMRT and 12-IMRT plans respectively with a reduction of 1.1 Gy and 0.5 Gy in the respective mean doses. CONCLUSIONS: By the use of jaw tracking technique, the IMRT plans resulted in further lung and heart sparing compared to fixed jaw plans for radiotherapy in esophageal cancer.

Dosimetric superiority of flattening filter free beams for single-fraction stereotactic radiosurgery in single brain metastasis.

For single-fraction stereotactic radiosurgery (SRS) using linac in brain metastases, more accurate treatment delivery with higher tumor absorbed doses and lower absorbed doses to normal tissues remains an enormous challenge. The purpose of this study was to investigate the dosimetric superiority in flattening filter free beams (FFF) for volumetric modulated arc therapy (VMAT) in single brain metastasis. 68 patients with single brain metastasis were included in this study. Every patient was subjected to VMAT treatment plans using 6 MV standard flattened (FF) beams (VMAT_FF) and 6 MV FFF beams (VMAT_FFF) with single fraction doses of 20 Gy. Dosimetric evaluation was performed by analysis of target coverage, dose gradients, beam-on time (BOT), gantry speed and number of monitor units (MU). There were no differences between VMAT_FF and VMAT_FFF plans in conformity and MU. VMAT_FFF plans showed obvious superiority in homogeneity, dose gradients and efficiency. For the mean BOT, VMAT_FFF plans provided a significant decrease by 42.8% compared with VMAT_FF. By the use of FFF beams, brain irradiation was minimized with about 2% reductions in low-dose regions (about 5-10 Gy). FFF beams not only resulted in more efficiency by reducing treatment time, but also provided further brain sparing compared to traditional techniques for SRS in single brain metastasis.

Modified Volumetric Modulated Arc Therapy in Left Sided Breast Cancer After Radical Mastectomy With Flattening Filter Free Versus Flattened Beams.

Conventional volumetric modulated arc therapy (C-VMAT) for breast cancer after radical mastectomy had its limitation that resulted in larger volumes of normal tissue receiving low doses. We explored whether there was a way to deal with this disadvantage and determined the potential benefit of flattening filter-free (FFF) beams.Twenty patients with breast cancer after radical mastectomy were subjected to 3D conformal radiotherapy (3DCRT) and VMAT treatment planning. For VMAT plans, 3 different designs were employed with RapidArc form: conventional-VMAT plan (C-VMAT), modified-VMAT plan (M-VMAT), and modified-VMAT plan using FFF beams (M-VMAT-F). Plan quality and efficiency were assessed for all plans.For each technique in homogeneity, there were no statistically significant differences. VMAT plans showed superiority compared with 3DCRT in conformity. C-VMAT plans were obviously not only superior to 3DCRT in the medium to high-dose regions (about 15-50 Gy) but also resulted in larger volumes in low-dose regions (about 0-10 Gy). M-VMAT plans were similar to M-VMAT-F. Both of them might significantly reduce the regions of low dose compared with C-VMAT (V5lung: ∼ 11.5%; V5heart: ∼ 23.8%, P < 0.05), even less than 3DCRT in heart irradiation (V2.5heart, 9.4%, P < 0.05). For liver, contralateral breast, and lung irradiation, M-VMAT-F plans were slightly superior to M-VMAT with a reduction of ∼0.08, 0.2, and 0.24 Gy in the respective mean doses (P < 0.05).C-VMAT plans showed superiority compared with 3DCRT, while also resulted in larger volumes of normal tissue receiving low doses. M-VMAT and M-VMAT-F plans might not only reduce the region in the medium to high doses but also have lower volumes in low-dose regions. M-VMAT-F plans were slightly superior compared with M-VMAT due to further contralateral organs sparing.

The Effect of Flattening Filter Free on Three-dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), and Volumetric Modulated Arc Therapy (VMAT) Plans for Metastatic Brain Tumors from Non-small Cell Lung Cancer.

Flattening filter free (FFF) may affect outcome measures of radiotherapy. The objective of this study is to compare the dosimetric parameters in three types of radiotherapy plans, three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT), with or without the flattening filter (FF), developed for the treatment of metastatic brain tumors from non-small cell lung cancer (NSCLC). From July 2013 to October 2013, 3D-CRT, IMRT, and VMAT treatment plans were designed using 6 MV and 10 MV, with and without FF, for 10 patients with brain metastasis from NSCLC. The evaluation of the treatment plans included homogeneity index (HI), conformity index (CI), monitor units (MU), mean dose (Dmean), treatment time, and the influence of FFF on volumes. There was no difference in CI or HI between FFF and FF models with 3D-CRT, IMRT, and VMAT plans. At 6 MV, a lower Dmean was seen in the FFF model of 3D-CRT and in the VMAT plan at 10 MV. In the IMRT 6 MV, IMRT 10 MV, and VMAT 10 MV plans, higher MUs were seen in the FFF models. FFF treatments are similar in quality to FF plans, generally lead to more monitor units, and are associated with shorter treatment times. FFF plans ranked by the order of superiority in terms of a time advantage are VMAT, 3D-CRT, and IMRT.

Planning study of flattening filter free beams for volumetric modulated arc therapy in squamous cell carcinoma of the scalp.

PURPOSE: Flattening filter free (FFF) beams show the potential for a higher dose rate and lower peripheral dose. We investigated the planning study of FFF beams with their role for volumetric modulated arc therapy (VMAT) in squamous cell carcinoma of the scalp. METHODS AND MATERIALS: One patient with squamous cell carcinoma which had involvement of entire scalp was subjected to VMAT using TrueBeam linear accelerator. As it was a rare skin malignancy, CT data of 7 patients with brain tumors were also included in this study, and their entire scalps were outlined as target volumes. Three VMAT plans were employed with RapidArc form: two half-field full-arcs VMAT using 6 MV standard beams (HFF-VMAT-FF), eight half-field quarter-arcs VMAT using 6 MV standard beams (HFQ-VMAT-FF), and HFQ-VMAT using FFF beams (HFQ-VMAT-FFF). Prescribed dose was 25 × 2 Gy (50 Gy). Plan quality and efficiency were assessed for all plans. RESULTS: There were no statistically significant differences among the three VMAT plans in target volume coverage, conformity, and homogeneity. For HFQ-VMAT-FF plans, there was a significant decrease by 12.6% in the mean dose to the brain compared with HFF-VMAT-FF. By the use of FFF beams, the mean dose to brain in HFQ-VMAT-FFF plans was further decreased by 7.4% compared with HFQ-VMAT-FF. Beam delivery times were similar for each technique. CONCLUSIONS: The HFQ-VMAT-FF plans showed the superiority in dose distributions compared with HFF-VMAT-FF. HFQ-VMAT-FFF plans might provide further normal tissue sparing, particularly in the brain, showing their potential for radiation therapy in squamous cell carcinoma of the scalp.