Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.

Prospects for the Protective Mechanisms and Compounds of Bufei Huoxue Capsule against COVID-19 Convalescence: Evaluation of Integrating UHPLC-HRMS Analysis and Network Pharmacology Strategy.

INTRODUCTION: Most COVID-19 survivors are troubled with chronic persistent symptoms, which have currently no definitive treatments. Bufei Huoxue (BFHX) capsule exerts clinical benefit, while the material basis and molecular mechanism remain unclear. AIM: The study aimed to elucidate the protective mechanisms of BFHX capsules against COVID-19 convalescence. UHPLC-HRMS and various databases were employed to explore potential compounds and targets. PPI, MCODE, transcription factor (TF), and miRNA analyses were conducted to receive hub targets and corresponding upstream regulators. METHOD: Molecular docking was applied to verify the binding activity of compound and target. Further, GO, KEGG, WIKI, and Reactome analyses were performed, and compound-targetsymptom and gene-disease networks were constructed. A total of 127 compounds and 313 targets were acquired. A sum of 10 hub targets were screened and showed good binding affinities with critical compounds. RESULT: MLLT1, CBFB, and EZH2 were identified as key TFs, and hsa-mir-146a-5p, hsa-mir- 26b-5p, and hsa-mir-24-3p were predicted to be important miRNAs. BFHX capsule may alleviate the symptoms by targeting TNF, IL-6, IFNG, and TGF-ß1. Besides, BFHX capsule may exert a therapeutic effect on respiratory disease (especially pulmonary fibrosis and lung infection) and multi-system damage during COVID-19 convalescence by regulating cytokine-cytokine receptor interaction, as well as TGF-ß, TNF, and Toll-like receptor signaling pathways. CONCLUSION: In summary, BFHX capsule may exert a therapeutic effect on multi-system damages during COVID-19 convalescence through multiple compounds (such as albiflorin, isopsoralen, and neobavaisoflavone), multiple targets (such as TNF, IL-6, and EGF) and multiple pathways (TGF-ß, TNF, and Toll-like receptor signaling pathways).

The Chinese medicine Xin-tong-tai granule protects atherosclerosis by regulating oxidative stress through NOX/ROS/NF-κB signal pathway.

BACKGROUND: Xin-tong-tai Granule (XTTG), a traditional Chinese medicine, has been used to treat atherosclerosis (AS), but its mechanism is poorly understood. Intriguingly, oxidative stress has been recognized as vital factors in the treatment of atherosclerosis. PURPOSE: This study aims to explore the potential mechanism of XTTG for treating AS. METHODS: An in-vivo model of AS was established by feeding ApoE-/- mice with a high-fat diet (HFD), and the Human Aortic Vascular Smooth Muscle Cells (HAVSMCs) were induced by oxidized low-density lipoprotein (ox-LDL) in vitro. After treatment, the blood lipid levels and pathological aortic changes of each group were observed, and the cell proliferation and lipid droplet aggregation in each group were evaluated. The oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) levels and related NOX/ROS/NF-κB signaling pathway indicators were observed. RESULTS: XTTG improved blood lipid levels and pathological aortic changes of ApoE-/- mice with HFD feeding, inhibited HAVSMCs proliferation and lipid droplet aggregation induced by ox-LDL, reduced MDA content, increased SOD content, inhibited NOX4 and p22phox protein expression, downregulated ROS content, inhibited IKK-α, IKK-ß, NF-κB protein and mRNA expression and the phosphorylation of NF-κB. CONCLUSION: XTTG can inhibit NOX/ROS/NF-κB signaling pathway, reduce damages caused by oxidative stress, and exert anti-AS effects.

Cervical sagittal alignment changes following anterior cervical discectomy and fusion, laminectomy with fusion, and laminoplasty for multisegmental cervical spondylotic myelopathy.

OBJECTIVE: Cervical sagittal alignment changes (CSACs) influence outcomes and health-related quality-of-life. Anterior cervical discectomy and fusion (ACDF), laminectomy with fusion (LCF), and laminoplasty (LP) are common treatments for multisegmental cervical spondylotic myelopathy; however, these approaches need to be compared. METHODS: Our study included 167 patients who underwent ACDF, LCF, or LP. Patients were divided into four groups according to C2-C7 Cobb angle (CL): kyphosis (CL < 0°), straight (0° ≤ CL < 10°), lordosis (10° ≤ CL < 20°), and extreme lordosis (20° ≤ CL) groups. CSACs consist of two parts. CSAC from the preoperative period to the postoperative period is surgical correction change (SCC). CSAC from the postoperative period to the final follow-up period is postoperative lordosis preserving (PLP). Outcomes were evaluated using the Japanese Orthopaedic Association score and the neck disability index. RESULTS: ACDF, LCF, and LP had equivalent outcomes. ACDF had greater SCC than LCF and LP. During follow-up, lordosis decreased in the ACDF and LCF groups but increased in the LP group. For straight alignment, ACDF had greater CSAC and greater SCC than the LCF and LP groups but similar PLP. For lordosis alignment, ACDF and LP had positive PLP, and LCF had negative PLP. For extreme lordosis, ACDF, LP, and LCF had negative PLP; however, cervical lordosis in the LP group was relatively stable during follow-up. CONCLUSIONS: ACDF, LCF, and LP have different CSAC, SCC, and PLP according to a four-type cervical sagittal alignment classification. Preoperative cervical alignment is an important consideration in deciding the type of surgical treatment in CSM.

Compensatory classification in spine sagittal malalignment with lumbar degeneration.

OBJECTIVE: To generate a compensatory classification to evaluate sagittal spinal malalignment with lumbar degeneration. METHODS: We included 162 patients with low back pain who underwent full-length spinal radiography in our hospital from August 2019 to October 2021. Using full-length spine X-rays, we measured pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), C7 slope (C7S), thoracolumbar kyphosis (TLK), and C7 sagittal vertical axis (SVA). We also recorded the Oswestry Disability Index (ODI) and visual analog scale (VAS). Patients were divided into four groups based on the SRS-Schwab classification and four other groups based on the compensatory classification. RESULTS: ODI correlated with age, SS, LL, TK, C7-SVA, SRS-Schwab classification, and compensatory classification. Lumbar VAS score correlated with LL, TK, C7-SVA, SRS-Schwab classification, and compensatory classification. Leg VAS score only correlated with LL. Hidden imbalance and imbalance with compensation had more significant PT and larger TK than balance patients. The symptoms of the four compensatory classification groups gradually worsened. CONCLUSION: The spinal-pelvic sagittal balance in patients with lumbar degeneration based on pelvic and thoracic compensation can reflect spinal balance and symptoms. This parameter might help evaluate spine sagittal alignment in elderly patients with lumbar degeneration.

The ratio of cervical lordosis to C7 slope represents the reciprocal change between cervical sagittal alignment and global spinal alignment.

PURPOSE: This retrospective cross-sectional study investigated variations in the ratio of cervical lordosis to C7 slope (CL/C7S) at different stages of global sagittal balance to better understand how global sagittal alignment affects cervical alignment. METHODS: A total of 255 patients with the degenerative lumbar disease were retrospectively studied within a single medical center. Whole spine radiographs were used to evaluate sagittal parameters, mainly including occiput-C2 lordosis (OC2), cervical lordosis (CL), C7 slope (C7S), the ratio of cervical lordosis to C7 slope (CL/C7S), cervical sagittal vertical axis (CSVA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), PI minus LL mismatch (PI-LL), and sagittal vertical axis (SVA). Patients were divided into the balance group (SVA < 50 mm, PI-LL ≤ 10°), hidden imbalance group (SVA < 50 mm, PI-LL > 10°), and imbalance group (SVA > 50 mm). RESULTS: Significant correlations were found between CL/C7S and OC2 (r = - 0.334), CSVA (r = - 0.504), PI-LL (r = 0.189), and SVA (r = 0.309). Multivariable linear regression analysis indicated that patients in the hidden imbalance group had lower CL/C7S than those in the balance group (B = - 0.234, P < 0.001), whereas the value of CL/C7S in patients with imbalanced sagittal alignment was higher than those with balanced alignment (B = 0.164, P = 0.011). The mean value of CL/C7S was 0.71, 0.51, and 0.97 in the balance, hidden imbalance, and imbalance groups, respectively. The global spine tended to tilt forward as the LL decreased, while TK, PT, PI-LL, and SVA increased (all, P < 0.001) from the balance stage to the imbalance stage. CONCLUSIONS: CL/C7S tended to be lower when the thoracic extension increased to maintain global sagittal balance at the hidden imbalance stage. Inversely, CL/C7S increased significantly when the global spine showed severe anterior malalignment.

Four types of global spine sagittal alignment and compensation mechanism in adult patients with lumbar degenerative disease.

BACKGROUND: The objective of this study was to describe and classify common variations and compensation mechanisms in the sagittal alignment of the spine with lumbar degenerative disease. METHODS: A total of 230 patients over 18 years old who underwent whole-spine X-rays to evaluate lower back pain were enrolled in this study. C7 slope, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), cervical lordosis (CL), thoracolumbar kyphosis (TLK), and sagittal vertical axis (SVA) were measured. Patients were divided into Group A (balance without compensation), B (balance with compensation), C (unbalance with compensation), and D (unbalance without compensation) according to spinopelvic balance and thoracic compensation. RESULTS: Group A had the largest LL, smallest PT, largest SS, and best clinical parameters of the four groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001). The age increased gradually from Group B to Group D. Group B had an increased TK compared with Group A (p < 0.001). Group C had an increased TK compared with Group A (p < 0.001). Group D had an increased C7 slope compared with Group A (p = 0.022). CONCLUSIONS: This classification is shown four different regional and global alignments of the spine. Compensation took place to keep the balance of the spine. Classification types were consistent with age, compensation abilities, and clinical parameters. This classification potentially represents a valuable tool for comprehensive analysis of lumbar degenerative before surgical treatment considering sagittal balance.

Changes in T1 slope and cervical sagittal vertical axis correlate to improved neurological function recovery after cervical laminoplasty.

Purpose: To investigate the influence of changes in T1 slope (T1S) and cervical sagittal vertical axis (CSVA) on cervical laminoplasty outcomes. Methods: Eighty-one patients with cervical spondylotic myelopathy (CSM) treated with cervical laminoplasty were enrolled in this study. Demographic parameters included age and follow-up time. Imaging data included occiput-C2 lordosis (OC2), C2-C7 Cobb angle (CL), T1S, CSVA. Outcome assessment indicators included the Japanese Orthopedic Association (JOA) score, JOA recovery rate, and neck disability index (NDI). All patients were grouped based on preoperative T1S and variation in CL after surgery, respectively. Patients with decreased CL postoperatively were further grouped according to whether they were combined with T1S reduction. Results: There were no significant differences in the final JOA score, JOA recovery rate, or NDI between patients with different T1S. Patients with loss of CL postoperatively had lower JOA score and JOA recovery rate, but higher NDI than patients with sustained CL. Furthermore, patients with CL loss but compensate for it with reduction in T1S had lower CSVA, higher JOA score and JOA recovery rate than those with CL loss alone. Conclusions: Decreased T1S postoperatively prevents the tendency of the cervical spine to tilt forward by regulating CSVA and facilitates recovery of neurological function after cervical laminoplasty.

The discrepancy between preoperative cervical sagittal vertical axis and T1 slope predisposes inferior clinical outcomes in patients with cervical spondylotic myelopathy after cervical laminoplasty.

Objective: Cervical sagittal parameters have been widely used to predict clinical outcomes in patients with cervical spondylotic myelopathy (CSM). This study aims to coin a novel cervical sagittal parameter defined as the ratio of cervical sagittal vertical axis to T1 slope (CSVA/T1S) and to investigate the correlation between CSVA/T1S and postoperative HRQOL after laminoplasty. Methods: A total of 102 CSM patients treated with cervical laminoplasty from our database were retrospectively reviewed. All patients were followed up for >12 months. Radiological parameters were measured using lateral cervical radiographs, including occiput-C2 lordosis (OC2), cervical lordosis (CL), CSVA, and T1S. Clinical parameters included the Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and JOA recovery rate. Patients were grouped by preoperative T1S, T1S-CL, and CSVA/T1S value, respectively. Clinical and radiological outcomes were compared between the groups. Results: Patients with high CSVA/T1S had greater OC2 and CSVA but lower CL than those in the low CSVA/T1S group pre-and postoperatively. With respect to HRQOL results, the final NDI was 12.46 ± 9.11% in the low CSVA/T1S group, which was significantly lower than that in the high CSVA/T1S group (17.68 ± 8.81%, P = 0.040). Moreover, only CSVA/T1S was detected to be significantly correlated with final NDI (r = 0.310, P = 0.027). No significant correlation was found between clinical results and other cervical sagittal parameters, including T1S, CSVA, and T1S-CL. Conclusions: Preoperative CSVA/T1S was correlated with postoperative NDI in patients with CSM after cervical laminoplasty. Patients with low preoperative CSVA/T1S achieved better neurological function improvement after cervical laminoplasty. Cervical laminoplasty could be an appropriate choice for patients with lower preoperative CSVA/T1S.

Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a major challenge threatening the global healthcare system. Respiratory virus infection is the most common cause of asthma attacks, and thus COVID-19 may contribute to an increase in asthma exacerbations. However, the mechanisms of COVID-19/asthma comorbidity remain unclear. METHODS: The "Limma" package or "DESeq2" package was used to screen differentially expressed genes (DEGs). Alveolar lavage fluid datasets of COVID-19 and asthma were obtained from the GEO and GSV database. A series of analyses of common host factors for COVID-19 and asthma were conducted, including PPI network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis and drug candidate prediction. Finally, the key host factors were verified in the GSE152418 and GSE164805 datasets. RESULTS: 192 overlapping host factors were obtained by analyzing the intersection of asthma and COVID-19. FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5 as host factors were tightly connected in the PPI network. Module analysis identified five modules with different biological functions and pathways. According to the degree values ranking in the PPI network, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were considered as the key cohost factors for COVID-19 and asthma. The H2O2, VEGF, IL-1 and Wnt signaling pathways had the strongest activities in the upstream pathways. Tissue-specific enrichment analysis revealed the different expression levels of the five critical host factors. LY294002, wortmannin, PD98059 and heparin might have great potential to evolve into therapeutic drugs for COVID-19 and asthma comorbidity. Finally, the validation dataset confirmed that the expression of five key host factors were statistically significant among COVID-19 groups with different severity and healthy control subjects. CONCLUSIONS: This study constructed a network of common host factors between asthma and COVID-19 and predicted several drugs with therapeutic potential. Therefore, this study is likely to provide a reference for the management and treatment for COVID-19/asthma comorbidity.

Morphological factors and cardiac doses in whole breast radiation for left-sided breast cancer.

BACKGROUND: To investigate the impact of the breast size, shape, maximum heart depth (MDH), and chest wall hypotenuse (the distance connecting middle point of the sternum and the length of lung draw on the selected transverse CT slice) on the volumetric dose to heart with whole breast irradiation (WBI) of left-sided breast cancer patients. MATERIALS AND METHODS: Fifty-three patients with left-sided breast cancer undergoing adjuvant intensity-modulated radiotherapy (IMRT) were enrolled in the study. The primary breast size and shape, MHD and DCWH (chest wall hypotenuse) were contoured on radiotherapy (RT) planning CT slices. The dose data of hearts were obtained from the dose-volume histograms (DVHs). Data were analyzed by one-way analysis of variance (ANOVA), Student's t-test and linear regression analysis. RESULTS: Breast size was independent of heart dose, whereas breast shape, MHD and DCWH were correlated with heart dose. The shapes of breasts were divided into four types, as the flap type, hemisphere type, cone type and pendulous type with heart mean dose being 491.8±234.6 cGy, 752.7±219.0 cGy, 620.2±275.7 cGy, and 666.1±238.0 cGy, respectively. The flap type of breasts shows a strong statistically reduction in heart dose, compared to others (p=0.008 for V30 of heart). DCWH and MHD were found to be the most important parameters correlating with heart dose in WBI. CONCLUSIONS: More attention should be paid to the heart dose of non-flap type patients. The MHD was found to be the most important parameter to correlate with heart dose in tangential WBI, closely followed by the DCWH, which could help radiation oncologists and physicsts evaluate heart dose and design RT plan in advance.

A comparison of the different 3D CT scanning modes on the GTV delineation for the solitary pulmonary lesion.

OBJECTIVES: To investigate the impacts of the different three-dimensional CT (3DCT) scanning modes on the GTV delineation for solitary pulmonary lesion (SPL) based on four-dimensional CT (4DCT), and to evaluate the feasibility of using the spiral CT scan in CT simulation. MATERIALS AND METHODS: Twenty-one patients with SPL underwent axial CT scan, spiral CT scan and 4DCT simulation scan during free-breathing, respectively. The same clinical radiation oncologist delineated the gross tumor volume (GTV) under the same CT window setting. GTVA and GTVS were created from the axial and spiral images, respectively. ITVMIP was created from the maximum intensity projection (MIP) reconstructed 4D images. The target volumes and position between GTVA, GTVS and ITVMIP were compared. The matching index (MI) between GTVA and GTVS, and the correlation between MI and GTVS were evaluated. RESULTS: ITVMIP was significantly larger than GTVA and GTVS (ps = 0.000). The ratios of ITVMIP to GTVA and GTVS were 1.57 ± 0.54 and 1.66 ± 0.61, respectively. There was no significant difference between GTVA and GTVS(p = 0.16). A comparison of the centroidal positions in x, y, and z directions for GTVA, GTVS and GTV4Dmip showed no significant difference (px = 0.17, py = 0.40, pz = 0.48). Additionally, there was no difference between distances from the centroidal positions of GTVA and GTVS to the origin of coordinates (p = 0.51). MI between GTVA and GTVS was 0.41 ± 0.24 (range 0-0.89), and it was positively correlated with the tumor volume (r = 0.64, p = 0.002). CONCLUSION: There was no impact on the volume or centroidal position of GTV by the axial scan or spiral scan in 3DCT simulation for SPL. MI between GTVA and GTVS was small. A positively correlation was found between MI and GTVS. Relative to axial scanning mode, spiral CT scan was more timesaving and more efficient, it was feasible in 3DCT simulation for SPL.