ABSTRACT
Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum ß-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type â N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.
Subject(s)
Bone Density Conservation Agents , Bone Diseases , Denosumab , Hypocalcemia , Multiple Myeloma , Zoledronic Acid , Humans , Zoledronic Acid/administration & dosage , Denosumab/adverse effects , Denosumab/administration & dosage , Multiple Myeloma/drug therapy , Retrospective Studies , Bone Diseases/etiology , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/adverse effects , Hypocalcemia/chemically induced , Hypocalcemia/etiology , Male , Female , Treatment Outcome , Middle Aged , AgedSubject(s)
Myocarditis , Humans , Myocarditis/diagnostic imaging , Magnetic Resonance Imaging , Myocardium , Giant CellsABSTRACT
Objective: To explore the basic characteristics of conventional echocardiography of apical hypertrophic cardiomyopathy (ApHCM) patients complicating with left ventricular apical aneurysm (LVAA). Methods: This is a retrospective study. Patients who underwent echocardiography and cardiac magnetic resonance (CMR) and were diagnosed with ApHCM complicated with LVAA by CMR at Fuwai Hospital, Chinese Academy of Medical Sciences from August 2012 to July 2017 were enrolled. According to whether LVAA was detected by echocardiography, the enrolled patients were divided into two groups: LVAA detected by echocardiography group and LVAA not detected by echocardiography group. Clinical data of the two groups were compared to analyze the causes of missed diagnosis by echocardiography. Results: A total of 21 patients were included, of whom 67.0% (14/21) were males, aged (56.1±16.5) years. Patients with chest discomfort accounted for 81.0% (17/21), palpitation 38.1% (8/21), syncope 14.3% (3/21). ECG showed that 21 (100%) patients had ST-T changes and 18 (85.7%) had deep T-wave invertion. Echocardiography revealed ApHCM in 17 cases (81.0%) and LVAA in 7 cases (33.3%). The mean left ventricular apical aneurysm diameter was 33.0 (18.0, 37.0) mm, and left ventricular ejection fraction was (66.5±6.6) %, and left ventricular apex thickness was (21.0±6.3) mm. Left ventricular outflow tract obstruction was presented in 4 cases and middle left ventricular obstruction in 10 cases. The mean left ventricular apical aneurysm diameter of LVAA detected by echocardiography was greater than that of LVAA not detected by echocardiography (25.0 (18.0, 28.0) mm vs. 16.0 (12.3, 21.0) mm, P=0.006). Conclusions: Conventional echocardiography examination has certain limitations in the diagnosis of ApHCM. Smaller LVAA complicated with ApHCM is likely to be unrecognized by echocardiography. Clinicians should improve their understanding of this disease.
Subject(s)
Apical Hypertrophic Cardiomyopathy , Cardiomyopathy, Hypertrophic , Heart Aneurysm , Male , Humans , Female , Retrospective Studies , Stroke Volume , Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/diagnostic imaging , Ventricular Function, Left , Echocardiography , Heart Aneurysm/complications , Heart Aneurysm/diagnostic imagingABSTRACT
Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0Subject(s)
Cardiomyopathy, Hypertrophic
, Contrast Media
, Humans
, Female
, Adult
, Middle Aged
, Male
, Retrospective Studies
, Stroke Volume
, Gadolinium
, Ventricular Function, Left
, Magnetic Resonance Imaging
, Cardiomyopathy, Hypertrophic/diagnostic imaging
, Death, Sudden, Cardiac
, Risk Assessment
ABSTRACT
Objective: To investigate the treatment and maternal and fetal outcomes of pregnant women with aortic dissection (AD). Methods: The clinical data of 11 pregnant women with AD treated at the First Affiliated Hospital of Air Force Military Medical University from January 1st, 2011 to August 1st, 2022 were collected, and their clinical characteristics, treatment plans and maternal and fetal outcomes were analyzed retrospectively. Results: (1) Clinical characteristics: the age of onset of 11 pregnant women with AD was (30±5) years old, and the week of pregnancy of onset was (31.4±8.0) weeks. Clinical manifestations: the main symptoms were sudden onset of chest and back pain or low back pain. Type of AD: 8 cases of Stanford type A, and 3 cases of type B. The aortic width was (42±11) mm. Diagnostic methods: the diagnosis of AD was confirmed by transthoracic echocardiography (TTE), computed tomography angiography (CTA) or enhanced CT examination, among which 4 cases were confirmed by CTA examination, 4 cases by TTE examination, and 3 cases by enhanced CT examination. Laboratory results: white blood cell count was (15.4±8.7) ×109/L, neutrophil count was (13.5±8.5) ×109/L, the median D-dimer level was 2.7 mg/L (2.1-9.2 mg/L), and the median fibrin degradation products level was 12.0 mg/L (5.4-36.1 mg/L). (2) Treatments: all 11 patients were admitted to hospital in emergency. Before operation, the departments of cardiac surgery, obstetrics, pediatrics and anesthesiology cooperated to develop individualized treatment plan. Aortic surgery was performed in 11 pregnant women with AD. In 6 of them, pregnancy termination was performed at the same time as aortic surgery, and aortic surgery was performed after cesarean section. Four cases of pregnancy termination and aortic operation were performed by stages, including aortic operation after cesarean section in 2 cases, and cesarean section after aortic operation in 2 cases. One case (12+6 weeks of gestation) had spontaneous abortion on the day after aortic surgery. The gestational age of the 11 patients on pregnancy termination was (32.9±7.4) weeks. Aorta surgical methods: 7 patients received under extracorporeal circulation ascending aorta replacement ± aortic valve replacement ± coronary artery transplantation (or coronary artery bypass transplantation)± left and right coronary Cabrol + total arch replacement (or aortic arch replacement)± stent implantation, 1 patient received under extracorporeal circulation aortic root replacement, and 3 patients underwent aortic endoluminal isolation. (3) Maternal and fetal outcomes: among the 11 pregnant women with AD, 9 (9/11) survived, 2 (2/11) died with lower limb ischemia before the onset of the disease. A total of 10 newborns were born in 9 pregnant women after delivery (1 of them was twins), and the 2 cases were spontaneous abortion after aortic surgery in the first trimester (12+6 weeks) and fetal death after hysterotomy in the second trimester (26+3 weeks), respectively. Among the 10 surviving neonates, 3 were full-term infants and 7 were premature infants. The birth weight of newborn was (2 651±784) g. Respiratory distress syndrome was found in 6 cases. The newborns were followed up for (5.6±3.6) years after birth, and the infants developed well during the follow-up period. Conclusions: Pregnancy complicated with AD is dangerous, and chest and back pain is the main clinical manifestation of this disease. With early identification and selection of appropriate diagnostic methods, multidisciplinary diagnosis and treatment, mother and children could obtain good outcomes.
Subject(s)
Abortion, Spontaneous , Aortic Dissection , Infant , Pregnancy , Infant, Newborn , Humans , Female , Child , Adult , Cesarean Section , Retrospective Studies , Aortic Dissection/diagnosis , Aortic Dissection/surgery , Fetal DeathABSTRACT
Objective: To investigate the effects of tumor necrosis factor-alpha (TNF-α)/extracellular signal-regulated kinase (ERK) pathway on the migration ability of HaCaT cells and full-thickness skin defects in mice. Methods: The experimental research method was adopted. According to the random number table (the same below), HaCaT cells were divided into the normal oxygen group and the hypoxia group cultured under hypoxia (with oxygen volume fraction of 1%, the same below) condition. After 24 hours of culture, the significantly differentially expressed genes between the 2 groups were screened using the microarray confidence analysis software SAM4.01. The significance of the number of each gene in the signaling pathway was analyzed through the Kyoto encyclopedia of genes and genomes to screen the significantly differentially signaling pathways (n=3). HaCaT cells were cultured for 0 (immediately), 3, 6, 12, and 24 h under hypoxia condition. The secretion level of TNF-α was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 5. HaCaT cells were divided into normal oxygen group, hypoxia alone group, and hypoxia+inhibitor group cultured with FR180204 (an ERK inhibitor) and under hypoxia condition. The cells were cultured for 3, 6, 12, and 24 h. The migration ability of the cells was detected by scratch test (n=12). The expressions of phosphorylated nuclear factor kappa B (p-NF-κB), phosphorylated p38 (p-p38), phosphorylated ERK1/2 (p-ERK1/2), N-cadherin, and E-cadherin in HaCaT cells were detected by Western blotting under hypoxic condition for 0, 3, 6, 12, and 24 h (n=3). Sixty-four BALB/c male mice aged 6 to 8 weeks were used to make a full-thickness skin defect wound model on the dorsum of the mice. The mice were divided into the blank control group and the inhibitor group treated with FR180204, with 32 mice in each group being treated accordingly. On post injury day (PID) 0, 3, 6, 9, 12, and 15, the wound conditions of mice were observed and the healing rate was calculated (n=8). On PID 1, 3, 6, and 15, hematoxylin-eosin staining was used to observe neovascularization, inflammatory cell infiltration, and epidermal regeneration on wound, Masson staining was used to observe collagen deposition on wound, the expressions of p-NF-κB, p-p38, p-ERK12, N-cadherin, and E-cadherin in wound tissue were detected by Western blotting (n=6), the number of Ki67 positive cells and the absorbance value of vascular endothelial growth factor (VEGF) were detected by immunohistochemistry (n=5), the protein expressions of interleukin 6 (IL-6), IL-10, IL-1ß, and CCL20 in wound tissue were detected by ELISA (n=6). Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, factorial design analysis of variance, Tukey test, least significant difference test, and independent sample t test. Results: After 24 hours of culture, compared with normal oxygen group, 7 667 genes were up-regulated and 7 174 genes were down-regulated in cells in hypoxic group. Among the above differentially expressed genes, the TNF-α signaling pathway had significant change (P<0.05) with large number of genes. Under hypoxia condition, the expression of TNF-α at 24 h of cell culture was (11.1±2.1) pg/mL, which was significantly higher than (1.9±0.3) pg/mL at 0 h (P<0.05). Compared with normal oxygen group, the migration ability of cells in hypoxia alone group was significantly enhanced at 6, 12, and 24 h of cell culture (with t values of 2.27, 4.65, and 4.67, respectively, P<0.05). Compared with hypoxia alone group, the migration ability of cells in hypoxia+inhibitor group was significantly decreased at 3, 6, 12, and 24 h of cell culture (with t values of 2.43, 3.06, 4.62, and 8.14, respectively, P<0.05). Under hypoxia condition, the expressions of p-NF-κB, p-ERK1/2, and N-cadherin were increased significantly at 12 and 24 h of cell culture compared with 0 h of culture (P<0.05), the expression of p-p38 was significantly increased at 3, 6, 12, and 24 h of cell culture (P<0.05), the expression of E-cadherin was significantly decreased at 6, 12, and 24 h of cell culture (P<0.05), the expression of p-ERK1/2, p-NF-κB, and E-cadherin was time-dependent. Compared with blank control group, on PID 3, 6, 9, 12, and 15, the wound healing rate of mice in inhibitor group was significantly decreased (P<0.05); there were more inflammatory cell infiltration around the wound edge of mice in inhibitor group on PID 3, 6, and 15, especially on PID 15, a large number of tissue necrosis and discontinuous new epidermal layer were observed on the wound surface, and collagen synthesis and new blood vessels were reduced; the expression of p-NF-κB in the wound of mice in inhibitor group was significantly decreased on PID 3 and 6 (with t values of 3.26 and 4.26, respectively, P<0.05) but significantly increased on PID 15 (t=3.25, P<0.05), the expressions of p-p38 and N-cadherin were significantly decreased on PID 1, 3, and 6 (with t values of 4.89, 2.98, 3.98, 9.51, 11.69, and 4.10, respectively, P<0.05), the expression of p-ERK1/2 was significantly decreased on PID 1, 3, 6, and 15 (with t values of 26.69, 3.63, 5.12, and 5.14, respectively, P<0.05), the expression of E-cadherin was significantly decreased on PID 1 (t=20.67, P<0.05) but significantly increased on PID 6 (t=2.90, P<0.05); the number of Ki67 positive cells and absorbance value of VEGF of wound in inhibitor group were significantly decreased on PID 3, 6, and 15 (with t values of 4.20, 7.35, 3.34, 4.14, 3.20, and 3.73, respectively, P<0.05); the expression of IL-10 in the wound tissue of the inhibitor group was significantly decreased on PID 6 (t=2.92, P<0.05), the expression of IL-6 was significantly increased on PID 6 (t=2.73, P<0.05), the expression of IL-1ß was significantly increased on PID 15 (t=3.46, P<0.05), and CCL20 expression levels were significantly decreased on PID 1 and 6 (with t values of 3.96 and 2.63, respectively, P<0.05) but significantly increased on PID 15 (t=3.68, P<0.05). Conclusions: The TNF-α/ERK pathway can promote the migration of HaCaT cells, and regulate the healing of full-thickness skin defect wounds in mice by affecting the expression of inflammatory cytokines and chemokines.
Subject(s)
Interleukin-10 , Tumor Necrosis Factor-alpha , Male , Animals , Mice , Humans , Vascular Endothelial Growth Factor A , Extracellular Signal-Regulated MAP Kinases , HaCaT Cells , Interleukin-6 , Ki-67 Antigen , NF-kappa B , Hypoxia , OxygenABSTRACT
Objective: This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed. Results: Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) . Conclusions: Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.
Subject(s)
Antibodies, Monoclonal , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Pneumonia , Male , Female , Humans , Middle Aged , Aged , Multiple Myeloma/drug therapy , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Transplantation, Autologous , Pneumonia/etiology , Dexamethasone , Bortezomib/therapeutic useABSTRACT
Objective: To investigate the dynamic change of the secundum atrial septal defect (ASD) throughout the cardiac cycle, and assess its impact on occluder selection. Methods: This study retrospectively analyzed 35 patients with ASD who received electrocardiogram-gated coronary CT angiography (CCTA) throughout the cardiac cycle as well as interventional closure therapy in Fuwai Hospital from December 2016 to December 2019. The raw data were reconstructed into 20 phasic images of RR intervals (RRI) ranging from 0 to 95% in an increment of 5% and transmitted to a workstation for postprocessing. For each phase image, CT virtual endoscopy reconstruction technique (CTVE) was used to provide views of ASD. Axial sequence assisted CT volumetric measurement (CTAS) was used to calculate the maximum dimensions in axial planes (Da) and in superior-inferior direction (Db). Using a formula for converting circumference to diameter, the equivalent circle dimensions were calculated (De, De=minor axis+2 (major axis-minor axis)/3). Taking the data of 75% RRI phase, the patients were divided into Da75%RRI≥Db75%RRI group and Da75%RRI