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Communications Medicine Jul 2024Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an inhibitory cell surface protein that functions through homophilic and heterophilic ligand...
BACKGROUND
Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an inhibitory cell surface protein that functions through homophilic and heterophilic ligand binding. Its expression on immune cells in human tumors is poorly understood.
METHODS
An antibody that distinguishes human CEACAM1 from other highly related CEACAM family members was labeled with Tb and inserted into a panel of antibodies that included specificity for programmed cell death protein 1 (PD1) and PD-L1, which are targets of immunotherapy, to gain a data-driven immune cell atlas using cytometry by time-of-flight (CyTOF). A detailed inventory of CEACAM1, PD1, and PD-L1 expression on immune cells in metastatic lesions to lymph node or soft tissues and peripheral blood samples from patients with treatment-naive and -resistant melanoma as well as peripheral blood samples from healthy controls was performed.
RESULTS
CEACAM1 is absent or at low levels on healthy circulating immune cells but is increased on immune cells in peripheral blood and tumors of melanoma patients. The majority of circulating PD1-positive NK cells, innate T cells, B cells, monocytic cells, dendritic cells, and CD4 T cells in the peripheral circulation of treatment-resistant disease co-express CEACAM1 and are demonstrable as discrete populations. CEACAM1 is present on distinct types of cells that are unique to the tumor microenvironment and exhibit expression levels that are highest in treatment resistance; this includes tumor-infiltrating CD8 T cells.
CONCLUSIONS
To the best of our knowledge, this work represents the first comprehensive atlas of CEACAM1 expression on immune cells in a human tumor and reveals an important correlation with treatment-resistant disease. These studies suggest that agents targeting CEACAM1 may represent appropriate partners for PD1-related pathway therapies.
PubMed: 38956268
DOI: 10.1038/s43856-024-00525-8 -
Cell Death & Disease Jul 2024Colorectal cancer (CRC) is one of the most common tumors of the digestive system worldwide. KRAS mutations limit the use of anti-EGFR antibodies in combination with...
Colorectal cancer (CRC) is one of the most common tumors of the digestive system worldwide. KRAS mutations limit the use of anti-EGFR antibodies in combination with chemotherapy for the treatment of CRC. Therefore, novel targeted therapies are needed to overcome the KRAS-induced oncogenesis. Recent evidence suggests that inhibition of PI3K led to ferroptosis, a nonapoptotic cell death closely related to KRAS-mutant cells. Here, we showed that a selective PI3Kδ inhibitor TYM-3-98 can suppress the AKT/mTOR signaling and activate the ferroptosis pathway in KRAS-mutant CRC cells in a concentration-dependent manner. This was evidenced by the lipid peroxidation, iron accumulation, and depletion of GSH. Moreover, the overexpression of the sterol regulatory element-binding protein 1 (SREBP1), a downstream transcription factor regulating lipid metabolism, conferred CRC cells greater resistance to ferroptosis induced by TYM-3-98. In addition, the effect of TYM-3-98 was confirmed in a xenograft mouse model, which demonstrated significant tumor suppression without obvious hepatoxicity or renal toxicity. Taken together, our work demonstrated that the induction of ferroptosis contributed to the PI3Kδ inhibitor-induced cell death via the suppression of AKT/mTOR/SREBP1-mediated lipogenesis, thus displaying a promising therapeutic effect of TYM-3-98 in CRC treatment.
Topics: Ferroptosis; Humans; Colorectal Neoplasms; TOR Serine-Threonine Kinases; Animals; Proto-Oncogene Proteins c-akt; Sterol Regulatory Element Binding Protein 1; Lipogenesis; Proto-Oncogene Proteins p21(ras); Mice; Signal Transduction; Mice, Nude; Cell Line, Tumor; Mutation; Xenograft Model Antitumor Assays; Mice, Inbred BALB C; Class I Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors
PubMed: 38956060
DOI: 10.1038/s41419-024-06848-7 -
CEN Case Reports Jul 2024A 76-year-old woman was admitted with progressive renal function decline. A kidney biopsy was performed because of myeloperoxidase anti-neutrophil cytoplasmic antibody...
A 76-year-old woman was admitted with progressive renal function decline. A kidney biopsy was performed because of myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA; 333 IU/mL), proteinuria (1.21 g/d), and urinary erythrocyte sediment (10-19/high-power field). Renal-limited ANCA-positive vasculitis with pauci-immune necrotizing crescentic glomerulonephritis (ANCA-associated vasculitis, AAV) was diagnosed. Glucocorticoid therapy was started, and the patient responded well. About 1 year later, avacopan treatment was started and glucocorticoid therapy was discontinued. Avacopan did not normalize ANCA levels and did not make urinary findings negative. However, further progression of renal function decline is prevented. Factors attributed to the development of AAV in this case were investigated; AAV developed after the second dose of the COVID-19 vaccine and ANCA levels re-elevated after the fifth dose. This suggests that the COVID-19 vaccine may have contributed to the development of AAV in this elderly patient. Avacopan monotherapy has been shown to be effective as maintenance therapy to control the progression of renal failure although not sufficient for complete remission of AAV.
PubMed: 38955948
DOI: 10.1007/s13730-024-00910-1 -
Strahlentherapie Und Onkologie : Organ... Jul 2024Glofitamab, an anti-CD20 antibody, is approved as a third-line treatment for relapsed or refractory (r/r) diffuse large-cell B lymphoma (DLBCL), achieving a complete...
Glofitamab, an anti-CD20 antibody, is approved as a third-line treatment for relapsed or refractory (r/r) diffuse large-cell B lymphoma (DLBCL), achieving a complete response in nearly 40% of patients. This humanized IgG1 bispecific monoclonal antibody binds to CD20 on malignant B lymphocytes and to CD3 on cytotoxic T cells. This dual binding forms an immunological synapse, activating T lymphocytes and leading to the lysis of tumor cells. Salvage radiotherapy is also effective for r/r DLBCL, but its combination with systemic treatments like glofitamab may increase radiation-induced toxicity. We report the first case of a patient with r/r DLBCL receiving concurrent salvage radiotherapy and glofitamab. A 68-year-old female diagnosed with stage IV DLBCL underwent initial treatment with R-CHOP, then Car-T cell therapy, followed by glofitamab for recurrence. Upon early metabolic progression detected by 18FDG-PET/CT, salvage radiotherapy was administered to the refractory site concurrently with glofitamab. The patient experienced mild para-spinal pain post-radiotherapy but no other significant toxicities. Three months post-treatment, she showed a complete metabolic response with no radiotherapy toxicity, as evidenced by PET-CT, and no signs of radiation pneumonitis. This case indicates that combining glofitamab with salvage radiotherapy is tolerable and suggests potential efficacy, warranting further investigation in prospective studies for r/r DLBCL.
PubMed: 38955824
DOI: 10.1007/s00066-024-02256-0 -
[Zhonghua Yan Ke Za Zhi] Chinese... Jul 2024To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). This was a... (Randomized Controlled Trial)
Randomized Controlled Trial
To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group -test were used for statistical analysis. Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups (>0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)μm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)μm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all >0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, >0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; <0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm, significantly different from that in the combination therapy group [(0.34±0.16) mm] at 12 months (<0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.
Topics: Humans; Macular Edema; Diabetic Retinopathy; Ranibizumab; Prospective Studies; Treatment Outcome; Intravitreal Injections; Visual Acuity; Angiogenesis Inhibitors; Laser Coagulation; Female; Male; Middle Aged; Fluorescein Angiography
PubMed: 38955759
DOI: 10.3760/cma.j.cn112142-20231227-00314 -
Zhonghua Jie He He Hu Xi Za Zhi =... Jul 2024Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset... (Review)
Review
Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset and lacks specific clinical manifestations, and its manifestations are closely related to the growth mode, location and size of the tumor. It can involve multiple parts, such as the larynx, trachea, bronchus, and lung parenchyma, which cause coughing, hoarseness, dysphonia, and, in severe cases, may lead to obstruction of the respiratory tract. At present, the treatment of respiratory papilloma lacks standardization, and there is no effective method to cure the disease. Surgery remains the main treatment for alleviating patients' symptoms and preventing airway obstruction. However, due to the high recurrence rate of respiratory papilloma, multiple surgeries are often needed, which reduces the quality of life of patients and increases their disease burden and economic burden. Bevacizumab, a vascular endothelial growth factor-binding antibody inhibitor, is a promising adjuvant treatment modality that shows good potential for reducing symptoms and the frequency of surgery. This article aimed to review the efficacy and safety of bevacizumab for the treatment of respiratory papilloma and discuss the differences and efficacy of the systemic application and intralesional injection of bevacizumab for the treatment of respiratory papilloma.
Topics: Humans; Bevacizumab; Papilloma; Respiratory Tract Neoplasms; Angiogenesis Inhibitors
PubMed: 38955756
DOI: 10.3760/cma.j.cn112147-20231220-00383 -
Zhonghua Jie He He Hu Xi Za Zhi =... Jul 2024The prevalence of pulmonary aspergillosis is increasing in patients with chronic obstructive pulmonary disease (COPD) and can manifest in different forms such as...
The prevalence of pulmonary aspergillosis is increasing in patients with chronic obstructive pulmonary disease (COPD) and can manifest in different forms such as invasive pulmonary aspergillosis (IPA), chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). With the variations of individual conditions such as immune status, these forms of the disease may transform into each other or even overlap. Moreover, the atypical clinical manifestations and the limited use of invasive sampling techniques have posed a challenge to the diagnosis and treatment of invasive pulmonary aspergillosis in patients with COPD. To provide recommendations for the management of pulmonary aspergillosis in patients with COPD and to construct a clinical workflow, the consensus panel reviewed the evidence and critically appraised the existing studies. As the majority of the recommendations were supported by low levels of evidence, the evidence levels were not listed in the consensus and the strong and weak recommendations were expressed as "recommend" and "suggest", respectively.Recommendations for COPD with IPA: The Panel recommends that high-resolution chest computed tomography (HRCT) be performed in patients suspected with IPA. If IPA cannot be excluded by CT scanning, mycological examination of sputum and bronchoalveolar lavage fluid (BALF) is recommended. Bronchoscopy and BALF -related examination are recommended in COPD patients with respiratory symptoms such as dyspnea despite the use of broad-spectrum antibiotics and systemic glucocorticoids and pulmonary infiltrates observed on chest CT. If the diagnosis is in doubt in patients with probable IPA, histopathological examination is recommended. In COPD patients with an acute infection of more than 10 days' duration, the Panel recommended the detection of -specific IgG antibodies in peripheral blood to aid in the diagnosis of IPA, especially in those who cannot obtain BALF. It is not recommended to initiate antifungal therapy based on clinical symptoms such as cough, fever, and dyspnea empirically in COPD patients. In critically ill patients (such as those admitted to ICU and those with respiratory failure) who are unresponsive to broad-spectrum antibiotic treatment and have imaging findings consistent with IPA, patients with HRCT or bronchoscopy findings consistent with airway invasive aspergillosis, patients with a history of oral or intravenous glucocorticoid use in the past 3 months, or patients with a history of airway infection or colonization, empirical antifungal therapy may be initiated after a comprehensive evaluation of infection risk, and at the same time, pathogen examination should be started as early as possible. Voriconazole, isavuconazole, and posaconazole are recommended as the first-line treatments for COPD with IPA. Echinocandins and amphotericin B may be used as alternative options. Antifungal treatment for COPD with IPA should be continued for at least 6-12 weeks. The duration of antifungal therapy should be determined based on clinical symptoms, pulmonary imaging, and microbiological test results. Significant lesion absorption and stabilization, as well as the elimination of related risk factors, are important references for discontinuation of treatment.Recommendations on COPD with CPA: Chest CT scan and dynamic observation are recommended for COPD with suspected CPA. Peripheral blood -specific IgG antibody testing is recommended in COPD patients with suspected CPA. For those who are difficult to diagnose by routine methods or need further differential diagnosis, pulmonary tissue histopathological examination is recommended. Oral itraconazole solution or voriconazole tablets are recommended as the first-line treatment options for COPD with CPA. Oral isavuconazole capsules or enteric-coated posaconazole tablets can be used as an alternative. Intravenous administration of echinocandins or amphotericin B (deoxycholate or lipid formulations) are suggested as a second-line treatment options in cases of triazole treatment failure, resistance, or intolerance. Antifungal treatment for COPD with CPA should be continued for at least 6 months, and for patients with CCPA for at least 9 months. In those with cavities communicating with the bronchial lumen, if systemic antifungal therapy is ineffective or cannot be tolerated due to adverse reactions, and surgery is also not feasible, the Panel suggests considering nebulized inhalation of amphotericin B and intracavitary injection of amphotericin B or azoles (voriconazole, itraconazole) to control recurrent hemoptysis.Recommendations on COPD with sensitization: When COPD patients present with refractory wheezing and/or rapid decline in lung function, it is recommended that an assessment for sensitization be performed, including -specific IgE, skin antigen test, -specific IgG, total IgE, blood eosinophil count, and sputum examination. The Panel recommends that antifungal therapy should not be routinely initiated in COPD patients with sensitization. For those who meet the diagnostic criteria for ABPA, antifungal therapy is suggested. The most commonly used medication is oral itraconazole solution, but other azoles such as voriconazole, isavuconazole and posaconazole enteric-coated tablets can also be chosen. The general course of antifungal therapy is 3-6 months.Recommendations on the use of glucocorticoids in COPD with pulmonary aspergillosis: In exacerbating COPD patients with secondary IPA or subacute invasive aspergillosis, the Panel suggests that the use of glucocorticoids should be controlled. For COPD patients with concomitant CPA who experience exacerbations with predominantly wheezing, it is suggested that short-term, low-dose glucocorticoids be considered on the basis of antifungal treatment to control symptoms. Glucocorticoid use for COPD exacerbations is suggested to be guided by peripheral blood eosinophil count. It is recommended to avoid systemic glucocorticoids and long-term or high-dose inhaled glucocorticoids (ICS) in stable COPD patients with concomitant CPA. In patients with concomitant sensitization and persistent wheezing despite standardized COPD treatment or patients with ABPA, the Panel recommends systemic glucocorticoids in combination with antifungal therapy and consideration of the use of ICS to reduce the dose of systemic glucocorticoids. Close monitoring for progression to IPA or subacute invasive aspergillosis is essential during treatment.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Aspergillosis; Consensus
PubMed: 38955746
DOI: 10.3760/cma.j.cn112147-20231228-00399 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain...
To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using -test and Mann-Whitney -test. After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:=-2.298, <0.05; DM-SCIT:=-3.411, <0.001); total ACT score (SM-SCIT:=-2.054, <0.05; DM-SCIT:=-2.014, <0.05) and total medication scores (SM-SCIT:=-3.799, <0.000 1; DM-SCIT:=-3.474, <0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (=-2.253, <0.05). There was no significant change in sIgE in the SM-SCIT group (>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all <0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all <0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all <0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all <0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (=-1.988, -2.090, -2.497, -1.988, respectively, all <0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (-0.499, <0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (=0.451, 0.420, 0.474, respectively; all <0.05). Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.
Topics: Humans; Fatty Acids, Unsaturated; Animals; Desensitization, Immunologic; Asthma; Pyroglyphidae; Longitudinal Studies; Antigens, Dermatophagoides; Allergens; Child; Injections, Subcutaneous; Immunoglobulin E
PubMed: 38955724
DOI: 10.3760/cma.j.cn112150-20240124-00083 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and...
To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance. Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups. A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant (=1.541 for local adverse reactions in the control group, =0.718 for the observation group; =0.483 for systemic adverse reactions in the control group, =0.179 for the observation group, value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups (=4.147, <0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status (-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all -values <0.001, and -values of the observation group were 15.480, 27.087, 28.938, all -values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment (-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all -values <0.001, and -values of 9.436, 13.184, and 22.377 in the observation group, respectively; all -values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years (-values 0.621, 0.473, 1.825, and 0.342, respectively, and -values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points (-values of 1.663, 0.095, 0.305, 0.951, -values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment (-values of the conventional group were 3.453, 5.469, 6.273, -values <0.05, and the -values of the observation group were 2.900, 4.575, 5.988, -values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing (-value in the conventional group was -5.328, -4.254, -0.690, -value was 0.000, 0.000, 0.492, respectively, and -value in the observation group was -6.087, -5.087, -0.324, -value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years (-values of 0.723, 1.553, 0.766, and 0.234, respectively; -values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE (-values of 0.170, -0.166, -0.449, 0.839, -values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 (-values 1.507, 1.467, -0.337, 0.804, -values 0.134, 0.145, 0.737, 0.422, respectively). Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.
Topics: Humans; Child; Desensitization, Immunologic; Retrospective Studies; Child, Preschool; Adolescent; Animals; Immunoglobulin E; Asthma; Allergens; Male; Rhinitis, Allergic; Female; Mites; Treatment Outcome
PubMed: 38955723
DOI: 10.3760/cma.j.cn112150-20230915-00194 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024To evaluate the effectiveness and safety of treatment with Burosumab in pediatric X-linked hypophosphatemia (XLH) patients. In this retrospective case study, 4...
To evaluate the effectiveness and safety of treatment with Burosumab in pediatric X-linked hypophosphatemia (XLH) patients. In this retrospective case study, 4 children with pediatric XLH, who were treated with Burosumab in Beijing Children's Hospital, Capital Medical University and Shandong Provincial Hospital affiliated to Shandong First Medical University from July 2022 to December 2023, were selected as the study objects. We collected and analyzed their clinical characteristics, biochemical indicators, imaging results, and treatment. The children were followed up every 3 months until December 2023, and the clinical outcomes and adverse drug reactions after treatment were evaluated. Of the 4 patients, 3 were males and 1 was female; they were aged 6.7, 2.9, 2.1, and 2.3 years, respectively. Three patients had previously received treatment with phosphate supplements and active vitamins, but their wadding gait and lower limb deformities did not improve significantly, neither did their imaging changes of active richets. The initial dose of Burosumab in the 4 patients was 0.8 mg/kg, administered subcutaneously every 2 weeks, with a treatment course of 0.8-1.3 years. The fasting serum phosphorus and tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) of the 4 patients before treatment were 0.72, 0.95, 0.81, 0.66 mmol/L and 0.67, 0.85, 0.87, 0.61 mmol/L, respectively. At the last follow-up, the fasting serum phosphorus and TmP/GFR levels were significantly increased (0.96, 1.09, 1.09, 0.90 mmol/L, and 0.85, 0.79, 1.03, 0.98 mmol/L, respectively). Among them, only the TmP/GFR level (1.17 mmol/L) in case 2 achieved normal values at 3 months post-therapy, while the rest did not reach the normal range for children of the same age. After treatment, the alkaline phosphatase levels of all patients gradually decreased (the values were 461, 240, 423, and 237 U/L, respectively), and the ALP levels in cases 2 and 4 returned to normal at the last visit. Case 4 showed a slight increase in parathyroid hormone (PTH) levels after 9 months of treatment, while the PTH levels in the rest 3 cases remained normal. Case 1 underwent a 6-minute walking test, and the walking distance increased from 245 m to 570 m. Abnormal gait, lower limb deformity, and the severity of rickets in the 4 patients had all improved. No adverse drug reactions such as nephrocalcinosis, local skin injection reaction, hyperphosphatemia, or vitamin D deficiency were observed. Burosumab can improve clinical symptoms in children with XLH with a good safety profile.
Topics: Humans; Male; Female; Familial Hypophosphatemic Rickets; Antibodies, Monoclonal, Humanized; Child; Retrospective Studies; Child, Preschool; Treatment Outcome
PubMed: 38955688
DOI: 10.3760/cma.j.cn112140-20231201-00404