-
Cardiovascular and Interventional... Jul 2024To report response rates (using mRECIST), overall survival (OS), progression-free survival and local tumour recurrence-free survival (LRFS) of balloon-occluded...
PURPOSE
To report response rates (using mRECIST), overall survival (OS), progression-free survival and local tumour recurrence-free survival (LRFS) of balloon-occluded transarterial chemoembolisation (bTACE) for hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
Patients from five European centres treated with conventional or drug-eluting microsphere bTACE for HCC were included, and patients already lost to follow-up before 12 months were excluded. Possible factors contributing to LRFS and OS were evaluated with Cox proportional hazards models.
RESULTS
Seventy-three patients were enrolled. The mean number of nodules per patient was 2.07(± 1.68), and the average maximum diameter of the nodules was 37 ± 19.9 mm. The response of the target lesion at 6 months was complete response (CR) in 58.9%, partial response (PR) in 28.8%, stable disease (SD) in 6.8% and progressive disease (PD) in 5.5%. The median follow-up time was 31 months; at the last follow-up, target tumour response was CR in 49.3%, PR in 12.3%, SD in 5.5% and PD 32.9%. Overall response at the last follow-up was CR in 17.8%, PR in 9.6%, SD 2.7% and PD in 69.9% (for new lesions in 37% of patients). Median OS was not reached; mean overall survival was 50.0 months, while median LRFS was 31.0 months. At uni- and multivariable analysis, only tumour maximum diameter was related to LRFS (hazard ratio [HR] = 1.021; 95% CI 1.004-1.038, P = 0.015).
CONCLUSIONS
bTACE demonstrated high efficacy for HCC, with a complete response in 58.9% of patients, a median local recurrence-free survival of 31.0 months and a mean overall survival of 50.0 months.
PubMed: 38955814
DOI: 10.1007/s00270-024-03779-w -
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 evaluate the modification of allergic dermatitis on the association between PM exposure and allergic rhinitis in preschool children. This cross-sectional study was...
To evaluate the modification of allergic dermatitis on the association between PM exposure and allergic rhinitis in preschool children. This cross-sectional study was based on a questionnaire conducted between June 2019 and June 2020 to caregivers of children aged 3 to 6 years in the kindergartens of 7 Chinese cities to collect information on allergic rhinitis and allergic dermatitis. A mature machine learning-based space-time extremely randomized trees model was applied to estimate early-life, prenatal, and first-year exposure of PM, PM and PM at 1 km×1 km resolution. A combination of multilevel logistic regression and restricted cubic spline functions was used to quantitatively assess whether allergic dermatitis modifies the associations between size-specific PM exposure and the risk of childhood allergic rhinitis. The results showed that out of 28 408 children, 14 803 (52.1%) were boys and 13 605 (47.9%) were girls; the age of children ranged from 3.1 to 6.8 years, with a mean age of (4.9±0.9) years, of which 3 586 (12.6%) were diagnosed with allergic rhinitis. Among all children, 17 832 (62.8%) were breastfed for more than 6 months and 769 (2.7%) had parental history of atopy. A total of 21 548 children (75.9%) had a mother with an educational level of university or above and 7 338 (29.6%) had passive household cigarette smoke exposure. The adjusted s for childhood allergic rhinitis among the children with allergic dermatitis as per interquartile range (IQR) increase in early-life PM(9.8 μg/m), PM (14.9 μg/m) and PM (37.7 μg/m) were significantly higher than the corresponding s among the children without allergic dermatitis [: 1.45, 95% (1.26, 1.66) 1.33, 95% (1.20, 1.47), for PM; : 1.38, 95% (1.23, 1.56) 1.32, 95% (1.21, 1.45), for PM; : 1.56, 95% (1.31, 1.86) 1.46, 95% (1.28, 1.67), for PM]. The interactions between allergic dermatitis and size-specific PM exposure on childhood allergic rhinitis were statistically significant ( value=19.4, all for interaction<0.001). The similar patterns were observed for both prenatal and first-year size-specific PM exposure and the results of the dose-response relationship were consistent with those of the logistic regression. In conclusion, allergic dermatitis, as an important part of the allergic disease progression, may modify the association between ambient PM exposure and the risk of childhood allergic rhinitis. Children with allergic dermatitis should pay more attention to minimize outdoor air pollutants exposure to prevent the further progression of allergic diseases.
Topics: Humans; Particulate Matter; Child, Preschool; Rhinitis, Allergic; Female; Cross-Sectional Studies; Dermatitis, Atopic; China; Male; Environmental Exposure; Child; Air Pollutants; Particle Size; Air Pollution; Risk Factors; Logistic Models
PubMed: 38955730
DOI: 10.3760/cma.j.cn112150-20230915-00192 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jul 2024To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF). The clinical...
To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF). The clinical morphological and immunohistochemical features of 7 NMC-DF cases diagnosed from January 2013 to January 2023 in Beijing Jishuitan Hospital were retrospectively analyzed. A series of neuromuscular choristoma and neuromuscular choristoma-associated desmoid type fibromatosis were evaluated for CTNNB1 mutations, and hotspot mutations for CTNNB1 were tested in 4 NMC-DF cases using Sanger sequencing. The tumors were collected from 3 females and 4 males, aged 1 to 22 years (mean 7.1 years), involving the sciatic nerve (=4), brachial plexus (=2) or multiple nerves (=1). The course of the disease spanned from 3 months to 10 years. Two cases were recurrent tumors. All the 7 NMC cases showed endoneurial intercalation of mature skeletal muscle fibers among the peripheral nerve fascicles, and the histologic features of the NMC-DF were strikingly similar to the conventional desmoid-type fibromatosis. By immunohistochemistry, all NMC and NMC-DF cases showed aberrant nuclear staining of β-catenin (7/7), the muscle cells in NMC were intensely immunoreactive for desmin, and the admixed nerve fibers were highlighted by NF and S-100 (7/7). Four NMC and NMC-DF had CTNNB1 mutations, 3 c.121A>G (p.T41A) and 1 c.134C>T (p.S45F). Follow-up of the 7 cases, ranging from 22 to 78 months, showed tumor recurrence in 2 patients at 3 and 8 months respectively after the first surgical resection, of which 1 patient underwent above-knee amputation. No recurrence occurred in other cases with tumor excision and neurological reconstruction surgery. There was no metastasis occurred in the 7 cases. NMC is a rare congenital lesion with differentiated mature skeletal muscle tissue found in peripheral nerve fascicles, and approximately 80% of patients with NMC develop a soft tissue fibromatosis. CTNNB1 mutation in the Wnt signaling pathway may be involved in the pathogenesis of NMC and NMC-DF, and S45F mutations seems to have a higher risk of disease progression.
Topics: Humans; beta Catenin; Fibromatosis, Aggressive; Male; Female; Child; Retrospective Studies; Infant; Adolescent; Child, Preschool; Mutation; Choristoma; Young Adult; Brachial Plexus; Sciatic Nerve
PubMed: 38955699
DOI: 10.3760/cma.j.cn112151-20231026-00310 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a...
To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a basis for subsequent genetic diagnosis. The clinical data of a 5-year-old child with cholestatic liver disease admitted to the Beijing Children's Hospital of Capital Medical University was retrospectively analyzed. The pathogenic variations were detected by whole exome sequencing and verified by Sanger sequencing, and bioinformatics was used to predict the pathogenicity of the mutation sites. Possible pathogenic variations were verified in vitro by Minigene assay. The clinical outcome was followed after discharge from hospital. The 5-year-old boy had developed cholestasis at the age of 11 months. His physical examination showed obvious enlargement of the liver and spleen. Cholestatic cirrhosis was diagnosed by liver function tests, abdominal ultrasonography, liver biopsy and pathology. The results of genetic analysis showed that the patient was a complex heterozygote of the ABCB4 gene, with a pathogenic mutation c.2860G>A and a novel mutation c.2065-8T>G, derived from the mother and father respectively. The conservative prediction of the c.2065-8T>G site showed that this region was highly conserved and may affect splicing. Minigene assay results confirmed that the c.2065-8T>G mutation resulted in a 7 bp retention of intron 16 in the mature mRNA. In the absence of nonsense-mediated mRNA decay, the amino acid frameshift forms a truncated protein, which is represented by p.Glu689ValfsTer19. The patient was diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3) and treated with ursodeoxycholic acid (UDCA). His clinical symptoms improved during 18 months of follow-up. The c.2065-8T>G variant is confirmed to affect the splicing process and exhibits complex heterozygosity with c.2860G>A, which is identified as the cause of the disease. PFIC3 children with this variant showed cholestatic liver disease as the main manifestation with a slow progression and was sensitive to treatment with UDCA.
Topics: Humans; Male; Cholestasis, Intrahepatic; Child, Preschool; ATP Binding Cassette Transporter, Subfamily B; Mutation; Phenotype; Exome Sequencing; Genotype; Heterozygote; Retrospective Studies; Ursodeoxycholic Acid; Liver
PubMed: 38955683
DOI: 10.3760/cma.j.cn112140-20240319-00190 -
Physiological Reports Jul 2024Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 cytokine family, has renoprotective effects in mouse models of acute kidney disease and tubulointerstitial...
Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 cytokine family, has renoprotective effects in mouse models of acute kidney disease and tubulointerstitial fibrosis, but its role in glomerular disease is unknown. To address this, we used the mouse model of nephrotoxic nephritis to test the hypothesis that CT-1 also has a protective role in immune-mediated glomerular disease. Using immunohistochemistry and analysis of single-cell RNA-sequencing data of isolated glomeruli, we demonstrate that CT-1 is expressed in the glomerulus in male mice, predominantly in parietal epithelial cells and is downregulated in mice with nephrotoxic nephritis. Furthermore, analysis of data from patients revealed that human glomerular disease is also associated with reduced glomerular CT-1 transcript levels. In male mice with nephrotoxic nephritis and established proteinuria, administration of CT-1 resulted in reduced albuminuria, prevented podocyte loss, and sustained plasma creatinine, compared with mice administered saline. CT-1 treatment also reduced fibrosis in the kidney cortex, peri-glomerular macrophage accumulation and the kidney levels of the pro-inflammatory mediator complement component 5a. In conclusion, CT-1 intervention therapy delays the progression of glomerular disease in mice by preserving kidney function and inhibiting renal inflammation and fibrosis.
Topics: Animals; Male; Cytokines; Mice; Kidney Glomerulus; Mice, Inbred C57BL; Disease Models, Animal; Humans; Fibrosis; Glomerulonephritis
PubMed: 38955668
DOI: 10.14814/phy2.16129 -
Physiological Reports Jul 2024Latent associations between low serum amylase and reduced plasma insulin levels and increased adiposity have been described previously in a small study of asymptomatic...
Latent associations between low serum amylase and reduced plasma insulin levels and increased adiposity have been described previously in a small study of asymptomatic middle-aged humans. In the present study, we sought to determine the nature of such changes during the longitudinal progression from metabolically normal to overt type 2 diabetes mellitus (T2DM) in nonhuman primates (NHPs), a disease that appears to be the same in both pathophysiology and underlying mechanisms as that which most commonly develops in middle-aged adult humans. Amylase and lipase levels were characterized in 157 unrelated adult rhesus monkeys (Macaca mulatta); 38% developed T2DM while under study. In all monkeys, multivariable linear regression analysis revealed that amylase could be negatively predicted by % body fat (β -0.29; p = 0.002), age (β -0.27; p = 0.005), and HbA1c (β -0.18; p = 0.037). Amylase levels were positively predicted by lipase levels (β = 0.19; p = -0.024) in all NHPs included in the study. Amylase was significantly lower in NHPs with metabolic syndrome (p < 0.001), prediabetes (PreDM) (p < 0.001), and T2DM (p < 0.001) compared to metabolically normal adult NHPs. Lipase increased in NHPs with PreDM (p = 0.005) and T2DM (p = 0.04) compared to normal NHPs. This is the first longitudinal study of any species, including humans, to show the dynamics of amylase and lipase during the metabolic progression from normal to metabolic syndrome, to PreDM and then to overt T2DM. The extraordinary similarity between humans and monkeys in T2DM, in pancreatic pathophysiology and in metabolic functions give these findings high translational value.
Topics: Animals; Macaca mulatta; Diabetes Mellitus, Type 2; Lipase; Male; Metabolic Syndrome; Longitudinal Studies; Amylases; Female
PubMed: 38955666
DOI: 10.14814/phy2.16097 -
Journal of Pediatric Surgery Jun 2024Predicted 1-year survival of children with trisomy 18 (T18) has increased to 59.3%. We aimed to systematically review the characteristics, management, and outcomes of... (Review)
Review
INTRODUCTION
Predicted 1-year survival of children with trisomy 18 (T18) has increased to 59.3%. We aimed to systematically review the characteristics, management, and outcomes of children with T18 and hepatoblastoma.
METHODS
A systematic literature review of the PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases was performed according to the PRISMA 2020 statement (end-of-search date: 03/03/2024).
RESULTS
Fifty studies reporting on 70 patients were included. The median age at diagnosis was 11.5 months, 85.9% were female (n = 55/64), and 15.0% had mosaic T18 (n = 6/40). Diagnosis was made during symptom evaluation (most commonly hepatomegaly or abdominal mass) in 45.5% (n = 15/33), incidentally in 24.2% (n = 8/33), during surveillance with abdominal ultrasound in 18.2% (n = 6/33), and at autopsy in 12.1% (n = 4/33). The median tumor size was 6.4 cm, 33.3% had multiple tumors (n = 14/42), and metastasis was present in one patient (3.8%; n = 1/26). Neoadjuvant chemotherapy was administered in 42.6% (n = 26/61) and adjuvant chemotherapy in 31.6% (n = 18/57). Surgical treatment was performed in 64.2% (n = 43/67). Of the patients not diagnosed on autopsy, overall mortality was 35.5% (n = 22/62) over a median follow-up of 11.0 months. Among the 26 deceased patients (including those diagnosed on autopsy), the most common causes of death were cardiopulmonary disease (38.5%, n = 10/26) and tumor progression (30.8%, n = 8/26).
CONCLUSIONS
T18 does not preclude resection with curative intent for hepatoblastoma. Combination of surgery and chemotherapy should be considered in children on an individualized basis depending on tumor characteristics and underlying cardiopulmonary comorbidities. Locoregional modalities may have a role in the setting of severe comorbidities.
LEVEL OF EVIDENCE
Level IV evidence.
PubMed: 38955626
DOI: 10.1016/j.jpedsurg.2024.06.005 -
Medicina Clinica Jul 2024Parkinsonism in liver diseases or dysfunction, mainly including neurological manifestations in hereditary liver diseases and neurological complications of advanced liver... (Review)
Review
Parkinsonism in liver diseases or dysfunction, mainly including neurological manifestations in hereditary liver diseases and neurological complications of advanced liver diseases, occur in isolation or in combination with other movement disorders, and progress along disease course. Prominent akinetic-rigidity syndrome, various onset and progression, poor levodopa response and metabolism abnormalities reflected by serum biomarkers and neuroimaging, make this atypical parkinsonism recognizable and notable in clinical practice. Different susceptibility of brain areas, especially in basal ganglia, to manganese, iron, copper, ammonia overload, together with subsequent oxidative stress, neurotransmitter alterations, disturbed glia-neuron homeostasis and eventually neurotoxicity, contribute to parkinsonism under the circumstances of insufficient liver clearance ability. These mechanisms are interrelated and may interact collectively, adding to the complexity of clinical manifestations and treatment responses. This review summarizes shared clinical features of parkinsonism in liver diseases or dysfunction, depicts their underlying mechanisms and suggests practical flowchart for differential diagnosis.
PubMed: 38955605
DOI: 10.1016/j.medcli.2024.04.022 -
Neurospine Jun 2024Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and...
Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.
PubMed: 38955515
DOI: 10.14245/ns.2448140.070