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Childhood IgA nephropathy (cIgAN) is one of the most common primary glomerulonephritides with the potential to evolve to kidney failure. IgAN is an autoimmune disease involving 3 key factors galactose-deficient IgA1 (Gd-IgA1), anti-IgA1 autoantibodies, and soluble (s)CD89 IgA Fc receptor. These molecules and immune complexes have been described recently as potential biomarkers of disease progression in childhood IgAN but their evolution in time under immunosuppressive treatment remains unknown.
We performed a prospective study of two proliferative cIgAN patients by sequentially biomonitoring immune IgA complexes (sCD89-IgA, IgG-IgA), sCD89, and Gd-IgA1 and correlating them with clinical and histological outcome after treatment.
After patient 1's treatment, a decrease in sCD89-IgA, IgG-IgA, and free sCD89 was linked to a decrease in proteinuria whereas eGFR (estimated glomerular filtration rate) and Gd-IgA1 levels remained stable. Patient 1 received tacrolimus and monthly intramuscular steroid injectionsrkers could represent useful tools to evaluate kidney injury without repeat kidney biopsies.
In conclusion, sequential biomonitoring of Gd-IgA1, IgA-immune complexes, and sCD89 in cIgAN was found to be valuable, by correlating with clinical features and glomerular proliferative lesions in cIgAN. These biomarkers could represent useful tools to evaluate kidney injury without repeat kidney biopsies.
Pneumoperitoneum is a common complication of percutaneous endoscopic gastrostomy (PEG). We report a case of circulatory and respiratory depression due to pneumoperitoneum caused by PEG dislodgement during endoscopic submucosal dissection (ESD) surgery.
A 46-year-old man with PEG for dysphagia underwent ESD for esophageal cancer under general anesthesia. The patient developed a gradual increase in peak inspiratory pressure, followed by a decrease in peripheral oxygen saturation (SpO
) and blood pressure, as well as an increase in heart rate (HR) during endoscopic submucosal ESD for esophageal cancer. We suspected mediastinal emphysema due to esophageal perforation, but the surgery was successfully completed. Postoperative computed tomography (CT) revealed that the abdominal and gastric walls, which had been fixed by PEG, were detached, resulting in a large amount of intra-abdominal gas and mediastinal emphysema.
ESD in patients with PEG should be performed carefully because of the possibility of intraoperative PEG dislodgement and pneumoperitoneum caused by insufflation gas leakage.
ESD in patients with PEG should be performed carefully because of the possibility of intraoperative PEG dislodgement and pneumoperitoneum caused by insufflation gas leakage.Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases in the global swine industry. Gamcemetinib A rapid and sensitive on-site detection method for PRRS virus (PRRSV) is critically important for diagnosing PRRS. In this study, we established a method that combines reverse transcription recombinase polymerase amplification (RT-RPA) with a lateral flow dipstick (LFD) for detecting North American PRRSV (PRRSV-2). The primers and probe were designed based on the conserved region of all complete PRRSV-2 genomic sequences available in China (n = 512) from 1996 to 2020. The detection limit of the assay was 5.6 × 10-1 median tissue culture infection dose (TCID50) per reaction within 30 min at 42 °C, which was more sensitive than that of reverse transcription polymerase chain reaction (RT-PCR) (5.6 TCID50 per reaction). The assay was highly specific for the epidemic lineages of PRRSV-2 in China and did not cross-react with pseudorabies virus, porcine circovirus 2, classical swine fever virus, or porcine epidemic diarrhea virus. The assay performance was evaluated by testing 179 samples and comparing the results with those of quantitative RT-PCR (RT-qPCR). The results showed that the detection coincidence rate of RT-RPA and RT-qPCR was 100% when the cycle threshold values of RT-qPCR were less then 32. The assay provides a new alternative for simple and reliable detection of PRRSV-2 and has great potential for application in the field.Fusogenic aquareoviruses can induce host cell-cell fusion, forming syncytia via a fusion-associated transmembrane protein. However, there have been very few reports on non-fusogenic aquareoviruses encoding a membrane-associated protein. Previously, sequence-based analysis has indicated that grass carp reovirus strain 104 (GCRV-104), a non-fusogenic aquareovirus, encodes the proteins VP8 (nt 36-263) and VP15 (nt 400-822) in its genome segment S11. Here, we employed a liquid chromatography-tandem mass spectrometry assay to experimentally annotate small coding genes in the GCRV-104 genome and confirmed that segment S11 indeed functions as bicistronic mRNA. Notably, some additional polypeptides were identified that are encoded upstream of the VP15 open reading frame (ORF), which suggests that the virus uses a novel ORF with a non-AUG initiator codon, tentatively named VP15L (nt 274-822), which is longer than the previous putative VP15 ORF. Furthermore, a transmembrane domain was identified at the N-terminus of VP15L, but its function is unclear. Thus, the aquareovirus GCRV-104 potentially encodes a transmembrane protein, which opens a new perspective on the properties of viral proteins and the pathogenesis of this non-fusogenic reovirus.
The importance of sagittal alignment restoration in early onset scoliosis (EOS) management has rarely been investigated to date. The aim was to report the influence of magnetically controlled growing rods (MCGR) insertion on the sagittal alignment of EOS patients.
All consecutive ambulatory patients operated with MCGR rods between 2011 and 2018 were retrospectively included in four institutions. Standing biplanar radiographs were performed preoperatively, in the early postoperative period and at latest follow-up. Global and local sagittal parameters, spinal global shape and harmony were investigated.
A total of 37 ambulatory EOS patients were included (mean age at surgery 8.5 (± 2) years). 70% had a balanced construct postoperatively. Both MaxTK (- 17°, p = 0.02) and MaxLL (- 15°, p = 0.001) were significantly reduced, particularly at the instrumented levels. The number of vertebrae included in the lumbar lordosis significantly increased (+ 2 levels, p = 0.02), as well as the thoraco-lumbar inflexion point (+ 2 levels, p < 0.001) and the kyphosis apex (+ 1 level, p < 0.001). Overall mechanical failure rate was 40.5%, and radiological PJK was observed in 43% of the patients, with 11 remaining asymptomatic. Patients with initial hyperkyphosis (> 50°) developed more complications (62% vs. 28%, p = 0.04).
MCGR insertion flattened the spine in EOS, at both instrumented and non-instrumented levels. Overall spinal harmony was modified, with a cranial shift of the thoraco-lumbar inflexion point and the thoracic kyphosis apex, associated with a lengthening of the lumbar lordosis. The rate of complication remained high, some explanations being found in the radiological changes reported such as the preoperative location of the TK apex.
IV.
IV.Triple-negative breast cancer (TNBC) has an aggressive biological behavior and poor outcome. Our published study showed that PAI-1 could induce the migration and metastasis of TNBC cells. link2 However, the underlying mechanism by which PAI-1 regulates TNBC metastasis has not been addressed. Here, we demonstrated that PAI-1 is high expressed in TNBC and promotes TNBC cells tumorigenesis. Using microarray analysis of lncRNA expression profiles, we identified a lncRNA SOX2-OT, which is induced by PAI-1 and could function as an oncogenic lncRNA in TNBC. link3 Mechanistic analysis demonstrated that SOX2-OT acts as a molecular sponge for miR-942-5p to regulate the expression of PIK3CA, ultimately leading to activating PI3K/Akt signaling pathway and promoting TNBC metastasis. Taken together, our findings suggest that SOX2-OT regulates PAI-1-induced TNBC cell metastasis through miR-942-5p/PIK3CA signaling and illustrate the great potential of developing new SOX2-OT-targeting therapy for TNBC patients.
High cancer risks, as applicable to BRCA1 and BRCA2 pathogenic variant (PV) carriers, can induce significant cancer concerns. We examined the degree of cancer worry and the course of this worry among BRCA1/2-PV carriers undergoing surgery to prevent ovarian cancer, and identified factors associated with high cancer worry.
Cancer worry was evaluated as part of the multicentre, prospective TUBA-study (NCT02321228) in which BRCA1/2-PV carriers choose either novel risk-reducing salpingectomy with delayed oophorectomy or standard risk-reducing salpingo-oophorectomy. The Cancer Worry Scale was obtained before and 3 and 12months after surgery. Cancer worry patterns were analysed using latent class growth analysis and associated factors were identified with regression analysis.
Of all 577 BRCA1/2-PV carriers, 320 (57%) had high (≥ 14) cancer worry pre-surgery, and 54% had lower worry 12months post-surgery than pre-surgery. Based on patterns over time, BRCA1/2-PV carriers could be classified into three groups persistently low cancer worry (56%), persistently high cancer worry (6%), and fluctuating, mostly declining, cancer worry (37%). Factors associated with persistently high cancer concerns were age below 35 (BRCA1) or 40 (BRCA2), unemployment, previous breast cancer, lower education and a more recent BRCA1/2-PV diagnosis.
Some degree of cancer worry is considered normal, and most BRCA1/2-PV carriers have declining cancer worry after gynaecological risk-reducing surgery. However, a subset of these BRCA1/2-PV carriers has persisting major cancer concerns up to 1year after surgery. They should be identified and potentially offered additional support.
The TUBA-study is registered at ClinicalTrials.gov since December 11th, 2014. Registration number NCT02321228.
The TUBA-study is registered at ClinicalTrials.gov since December 11th, 2014. Registration number NCT02321228.
Cancer patients' sources of distress are often unaddressed, and patient-reported distress data could be utilized to identify those with unmet and impending care needs. We explored the association between moderate/severe distress and healthcare utilization in a large sample of non-small cell lung cancer (NSCLC) and non-colorectal gastrointestinal cancer patients.
Adult patients treated between July 2013 and March 2019. Data from the NCCN Distress Thermometer (DT) and the accompanying "Problem List" were extracted from the EHR. A DT score of ≥ 4 indicates "actionable distress." Statistical analysis was performed using descriptive analysis for patient characteristics, clinical outcomes, and sources of distress. Generalized linear mixed models were fit to determine the relationship between distress and healthcare utilization (hospitalization, emergency department (ED) visit, or both).
The ten most frequently reported problems were from the Physical and Emotional domains of the Problem List. Distress was mostly related to physical symptoms (pain, fatigue) and emotional issues (worry, fears, sadness, nervousness). Patients with actionable distress generally reported more problems across all their visits. Actionable distress was associated with higher odds of the composite outcome measure of hospitalization or visiting the ED, within both the next 3months (OR = 1.37; 95% CI = 1.19, 1.58; p < 0.001) and 6months (OR = 1.19; 95% CI = 1.03, 1.37; p = 0.019).
Patients with significant distress had marked utilization of ED and inpatient services. DT scores are a source of untapped data in the EHR that can highlight patients in need of intervention, including palliative care and cancer support services.
Patients with significant distress had marked utilization of ED and inpatient services. DT scores are a source of untapped data in the EHR that can highlight patients in need of intervention, including palliative care and cancer support services.
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