In the present study, sympathetic skin response (SSR) characteristics were explored in children with Guillain-Barré syndrome (GBS) and the value of early diagnosis and prognostic evaluation in GBS complicated by autonomic dysfunction (AD) was evaluated.A total of 25 children with GBS and 30 healthy controls (HCs) were enrolled in this prospective study. SSR findings for the two groups were compared. SSR and nerve conduction study (NCS) results were compared among patients with GBS, and differences in clinical characteristics between the groups with abnormal and normal SSR were analyzed.Within the GBS group, six patients (24%) required mechanical ventilation, 17 patients (66.7%) had AD, 18 patients (72%) had an abnormal SSR, and 13 patients (52%) had AD combined with SSR abnormalities. There was a statistically significant difference in SSR latency in the lower limbs between the GBS group and HCs (P < 0.05). There was no statistically significant difference between SSR and NCS results in the acute phase of GBS (P > 0.05), and there was no significant difference in the rate of AD or in Hughes functional grade at nadir between the groups with abnormal and normal SSR (P>0.05). However, there was a statistically significant difference between the results of SSR and NCS tests during the recovery phase (P = 0.003). Abnormal SSR mainly occurred in cases of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype. In addition, SSR was abnormal in all pediatric GBS patients with poor prognosis 1 month after onset of symptoms.Two-thirds of the children with GBS have AD. SSR could be used for early diagnosis and follow-up of GBS and may also be helpful in evaluating disease severity and short-term prognosis.
Abstract Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. We reported a severe uremic calciphylaxis patient with progressive skin ischemia, large areas of painful malodorous ulcers and mummified legs. Because of her rapid progression and refractory to conventional therapy, human amnion-derived mesenchymal stem cells (hAMSCs) treatment was approved. Establishment and release inspection of hAMSCs, efficacy and safety assessment including cytokines secretory ability, immunocompetence, tumorigenicity and genetics analysis in vitro were introduced. We further performed acute and long-term hAMSC toxity evaluations in C57BL/6 mice/rats, abnormal immune response tests in C57BL/6 mice and tumorigenic tests in the neonatal NU nude mice. After pre-clinical research, she was treated by hAMSCs with intravenous and local intramuscular injection and external supernatants application to her ulcers. When followed up to 15 months, her blood-based markers of bone and mineral metabolism were improved, with regeneration of skin soft tissue and a more favorable profile of peripheral blood mononuclear cells. Skin biopsy after 1 month treatment showed vascular regeneration with mature non-calcified vessels within dermis and 20 months later re-epithelialization restored the integrity of damaged site. No infusion or local treatment related adverse events occurred. To the best of our knowledge, this is the first evidence for the clinical use of hAMSCs. These findings suggest hAMSCs warrant further investigation as a potential regenerative treatment for uremic calciphylaxis with effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, anti-inflammatory and immune modulation, multi-differentiation, re-epithelialization and restorage of integrity.
Importance Despite the expansion of published electronic alerts for acute kidney injury (AKI), there are still concerns regarding their effect on the clinical outcomes of patients. Objective To evaluate the effect of the AKI alert combined with a care bundle on the care and clinical outcomes of patients with hospital-acquired AKI. Design, Setting, and Participants This single-center, double-blind, parallel-group randomized clinical trial was conducted in a tertiary teaching hospital in Nanjing, China, from August 1, 2019, to December 31, 2021. The inclusion criteria were inpatient adults aged 18 years or older with AKI, which was defined using the Kidney Disease: Improving Global Outcomes creatinine criteria. Participants were randomized 1:1 to either the alert group or the usual care group, which were stratified by medical vs surgical ward and by intensive care unit (ICU) vs non-ICU setting. Analyses were conducted on the modified intention-to-treat population. Interventions A programmatic AKI alert system generated randomization automatically and sent messages to the mobile telephones of clinicians (alert group) or did not send messages (usual care group). A care bundle accompanied the AKI alert and consisted of general, nonindividualized, and nonmandatory AKI management measures. Main Outcomes and Measures The primary outcome was maximum change in estimated glomerular filtration rate (eGFR) within 7 days after randomization. Secondary patient-centered outcomes included death, dialysis, AKI progression, and AKI recovery. Care-centered outcomes included diagnostic and therapeutic interventions for AKI. Results A total of 2208 patients (median [IQR] age, 65 [54-72] years; 1560 males [70.7%]) were randomized to the alert group (n = 1123) or the usual care group (n = 1085) and analyzed. Within 7 days of randomization, median (IQR) maximum absolute changes in eGFR were 3.7 (−6.4 to 19.3) mL/min/1.73 m 2 in the alert group and 2.9 (−9.2 to 16.9) mL/min/1.73 m 2 in the usual care group ( P = .24). This result was robust in all subgroups in an exploratory analysis. For care-centered outcomes, patients in the alert group had more intravenous fluids (927 [82.6%] vs 670 [61.8%]; P &lt; .001), less exposure to nonsteroidal anti-inflammatory drugs (56 [5.0%] vs 119 [11.0%]; P &lt; .001), and more AKI documentation at discharge (560 [49.9%] vs 296 [27.3%]; P &lt; .001) than patients in the usual care group. No differences were observed in patient-centered secondary outcomes between the 2 groups. Conclusions and Relevance Results of this randomized clinical trial showed that the electronic AKI alert did not improve kidney function or other patient-centered outcomes but changed patient care behaviors. The findings warrant the use of a combination of high-quality interventions and AKI alert in future clinical practice. Trial Registration ClinicalTrials.gov Identifier: NCT03736304
Abstract Background Calciphylaxis, which mostly affects individuals with end-stage kidney disease (ESKD), is also known as calcific uremic arteriolopathy (CUA). It is a rare and fatal disease that manifests with calcification and thrombosis of microvessels, ischemia, and necrosis in skin tissues(ORPHA:280062). Histopathological features of extracutaneous tissues of CUA patients undergoing human amnion–derived mesenchymal stem cell (hAMSC) treatment remain unknown. Methods A female CUA patient, treated with hAMSCs for 20 months, passed away due to stroke. Histopathological features of her extracutaneous tissues were compared with those of ESKD patients (n = 7). Raman spectroscopy was applied to identify the composition of calcifications. The distribution of hAMSCs, derived from the amnion of a male fetus, in tissues of the CUA patient was determined by detecting the Y chromosome using reverse-transcription–polymerase chain reaction. Results Microvessel lesions were more prevalent in the extracutaneous tissues of the CUA patient than in those of ESKD patients, although the regenerated skin showed normal histological characteristics. The CUA patient exhibited calcifications of microvessel media, including the microvessels in the lungs, kidneys, spleen, pancreas, and uterus. Her mitral valve and kidney displayed severe calcification, identified as calcium phosphate with some calcium carbonate. hAMSCs were not detected in the tissues of the CUA patient. Conclusion Under the treatment strategy with hAMSCs, based on the effects of skin regeneration, microvascular lesions in the extracutaneous tissues of the CUA patient were more severe than those in ESKD patients. CUA should be considered a systemic disease when identifying treatment targets.
Mortality rates from various cancer types are higher in patients with hyperglycaemia-associated pathologies. Among antineoplastics for treating pancreatic carcinoma, doxorubicin was found to be top of the list for inducing hyperglycaemia-related adverse drug reactions.Individual case safety reports of doxorubicin-induced hyperglycaemia-related adverse drug reactions (HG-ADRs) submitted during the period 2000-2017 were extracted from VigiBase®. Factors influencing outcome seriousness in these cases were analyzed using bivariate correlation and logistical regression. Age was stratified into five groups.Among the 558 cases with high blood glucose included in this study, with an average patient age of 55.9 ± 14.3 years, 71.1% had serious outcomes and 10.9% died. Three factors-died, age, and gender-were all found to be significantly correlated with outcome seriousness (P < 0.01), while five factors-year reported, ADR duration, latency, treatment duration, and dosage-showed no correlation with outcome seriousness (P > 0.05). Identical conclusions were reached upon analyzing only the cases that did not involve corticosteroid use.Age and gender are risk factors for doxorubicin-induced serious HG-ADRs; males and older patients are more likely to suffer a serious outcome following such a reaction.
Seed germination is a physiological process regulated by multiple factors. Abscisic acid (ABA) can inhibit seed germination to improve seedling survival under conditions of abiotic stress, and this process is often regulated by light signals. Constitutive Photomorphogenic 1 (COP1) is an upstream core repressor of light signals, and is involved in several ABA responses. Here, we demonstrate that COP1 is a negative regulator of the ABA-mediated inhibition of seed germination. Disruption of COP1 enhanced Arabidopsis seed sensitivity to ABA and increased ROS levels. In seeds, ABA induced the translocation of COP1 to the cytoplasm, resulting in enhanced ABA-induced ROS levels. Genetic evidence indicated that HY5 and ABI5 act downstream of COP1 in the ABA-mediated inhibition of seed germination. ABA-induced COP1 cytoplasmic localization increased HY5 and ABI5 protein levels in the nucleus, leading to increased expression of ABI5 target genes and ROS levels in seeds. Together, our results reveal that ABA-induced cytoplasmic translocation of COP1 activates the HY5-ABI5 pathway to promote the expression of ABA-responsive genes and the accumulation of ROS during ABA-mediated inhibition of seed germination. These findings enhance the role of COP1 in the ABA signal transduction pathway.
Introduction: Acute kidney injury has been identified as a common complication of cardiac surgery. To date, the effect of the time interval from coronary angiography to cardiac surgery on postoperative acute kidney injury is still controversial. The aim of this study was to investigate the relationship between the timing of coronary angiography and cardiac surgery associated acute kidney injury. Methods: Eight hundred thirteen patients who underwent coronary angiography and cardiac surgery successively from January 2017 to December 2018 were included in this retrospective cohort study. We applied multivariate logistic regression, propensity score analysis, and subgroup analysis to evaluate the association between the time interval and postoperative acute kidney injury incidence and prognosis. Meta-analysis was conducted to verify the results. Results: The overall incidence of the cardiac surgery associated acute kidney injury was 28.8%. Age (OR = 1.046, 95%CI: 1.017–1.075), cardiopulmonary bypass (OR = 3.439, 95%CI: 1.316–8.986) and diabetes (OR = 2.522, 95%CI: 1.439–4.417) were found to be independent risk factors of postoperative acute kidney injury in multivariate logistic regression and propensity score analysis. Undergoing cardiac surgery within 7 days after coronary angiography was not associated with increased incidence of postoperative acute kidney injury or worse prognosis. Meta-analysis obtained consistent results. Conclusions: The time interval shorter than 7 days had no influence on cardiac surgery associated acute kidney injury incidence and prognosis. The decision of delaying the surgery should be made after comprehensive evaluation of the patient.
To explore the clinicopathological features of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (anti-GBM-GN) and the prognostic values of clinical and laboratory indicators at diagnosis on renal and patient survival.A total of 76 patients (34 males and 42 females) with anti-GBM-GN who were hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2010 and June 2021 were included in this study. The baseline clinical features, histopathological data from renal biopsies, and predictors of renal and patient survival were retrospectively analyzed.Among the 76 patients, the median serum creatinine at diagnosis was 618.0 (350.98, 888.25) μmol/L and the median estimated glomerular filtration rate (eGFR) was 6.62 (4.39, 14.41) mL/min. Of these 76 patients, 55 (72.4%) received initial kidney replacement therapy (KRT) and 39 (51.3%) received plasma exchange or double-filtered plasmapheresis (DFPP). During a median follow-up duration of 28.5 (6.0, 71.8) months, 53 (69.7%) patients progressed to kidney failure with replacement therapy (KFRT) and received maintenance dialysis. Initial KRT (HR = 3.48, 95% CI = 1.22-9.97, p = 0.020) was a significant risk factor for renal survival. During the follow-up, 49 (64.5%) of 76 patients survived. Age (≥60 years, HR = 4.13, 95% CI = 1.65-10.38, p = 0.003) and initial KRT (HR = 2.87, 95% CI = 1.01-8.14, p = 0.047) were predictive of patient survival.Among patients with anti-GBM-GN, initial KRT at presentation was predictive of KFRT while older age and initial KRT were associated with higher all-cause mortality.
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