Objectives:To identify the key points for improving severe maternal morbidity by analyzing pregnancy-related ICU admissions in Beijing.Design:This was a retrospective, multicenter cohort study.Setting:Three ICUs in tertiary hospitals in Beijing.Patients:A total of 491 severe maternal cases in any trimester of pregnancy or within 42 days of delivery were reviewed between January 1, 2008, and December 31, 2016.Interventions:None.Measurements and Main Results:Among 491 obstetric ICU admissions (median Sequential Organ Failure Assessment score, 2) out of 87,850 hospital deliveries (a frequency of 5.6 admissions per 1,000 deliveries), the leading diagnoses were postpartum hemorrhage (170; 34.62%), hypertensive disorders of pregnancy (156; 31.77%), and cardio-cerebrovascular diseases (78; 15.9%). Comparing 2008–2011 to 2012–2016, the rates of maternal mortality (2.5% vs 1.9%; p = 0.991) and fetal loss (8.5% vs 8.6%; p = 0.977) did not decrease significantly, whereas the rates of ICU admission (3.05% vs 7.85%; p trends < 0.001) and postpartum hemorrhage (23% vs 38.5%; p = 0.002) increased. Hypertensive disorder (150/156; 96.2% transferred to the ICU postpartum, 24/28 women with fetal loss transferred from lower-level hospitals) was an independent maternal factor associated with fetal loss, and infections were the leading cause of maternal death (6/10) in the ICU.Conclusions:Our study highlights the increasing rate of intensive care admissions for postpartum hemorrhage. Improving prenatal care quality for pregnancy-induced hypertension and sepsis at lower-level hospitals may improve maternal and fetal outcomes. Specifically, providing more effective regional cooperation before transfer and shifting patients who require continuous surveillance but not necessarily intensive care to a transitional ward in a tertiary hospital would provide more ICU beds for more prenatal intensive care for the most complex medical conditions.
Background Acute kidney injury (AKI) is a common clinical disease with complex pathophysiology and limited therapeutic choices. This prompts the need for novel therapy targeting multiple aspects of this disease. Human amnion epithelial cell (hAEC) is an ideal stem cell source. Increasing evidence suggests that exosomes may act as critical cell–cell communicators. Accordingly, we assessed the therapeutic potential of hAECs and their derived exosomes (hAECs-EXO) in ischemia reperfusion mouse model of AKI and explored the underlying mechanisms. Methods The hAECs were primary cultured, and hAECs-EXO were isolated and characterized. An ischemic-reperfusion injury-induced AKI (IRI-AKI) mouse model was established to mimic clinical ischemic kidney injury with different disease severity. Mouse blood creatinine level was used to assess renal function, and kidney specimens were processed to detect cell proliferation, apoptosis, and capillary density. Macrophage infiltration was analyzed by flow cytometry. hAEC-derived exosomes (hAECs-EXO) were used to treat hypoxia-reoxygenation (H/R) injured HK-2 cells and mouse bone marrow-derived macrophages to evaluate their protective effect in vitro. Furthermore, hAECs-EXO were subjected to liquid chromatography-tandem mass spectrometry for proteomic profiling. Results We found that systematically administered hAECs could improve mortality and renal function in IRI-AKI mice, decrease the number of apoptotic cells, prevent peritubular capillary loss, and modulate kidney local immune response. However, hAECs showed very low kidney tissue integration. Exosomes isolated from hAECs recapitulated the renal protective effects of their source cells. In vitro, hAECs-EXO protected HK-2 cells from H/R injury-induced apoptosis and promoted bone marrow-derived macrophage polarization toward M2 phenotype. Proteomic analysis on hAECs-EXO revealed proteins involved in extracellular matrix organization, growth factor signaling pathways, cytokine production, and immunomodulation. These findings demonstrated that paracrine of exosomes might be the key mechanism of hAECs in alleviating renal ischemia reperfusion injury. Conclusions We reported hAECs could improve survival and ameliorate renal injury in mice with IRI-AKI. The anti-apoptotic, pro-angiogenetic, and immunomodulatory capabilities of hAECs are at least partially, through paracrine pathways. hAECs-EXO might be a promising clinical therapeutic tool, overcoming the weaknesses and risks associated with the use of native stem cells, for patients with AKI.
Background The optimal use of vancomycin in the elderly requires information about the drug’s pharmacokinetics and the influence of various factors on the drug’s disposition. However, because of sampling restrictions, it is often difficult to perform traditional pharmacokinetic studies in elderly patients. Objective This study was conducted to estimate the population pharmacokinetics of vancomycin in Chinese geriatric patients (age ≥ 65 years) with pulmonary infections and to explore the clinical application of this information for vancomycin dose individualization. Methods The steady-state trough concentrations were retrospectively collected from January 2011 to December 2016 and were analyzed using the nonlinear mixed-effect model software. The final model was evaluated using the bootstrap method, goodness-of-fit plots and the normalized prediction distribution error method. Main Outcome Measure Model parameters and prediction error. Results A total of 125 steady-state trough concentrations from 70 patients were retrospectively collected. A one-compartment model was established. The final model was depicted as clearance (CL) [L/h] = 2.45 × (CL CR /56.28) × 0.542; volume of distribution ( V d ) [L] = 154. The creatinine clearance (CL CR ) was identified as the most significant covariate in the final model. The typical values of CL and V d in the final model were 2.45 L/h and 154 L, respectively. Model validation outcomes showed that the final model was stable and had satisfactory prediction performance. Conclusion A population pharmacokinetic model was established to estimate the pharmacokinetics characteristics of Chinese geriatric patients with pulmonary infections, and this model can be used to develop an initial vancomycin dosing regimen for geriatric patients.
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