Koefoedcleveland6448
OPO-initiated exceptions for kidney allocation are growing increasingly frequent and more concentrated at a few outlier centers. Increasing pressure to improve organ utilization risks increasing out-of-sequence allocations, potentially exacerbating disparities in access to transplantation.Ex vivo lung perfusion (EVLP) is a valuable method for expanding the lung donor pool. Its indications currently differ across centers. This national retrospective cohort study aimed to describe the profile of donors with lungs transplanted after EVLP and determine the effectiveness of EVLP on lung utilization. We included brain-dead donors with at least one lung offered between 2012 and 2019 in France. Lungs transplanted without or after EVLP were compared with those that were rejected. Donor group phenotypes were determined with multiple correspondence analysis (MCA). The association between donor factors and lung transplantation was assessed with a multivariable multinomial logistic regression. MCA revealed that donors whose lungs were transplanted after EVLP had profiles similar to the donors whose lungs were declined and quite different from those of donors with lungs transplanted without EVLP. Donor predictors of graft nonuse included age ≥50 years, smoking history, PaO2 /FiO2 ratio ≤300 mmHg, abnormal chest imaging, and purulent secretions. EVLP increased utilization of lungs from donors with a smoking history, PaO2 /FiO2 ratio ≤300 mmHg, and abnormal chest imaging.Pulsatillae Radix, the root of Pulsatilla chinensis (Bge.) Regel, is recorded in the Pharmacopoeia of the People's Republic of China and has been widely used for its pharmacological activities, such as anti-inflammatory, antioxidant, antibacterial, antitumor, and cardiovascular benefits. However, there are several look-alike species that can be marketed as Pulsatillae Radix. To distinguish P. chinensis (Bge.) Regel from its look-alikes, viz. Pulsatilla cernua (Thunb.) Bercht et Opiz., Pulsatilla dahurica (Fisch.) Spreng., Anemone tomeutosa (Maxim.) Pei., and Rhaponticum uniflorum (L.) DC, we used ultra high performance liquid chromatography with time-of-flight mass spectrometry combined with principal component analysis to compare their chemical compositions. Four ions, a (RT 8.98 min, m/z 1381.6671), b (RT 10.64 min, m/z 1219.6143), c (RT 11.52 min, m/z 1217.5978), and d (RT 13.6 min, m/z 749.4463), from P. chinensis (Bge.) Regel were identified as potential chemical markers to distinguish it from look-alike species using an unsupervised statistical model combined with orthogonal partial least-squares discriminant analysis. The results of this study provide an effective method for identifying and distinguishing P. Triparanol clinical trial chinensis (Bge.) Regel from similar plants.
Evaluation of the effects of the drugs used for iron supplementation on the peritoneal mesothelial cells.
Acute effects during18-h incubation of iron sucrose, ferric carboxymaltose, and iron isomaltoside in concentrations 1, 5, and 20 ug/dl on properties of the human peritoneal mesothelial cells in in vitro culture were evaluated, and their reversibility after the following culture for 14 days in the iron-free medium was studied.
All studied compounds reduced viability of mesothelial cells and proliferation rate and increased intracellular oxidative stress and iron content in the cytosol. Secretion of monocyte chemoattractant protein-1 was increased and tissue plasminogen activator (t-PA) decreased. After 14 days of culture in iron-free medium, reversibility of all these effects was observed.
Iron compounds impair the functional properties of mesothelial cells in a dose-dependent manner, but these effects are reversible after the following culture of the cells in an iron-free medium.
Iron compounds impair the functional properties of mesothelial cells in a dose-dependent manner, but these effects are reversible after the following culture of the cells in an iron-free medium.
Although combined therapy with peritoneal dialysis (PD) and hemodialysis (HD) is widespread in Japan, its clinical utility has been reported only in retrospective or before-and-after test lacking a control group.
We conducted a prospective, multicenter, observational cohort study of 176 incident PD patients and compared patient survival and changes in clinical parameters between patients on different dialysis modalities.
During a median follow-up of 41 months, 47 patients transferred to combined therapy and 35 patients transferred directly to HD. Patients transferred to combined therapy had a significantly better survival than those transferred directly to HD. However, we could not establish this difference in a multivariate analysis because only six patients died among these groups. The decreases in urea nitrogen and serum creatinine were more prominent among patients directly transferred to HD.
This is the first report revealing clinical feasibility of transfer to combined therapy for PD patients.
This is the first report revealing clinical feasibility of transfer to combined therapy for PD patients.A salting-out homogeneous liquid-liquid microextraction was proposed for the quantification of four azole drugs in human urine prior to high-performance liquid chromatography analysis. The procedure involved the mixing of the sample with acetonitrile in appropriate volumes followed by the addition of sodium sulfate solution in order to facilitate phase separation. The parameters influencing the extraction performance were studied and optimized using a two-step experimental design. The analytical procedure was thoroughly validated using the accuracy profiles as a graphical decision-making tool. The β-expectation tolerance intervals did not exceed the acceptance criteria of ±15% meaning that 95% of future results will be included in the defined bias limits. The limits of detection of the procedure were satisfactory, ranging between 0.01 and 0.03 μg/mL. The mean analytical bias in the spiking levels was satisfactory and ranged between -10.3 and 4.2% while the relative standard deviation was lower than 5.6%. Monte-Carlo simulations followed by capability analysis were employed to investigate the ruggedness of the sample preparation protocol. The developed method offers advantages compared to previously reported approaches for the same type of analysis including extraction efficiency and scaling down of the sample volume and extraction time.
The anti-von Willebrand factor (VWF) nanobody caplacizumab directly prevents the fatal microthrombi formation in immune-mediated thrombotic thrombocytopenic purpura (iTTP), thereby adding a new therapeutic principle to the treatment of this disorder. However, real-world treatment modalities beyond clinical trials remain heterogeneous.
Here, we describe the risks and benefits of an alternate-day dosing regimen for caplacizumab by thoroughly analyzing the timing and outcome of this approach in a retrospective cohort of 25 iTTP patients treated with caplacizumab at seven different medical centers in Austria and Germany between 2018 and 2021.
Alternate-day dosing of caplacizumab appeared feasible and led to persisting normal platelet counts in most patients. Five patients experienced iTTP exacerbations or relapses that led to the resumption of daily caplacizumab application. VWF activity was repeatedly measured in 16 of 25 patients and documented sufficient suppression by caplacizumab after 24 and 48h in line with published pharmacodynamics.
Extension of caplacizumab application intervals from daily to alternate-day dosing may be safely considered in selected patients after 3 to 4 weeks of daily treatment. Earlier modifications may be discussed in low-risk patients but require close monitoring for clinical and laboratory features of thrombotic microangiopathy.
Extension of caplacizumab application intervals from daily to alternate-day dosing may be safely considered in selected patients after 3 to 4 weeks of daily treatment. Earlier modifications may be discussed in low-risk patients but require close monitoring for clinical and laboratory features of thrombotic microangiopathy.Coronary artery perforation during percutaneous coronary intervention (PCI) is a rare but severe complication which has been associated with a high rate of major adverse outcomes and is potentially fatal. We report a case of a 70-year-old male who presented with an anterior ST-elevation myocardial infarction. Coronary angiogram revealed a proximal left anterior descending (LAD) artery occlusion. Successful PCI was performed with stenting of the LAD. However, subsequent attempts to retrieve a jailed diagonal branch inadvertently led to distal coronary perforation of the LAD. After failed attempts to tamponade the perforation with prolonged balloon inflation, this was successfully sealed with the MicroVascular Plug (Medtronic) system. To our knowledge, this is the first reported case of such an application in the coronary system. This may prove to be a viable alternative in closure of distal coronary perforations.
Microvesicles (MVs) are small double-membrane encapsulated particles shed from cells. Case-control studies have reported elevated plasma levels of platelet-derived MVs (PDMVs) in patients with venous thromboembolism (VTE). However, it is not known whether high PDMV levels is a risk factor or a consequence of the acute VTE event.
To investigate the association between PDMVs in plasma and risk of future incident VTE.
We performed a population-based nested case-control study with 314VTE cases and 705 age- and sex-matched controls (from The Tromsø Study) to investigate the association between the proportion of PDMVs (PDMVs%) in plasma and risk of future incident VTE. MVs isolated from plasma sampled at baseline (i.e., before VTE) were stained for platelet markers and analyzed by flow cytometry. PDMVs% were defined as the number of PDMVs divided by the total number of MVs. Odds ratios (ORs) with 95% confidence intervals (CI) for VTE risk were estimated across quartiles of PDMVs%.
Subjects with PDMVs% in the highest quartile had an OR for VTE of 1.78 (95% CI 1.21-2.64) and 1.99 (95% CI 1.24-3.26) for provoked VTE, compared to those in the lowest quartile. The association was moderately affected by multivariable adjustment for age, sex, body mass index, C-reactive protein, platelet count, and cancer. The OR for VTE was higher when the time between blood sampling and event was shorter.
Our results show that high proportions of PDMVs are associated with future risk of incident VTE and imply a role of platelet activation in the pathogenesis of VTE.
Our results show that high proportions of PDMVs are associated with future risk of incident VTE and imply a role of platelet activation in the pathogenesis of VTE.Qingfei Paidu Decoction is a Chinese medicine formula that has been proved effective in the treatment of coronavirus disease 2019. However, the comprehensive separation and characterization of Qingfei Paidu Decoction are of a great challenge due to the diversity of chemical components in a wide range of polarity. In this study, a triplex off-line two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry is developed for the analysis of Qingfei Paidu Decoction. One reversed-phase liquid chromatography×hydrophilic interaction liquid chromatography system and two reversed-phase liquid chromatography×reversed phase liquid chromatography systems were constructed to separate polar components and weak-polar components in Qingfei Paidu Decoction, respectively. Benefiting from the good orthogonality of two-dimensional liquid chromatography and high sensitivity of quadrupole time-of-flight MS, chemical components with different polarities and content were discovered. A total of 749 peaks were detected in positive and negative ionization mode and presented as a four-dimensional data plot.