Obstetric outcomes in pregnant COVID-19 women: the imbalance of von Willebrand factor and ADAMTS13 axis

Background: Thrombotic microangiopathy has been invoked as one of the most important mechanisms of damage in COVID-19 patients. Protease ADAMTS13 is a marker of microangiopathy responsible for controlling von Willebrand multimers size. Von Willebrand factor/ADAMTS13 ratio has been found impaired in COVID-19 patients outside pregnancy. Methods: We prospectively investigated 90 pregnant women admitted to two tertiary academic hospitals in Italy with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Demographic, clinical information and routine laboratory data were collected at the hospital admission and until discharge. We investigated whether vonWillebrand /ADAMTS13 axis imbalance is a predictor of adverse outcomes. Logistic regression analysis, which controlled for potential confounders, was performed to evaluate the association between laboratory parameters and clinical outcomes. Results: Most women (55.6%) were parae, with median gestational age at admission of 39 weeks. At hospital admission, 63.3% were asymptomatic for COVID-19 and 24.4% showed more than one sign or symptom of infection. Nulliparae with group O showed Willebrand / ADA MTS-13 ratios significantly lower than non-O, whereas in multiparae this difference was not observed. Logistic regression showed that ratio von Willebrand to ADAMTS13 was significantly and independently associated with preterm delivery (OR 1.9, 95%CI 1.1–3.5). Conclusion: This study shows an imbalance of vonWillebrand /ADAMTS13 axis in pregnant women with COVID-19, leading to a significantly higher and independent risk of preterm delivery. Monitoring these biomarkers might support decision making process to manage and follow-up pregnancies in this setting

Synthesis of cholic acid-terminated dendritic lysine-block-poly(ethylene glycol)­-block-dendritic lysine for paclitaxel delivery

Paclitaxel, a chemotherapeutic drug used to inhibit mitosis in cancer cells, requires the use of the solubilizer Cremophor EL due to its poor water solubility. However, Cremophor EL is associated with adverse reactions following chemotherapy. This study aimed to synthesize an alternative solubilizing agent for use with paclitaxel and similar drugs.Two generations of dendritic lysine were coupled onto both ends of PEG-4000 via fluorenylmethyloxycarbonyl (FMOC) chemistry with dicyclohexylcarbodiimide (DCC)-mediated condensation. Cholic acid was attached to the terminal amino groups through the use of DCC/n-hydroxysuccinimide. Synthesis steps were monitored and confirmed by electrospray ionization mass spectroscopy. Paclitaxel loading was induced via the solvent evaporation method. The paclitaxel loading capacity of the synthesized polymer was analyzed by high-performance liquid chromatography. In vitro cytotoxicity assays of the paclitaxel-loaded polymer and polymer alone as compared to commercial paclitaxel formulation were performed on human breast adenocarcinoma (MCF-7) cell line.Masses corresponding to completely-synthesized dendritic polymers were found in the mass spectra. The polymer was able to load up to 47.70% of its mass in paclitaxel. The IC50 values (in ug/ul) of the paclitaxel-loaded and unloaded polymer were 26.22 and 50.62, respectively. The results suggest that the synthesized polymer is a viable solubilizing agent for delivery of paclitaxel. Additional studies are required to assess its safety and stability

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

Molecular diagnostic methods based on the detection of mutations conferring drug resistance are promising technologies for rapidly detecting multidrug-/extensively drug-resistant tuberculosis (M/XDR TB), but large studies of mutations as markers of resistance are rare. The Global Consortium for Drug-Resistant TB Diagnostics analyzed 417 Mycobacterium tuberculosis isolates from multinational sites with a high prevalence of drug resistance to determine the sensitivities and specificities of mutations associated with M/XDR TB to inform the development of rapid diagnostic methods. We collected M/XDR TB isolates from regions of high TB burden in India, Moldova, the Philippines, and South Africa. The isolates underwent standardized phenotypic drug susceptibility testing (DST) to isoniazid (INH), rifampin (RIF), moxifloxacin (MOX), ofloxacin (OFX), amikacin (AMK), kanamycin (KAN), and capreomycin (CAP) using MGIT 960 and WHO-recommended critical concentrations. Eight genes (katG, inhA, rpoB, gyrA, gyrB, rrs, eis, and tlyA) were sequenced using Sanger sequencing. Three hundred seventy isolates were INH(r), 356 were RIF(r), 292 were MOX(r)/OFX(r), 230 were AMK(r), 219 were CAP(r), and 286 were KAN(r). Four single nucleotide polymorphisms (SNPs) in katG/inhA had a combined sensitivity of 96% and specificities of 97 to 100% for the detection of INH(r). Eleven SNPs in rpoB had a combined sensitivity of 98% for RIF(r). Eight SNPs in gyrA codons 88 to 94 had sensitivities of 90% for MOX(r)/OFX(r). The rrs 1401/1484 SNPs had 89 to 90% sensitivity for detecting AMK(r)/CAP(r) but 71% sensitivity for KAN(r). Adding eis promoter SNPs increased the sensitivity to 93% for detecting AMK(r) and to 91% for detecting KAN(r). Approximately 30 SNPs in six genes predicted clinically relevant XDR-TB phenotypes with 90 to 98% sensitivity and almost 100% specificity