ABSTRACT
Introduction: Preexisting anticoagulation is common among geriatric trauma patients. Geriatric trauma patients have a higher risk of mortality compared to younger patients. We sought to evaluate the association of preexisting anticoagulation with mortality in a group of geriatric trauma patients. Methods: A retrospective review of geriatric trauma patients was conducted for those admitted to a Level 1 trauma center from January 2018 to December 2020. Vital signs, demographics, injury characteristics, laboratory data, and mortality were all collected. Multivariable logistic regression analysis was performed for the association of preexisting anticoagulation and a primary endpoint of all-cause mortality. These groups were controlled for preexisting comorbidities, injury severity scores, and systolic blood pressure in the emergency department. Results: Four thousand four hundred thirty-two geriatric patients were admitted during the study period. This cohort was made up of 36.9% men and 63.1% women. Three thousand eight hundred fifty-nine (87.2%) were white; the average age was 81±8.5 years, and the median injury severity score (ISS) was 5. The mean systolic blood pressure was 150±32 mmHg, mean heart rate was 81±16 bpm, mean lactate was 2.3±1.3, mean hematocrit was 37.3±8.8, and mean international normalized ratio (INR) was 1.7±10.3. One thousand five hundred ninety-two (35.9%) patients were on anticoagulation (AC) upon presentation. One hundred and sixty-five (3.7%) mortalities were recorded. Multivariable logistic regression analysis results show that preexisting anticoagulation [ odds ratio (OR) 1.92, 95% CI 1.36-2.72] was independently predictive of death. The analysis was adjusted for systolic BP in the emergency department less than90 mmHg (OR 5.55, 95% CI 2.83-10.9), having more than 1 comorbidity (OR 2.30, 95% CI 1.57-3.38) and ISS (OR 1.13, 95% CI 1.10-1.15). Conclusion: Our study indicates that preexisting anticoagulation is associated with mortality among geriatric trauma patients.
ABSTRACT
Nonminimum carbonic acid clusters provide excitation energies and oscillator strengths in line with observed ice-phase UV absorptions better than traditional optimized minima. This equation-of-motion coupled cluster quantum chemical analysis on carbonic acid monomers and dimers shows that shifts to the dihedral angle for the internal heavy atoms in the monomer produce UV electronic excitations close to 200 nm with oscillator strengths that would produce observable features. This τ(OCOO) dihedral is actually a relatively floppy motion unlike what is often expected for sp2 carbons and can be distorted by 30° away from equilibrium for an energy cost of only 11 kcal/mol. As this dihedral decreases beyond 30°, the excitation energies decrease further. The oscillator strengths do, as well, but only to a point. Hence, the lower-energy distortions of τ(OCOO) are sufficient to produce structures that exhibit excitation energies and oscillator strengths that would red-shift observed spectra of carbonic acid ices away from the highest UV absorption feature at 139 nm. Such data imply that colder temperatures (20 K) in the experimental treatment of carbonic acid ices are freezing these structures out after annealing, whereas the warmer temperature experiments (80 K) are not.
Subject(s)
Carbonic Acid , Carbonic Acid/chemistry , TemperatureABSTRACT
6-Thiopurine (6TP) is a currently prescribed drug in the treatment of diseases ranging from Crohn's disease to acute lymphocytic leukemia. While its potent mode of action is through incorporation into DNA as a thiol mimic of deoxyguanosine, severe toxicities are associated with its administration which hinder the potential therapeutic application. We have previously reported in vitro that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU, K i 7 µM), are potent inhibitors of UDP-glucose dehydrogenase (UDPGDH), an enzyme that is responsible for the formation of UDP-glucuronic acid (UDPGA), an essential substrate that is used in detoxification processes in the liver. An in vivo investigation was undertaken to probe if 6TU inhibits UDPGDH in rat hepatocytes, and it was observed that 6TU does greatly suppress the conjugation of bilirubin with UDPGA. The failed excretion of bilirubin is linked to a majority of the reported toxicities associated with 6TP administration. Efforts were undertaken for the construction of 6TP analogs, substituted at the C8 position, to reduce inhibition of UDPGDH while retaining therapeutic efficacy. Three new 6TP analogs bearing a halogen (Br, Cl, and F) at the C8 position have been achieved over five-synthetic steps in overall yields of 16 to 32%. Each of these analogs were shown to have reduced inhibition towards UDPGDH, with K i values of 192, 163, 215 µM, respectively. In addition, the bromine, chlorine, and fluorine analogs were shown to possess cytotoxicity towards the REH cell line (acute lymphocytic leukemia) having IC50 values of 9.54 µM (±0.97), 3.95 µM (±1.94), and 4.71 µM (±1.40), respectively. These three new 6TP analogs represent the first steps in the redesign of this potent anticancer agent into a better drug that possesses reduced toxic side effects while retaining therapeutic potency.
