Mechanistic Study of the Oxidative Degradation of the Triazole Antifungal Agent CS-758 in an Amorphous Form

In this study, the degradates generated from a pharmaceutical solid were characterized, and a mechanistic pathway underlying their formation was proposed. The chemical stability of a novel triazole antifungal drug, CS‐758, deteriorated significantly when the crystal was disordered, and characteristic degradates were generated. A total of eight degradates in solution and nine degradates in a solid state were isolated by preparative liquid chromatography. Degradates were characterized using high‐performance liquid chromatography–photodiode array, mass spectrometry, and nuclear magnetic resonance. Radical‐mediated oxidation is proposed as the main degradation pathway in the solid state. The initiation step of this pathway is hydrogen atom abstraction from a methine carbon that is adjacent to a dien moiety and the formation of a delocalized vinylic radical intermediate. Molecular oxygen is then added to the radical position to form hydroperoxides. There are three potential oxidation routes based on the proposed autoxidation pathway that lead to the generation of the dioxane ring‐opening hydroxyl form, the 9,10‐epoxide form, or the 11,12‐epoxide form, depending on the substituted position of the added molecular oxygen. The epimer compound generated via the vinylic radical intermediate and sulfoxides was characterized. This degradation mechanism provides the scientific foundation for an oxidative stressing system currently under investigation.     

Japanese orthopaedic association cervical myelopathy evaluation questionnaire (JOACMEQ): Part 5. Determination of responsiveness

Background

In 1999, the Japanese Orthopaedic Association decided to develop a new Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The final version of the JOACMEQ, comprising 24 questions and five domains (cervical spine function (CF); upper extremity function (UF); lower extremity function (LF); bladder function (BF); and quality of life (QOL)), was established after three nationwide investigations. The fourth investigation, reported in this paper, was performed to confirm the responsiveness of the questionnaire.

Monte Carlo simulation of sensitivity and NECR of an entire-body PET scanner

The current positron emission tomography (PET) design is aimed toward establishing an entire-body PET scanner. An entire-body PET scanner is a scanner whose axial field of view (FOV) covers the whole body of a patient, whereas whole-body PET scanner can be of any axial FOV length, but was designed for a whole-body scan. Despite its high production cost, an entire-body depth-of-interaction PET scanner offers many benefits, such as shorter and dynamic PET time acquisition, as well as higher sensitivity and count rate performance. This PET scanner may be cost-effective for clinical PET scanners with high scan throughput. In this work, we evaluated the sensitivity and count rate performance of a 2-m-long PET scanner with conventional data acquisition (DAQ) architecture, using Monte Carlo simulation, and we evaluated two ring diameters (60 and 80 cm) to reduce the scanner cost. From simulation of scanning with a 2-m axial FOV, the sensitivity for a 2-m-long PET scanner of 60 and 80-cm diameter is around 80 and 68 times higher, respectively, than that of the conventional PET scanner. In addition, for the 2-m-long PET scanner with 60-cm diameter, the peak noise equivalent count rate (NECR) was 843 kcps at 125 MBq, whereas the peak for the 80-cm diameter was 989 kcps at 200 MBq. This shows gains of 15.3 and 17.95, respectively, in comparison with that of the conventional PET scanner. The 2-m-long PET scanner with 60-cm ring diameter could not only reduce the number of detectors by 21 %, but also had a 17 % higher sensitivity compared to that with an 80-cm ring diameter. On the other hand, despite the higher sensitivity, the NECR of the 60-cm ring diameter was smaller than that of the 80-cm ring diameter. This results from the single data loss due to dead time, whereas grouping of axially stacked detectors was used in the conventional DAQ architecture. Parallelization of the DAQ architecture is therefore important for the 2-m-long PET scanner to achieve its optimal performance.     

Association Between Anti-Helicobacter pylori Antibody Seropositive and De Novo Gallstone Formation After Laparoscopic Sleeve Gastrectomy for Japanese Patients with Severe Obesity

Purpose

Patients who have undergone bariatric surgery are at risk for gallstone formation. However, the incidence of gallstone formation after bariatric surgery has not been adequately studied in the Japanese population. We aimed to elucidate the incidence and risk factors for gallstone formation after laparoscopic sleeve gastrectomy (LSG) for Japanese patients with severe obesity.

Methods

We conducted a retrospective cohort study among patients with severe obesity treated with LSG between April 2017 and June 2020 at two institutions. Patients who had received previous cholecystectomy, had preoperative gallstones, and had received postoperative prophylactic ursodeoxycholic acid were excluded. Body weight, body mass index, and blood data were collected at each follow-up visit before and after the surgery. Follow-up abdominal ultrasonography was performed 6–12 months after surgery, and the incidence of gallstones was calculated. The association between the data and gallstone formation was evaluated.

Results

During the study period, we performed LSG for 98 patients. Of these, 61 cases remained by above conditions and were examined using abdominal ultrasonography over 6 months after surgery. The incidence of gallstones was 23.0% and that of symptomatic gallstones was 3.3%. Anti-Helicobacter pylori antibody seropositive and titer were the only factors that showed significant association with de novo gallstone formation after LSG.

Conclusions

Anti-Helicobacter pylori antibody seropositive may be associated with de novo gallstone formation after LSG for Japanese patients with severe obesity.

Graphical abstract