Semiquantitative Analysis by Scanning Electron Microscopy of Cochlear Hair Cell Damage by Ototoxic Drugs

The ototoxicity of cisplatin and carboplatin in the organ of Corti of the guinea pig was evaluated semiquantitatively. Damage of the stereocilia of outer hair cells (OHCs) observed by scanning electron microscopy (SEM) was classified into normal, grade 1 (10-50% loss of stereocilia), grade 2 (less than 50% remaining stereocilia), or grade 3 (missing stereocilia). The OHCs observed by light microscopy (LM) were classified as remaining or missing cells. Fifty OHCs of each row in the middle part of each turn of the cochlea were counted (a total of 150 cells per turn). Guinea pigs were administered 5 mg/kg of cisplatin or 50 mg/kg of carboplatin intraperitoneally for three consecutive days. In groups 1 and 2, in which both cochleae were fixed in 2.5% glutaraldehyde and 1% osmium tetroxide (OsO4) and observed by SEM, the percentages of damage of the OHC stereocilia were similar in each cochlear turn bilaterally. In group 3, the right cochleae were fixed in OsO4 and observed by phase contrast microscopy as surface preparations. Left cochleae were submitted for SEM observation. Missing and grade 3 cells were observed at similar percentages in each row of each turn. In group 4, succinate dehydrogenase staining was performed in the right cochleae and observed by LM. The degree of damage in the right cochleae was compared with that of the left cochleae which was observed by SEM. On average, the mean numbers of missing cells and cells showing grade 3 damage were similar in each row of each turn. From these similarities of evaluation of ototoxicity at LM and SEM levels, it was concluded that semiquantitative analysis by SEM only is appropriate for the assessment of ototoxicity

Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.

AIM: There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. RESULTS: Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. CONCLUSIONS: In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission

The current status of thrombosis and anticoagulation therapy in patients with COVID-19 in Japan: From the CLOT-COVID study

BACKGROUND: Data on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. RESULTS: Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. CONCLUSIONS: In the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19

Effects of Renal Function on Urinary Excretion and Serum Concentration of Uric Acid in Patients Treated with Febuxostat for Chronic Kidney Disease

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Use of the Japanese Version of the Montreal Cognitive Assessment to Estimate Cognitive Decline in Patients Aged 75 Years or Older with and without Type 2 Diabetes Mellitus

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