[Three cases of COVID-19 in elderly patients with delayed release from isolation due to persistent positive polymerase chain reaction findings].

The coronavirus disease 2019 (COVID-19) infection has spread worldwide, with no sign of its control in Japan yet. Eight elderly COVID-19 patients over 90 years of age were treated at our hospital. We herein report three cases with characteristic progression. Case 1 was a 91-year-old female patient diagnosed with bacterial pneumonia previously who did not show improvement with medication; thus, she was transferred to our hospital 16 days after the onset. She was diagnosed with COVID-19 using the SARS-CoV-2 polymerase chain reaction (PCR) test. Favipiravir, methylprednisolone, and unfractionated heparin were administered, but she only tested negative 68 days after the onset, at which point she was discharged. However, she was transferred back to our hospital 80 days after the onset since she tested positive again. She was transferred to another hospital 110 days after the onset without testing negative. Case 2 was a 102-year-old female. Despite being a mild case, it took 32 days to obtain negative PCR findings, leading to a decline in the activities of daily living. Case 3 was a 90-year-old male patient treated with favipiravir, dexamethasone, and unfractionated heparin, but his condition deteriorated. He never tested negative for PCR and ultimately died 20 days after the onset. Reports suggest that PCR positivity does not necessarily indicate infectivity, but there are no clear criteria for lifting a quarantine. Therefore, PCR negativity is often sought for "peace of mind." In the current situation where hospitals are fully occupied, clear criteria for lifting the quarantine should be promptly determined. After the completion of treatment, it is more important to monitor symptoms and take standard precautions, such as daily health monitoring, wearing a mask, and keeping an appropriate distance from others, than to obtain a negative PCR result.

Plasminogen activator inhibitor-1 deficiency has renal benefits but some adverse systemic consequences in diabetic mice.

BACKGROUND: Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) are observed in patients with obesity, hypertension and diabetes, and several observations suggest that PAI-1 mediates diabetic vascular complications. Although increased intrarenal expression of PAI-1 is also a feature of diabetic nephropathy, evidence that PAI-1 plays a primary pathogenetic role in the renal pathology is lacking. METHODS: This study was designed to investigate the renal effects of genetic PAI-1 deficiency in db/db mice with obesity, hyperinsulinemia and hyperglycemia. For comparison the effects of PAI-1 deficiency were also examined in a cohort of mice with insulin-deficient streptozotocin (STZ)-induced diabetes. The findings are reported for 4 study groups at 8 months of age: PAI-1+/+ controls, PAI-1+/+ diabetics, PAI-1-/- controls and PAI-1-/- diabetics. RESULTS: PAI-1 deficiency had an unexpected negative impact on the db/db mice. Overall 33% of the diabetic mice died prematurely, and 63% of the db/db PAI-1-/- males had an obese body habitus but were runts. The final analyses were limited to the female db/db mice. Several nephropathy parameters were improved in the db/db PAI-1-/- group compared to the db/db PAI-1+/+ group including: albumin-to-creatinine ratios (57 +/- 45 vs. 145 +/- 71 microg/mg x10), change in glomerular extracellular matrix (ECM) area (decrease of 10% compared to controls vs. an increase of 31%) and increased total kidney collagen (47% increased vs. 96% in the PAI-1+/+ diabetics). The serum glucose levels were 15-25% lower in the PAI-1-/- nondiabetic control groups and remained lower in the db/dbPAI-1-/- mice. The STZ study was performed in males. None of the mice developed a runted phenotype or died prematurely. After diabetes of 6 months' duration changes in glomerular ECM area (-15 vs. +64%) and total kidney collagen (+8 vs. +40%) were lower in the PAI-1-/- mice compared to the PAI-1+/+ mice. The serum cholesterol levels were significantly lower in the PAI-1-/- mice, both controls (47 +/- 3 vs. 53 +/- 10 mg/dl) and diabetics (48 +/- 3 vs. 74 +/- 9 mg/dl). CONCLUSION: These data suggest a direct role for PAI-1 in renal matrix expansion and metabolic control in diabetes, but they also highlight important adverse outcomes that include male runting and premature death in mice with diabetes due to an inactive leptin receptor.

Impaired taste acuity in patients with diabetes mellitus on maintenance hemodialysis.

AIMS: It has been reported that taste acuity for the four primary tastes, sour, sweet, salty and bitter, is impaired in hemodialysis (HD) patients. However, there have been no studies reported on taste acuity of diabetic HD patients. The present study aimed to quantify and compare the taste acuity of diabetic and non-diabetic HD patients, and further to determine if there were correlations between diminished taste acuity and certain blood serum parameters typically askew in hemodialysis patients. METHODS: In a test group of 24 diabetic and 24 non-diabetic HD patients matched for age, body mass index and duration of HD, taste acuity for the four tastes was determined by asking patients to identify them at varying concentrations. RESULTS: Statistical analyses indicate that bitter and total taste acuity were significantly impaired in diabetic HD patients. In diabetic HD patients, correlation was found between sweet, salty or total taste acuity and blood urea nitrogen or normalized protein catabolic rate. CONCLUSIONS: We conclude that taste acuity is partially impaired in diabetic HD patients, and suggest this contributes to reduced appetite, leading to malnutrition and poor prognoses.

Multifunctionality of PAI-1 in fibrogenesis: evidence from obstructive nephropathy in PAI-1-overexpressing mice.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) has been implicated in the pathogenesis of chronic kidney disease based on its up-regulated expression and on the beneficial effects of PAI-1 inhibition or depletion in experimental models. PAI-1 is a multifunctional protein and the mechanisms that account for its profibrotic effects have not been fully elucidated. METHODS: The present study was designed to investigate PAI-1-dependent fibrogenic pathways by comparing the unilateral ureteral obstruction model (UUO) (days 3, 7, and 14) in PAI-1-overexpressing mice (PAI-1 tg) to wild-type mice, both on a C57BL6 background. RESULTS: Following UUO, total kidney PAI-1 mRNA and/or protein levels were significantly higher in the PAI-1 tg mice (N= 6 to 8/group) and fibrosis severity was significantly worse (days 3, 7, and 14), measured both as Sirius red-positive interstitial area (e.g., 10 +/- 3.2% vs. 4.5 +/- 1.0%) (day 14) and total kidney collagen (e.g., 11.1 +/- 1.7 vs. 6.2 +/- 1.3 microg/mg) (day 14). By day 14, the expression of two normal tubular proteins, E-cadherin and Ksp-cadherin, were significantly lower in the PAI-1 tg mice (3.2 +/- 0.5% vs. 11.7 +/- 5.9% and 2.6 +/- 1.6) vs. 6.2 +/- 0.8%, respectively), implying more extensive tubular damage. At least four fibrogenic pathways were differentially expressed in the PAI-1 tg mice. First, interstitial macrophage recruitment was more intense (P < 0.05 days 3 and 14). Second, interstitial myofibroblast density was greater (P < 0.05 days 3 and 7) despite similar numbers of proliferating tubulointerstitial cells. Third, transforming growth factor-beta1 (TGF-beta1) and collagen I mRNA were significantly higher. Finally, urokinase activity was significantly lower (P < 0.05 days 7 and 14) despite similar mRNA levels. Gene microarray studies documented that that the deletion of this single profibrotic gene had far-reaching consequences on renal cellular responses to chronic injury. CONCLUSION: These data provide further evidence that PAI-1 is directly involved in interstitial fibrosis and tubular damage via two primary overlapping mechanisms: early effects on interstitial cell recruitment and late effects associated with decreased urokinase activity.