Autopsy Case Report of Severe COVID-19 Pneumonia at a General Municipal Hospital.

We present the autopsy procedure and findings of severe coronavirus disease 2019 (COVID-19) pneumonia in an 85-year-old man. The patient required intubation immediately after admission for severe COVID-19 pneumonia. He had severe hypoxia that did not improve despite treatment with remdesivir, corticosteroids, and appropriate mechanical ventilation. On day 13, the patient developed sudden hypercapnia. His renal dysfunction subsequently worsened and became associated with hyperkalemia, and he passed away on day 15. An autopsy was performed to clarify the cause of the hypercapnic hypoxia. None of the medical personnel involved in the autopsy developed symptoms of COVID-19. Histologic examination showed various stages of diffuse alveolar damage throughout the lungs, with intra-alveolar hemorrhage in the upper zones. Microscopic examination of the kidneys revealed acute tubular necrosis. There was no significant systemic thrombosis. The autopsy findings were consistent with those typical of COVID-19.

The urinary albumin-to-creatinine ratio is a potential predictor of target lesion revascularization after percutaneous coronary intervention with coronary stents.

The association between the urinary albumin-to-creatinine ratio (UACR) and target lesion revascularization (TLR) is unknown in patients who are implanted with drug-eluting stents (DESs) or bare metal stents (BMSs) for the treatment of coronary artery disease. Of 231 Japanese patients who were implanted with DESs and/or BMSs during percutaneous coronary intervention (PCI) between July 2009 and January 2011, 118 underwent follow-up coronary angiography at 6 to 9 months after PCI; 103 were negative for qualitative tests for urine protein: 32 (31.0%)/103 patients underwent TLR for severe in-stent restenosis (ISR) and 71 did not. On the next day after admission to the hospital, first-morning-void spot urine samples were collected to calculate UACR based on urinalysis results. Pearson's product-moment correlation coefficients indicated positive associations of UACR with late loss as assessed by quantitative coronary analysis in the overall cohort, (r = +0.515, P < 0.0001), the DES subgroup (r = +0.443, P < 0.0001), and the BMS subgroup (r = +0.652, P < 0.0001). The incidence of multivessel lesions was significantly higher (P < 0.05) in the TLR group. UACR was significantly higher (P < 0.01) in the TLR group (23.88 ± 31.8 mg/gCr) than in the control group (6.29 ± 7.46 mg/gCr). Multivariate logistic regression analysis revealed UACR (odds ratio: 1.07; 95% confidence interval: 1.02-1.12; P < 0.01) to be associated with TLR. UACR was suggested to be a potential predictor of TLR required for severe ISR after PCI with coronary stents.

A case of takotsubo cardiomyopathy associated with Kounis syndrome.

A sixty-five-year old female, with a past history of variant angina and asthma, collapsed after complaining of chest pain and regained spontaneous circulation by resuscitation. An electrocardiograph showed a QS pattern on the precordial leads and sonography revealed a takotsubo cardiomyopathy-like movement. During induced hypothermic therapy for protection of her brain and heart using a drug which dilated the coronary artery, she collapsed again with ventricular flatter for 40 min; however, she re-obtained return of spontaneous circulation and eventually regained consciousness. After correction of eosinophilia by steroids, the variant angina with life-threatening arrhythmia and asthma attack subsided. She was discharged and ambulatory 14 days after admission with normal motion of the cardiac wall. This is the first case of Kounis syndrome associated with takotsubo cardiomyopathy. The mechanism of the concurrent condition of this case is herein discussed.

Primary cardiac osteosarcoma in a young man with severe congestive heart failure.

A primary cardiac malignant tumor is very rare; its prevalence is only 0.002-0.28%. Among most malignant tumors, angiosarcoma, leiomyosarcoma, and mesothelioma occupy the majority. A cardiac osteosarcoma is extremely rare: to our knowledge, only 36 cases have been reported worldwide. We present a 22-year-old case featuring severe congestive heart failure. Hemodynamically the tumor led to significant obstruction of the mitral valve. The patient underwent an emergency resection operation, but multiple metastases occurred. Though the characteristics still remain unclear because of the low prevalence, it is very important that these tumors be distinguished from benign tumors because of early resection operation.

Clinical pharmacokinetics of cytarabine formulations.

Cytarabine (cytosine arabinoside, Ara-C) is an effective chemotherapeutic agent for the treatment of acute myelogenous leukaemia and lymphocytic leukaemias. As cytarabine is an S-phase-specific drug, prolonged exposure of cells to cytotoxic concentrations is critical to achieve maximum cytotoxic activity. However, the activity of cytarabine is decreased by its rapid deamination to the biologically inactive metabolite uracil arabinoside. This rapid deamination is the reason for the ongoing search for effective formulations and derivatives of cytarabine that cannot be deaminated and exhibit better pharmacokinetic parameters. Protection of cytarabine from fast degradation and elimination has been investigated by encapsulating the drug into pharmaceutically acceptable carriers. Cytarabine derivatives have shown promise in vitro and in animal models. For example, ancitabine (cyclocytidine), enocitabine and cytarabine ocfosfate have been used clinically in Japan. Cytarabine encapsulated into multivesicular liposomes has been approved in several countries for the intrathecal treatment of lymphomatous meningitis. Although many compounds have been investigated, few cytarabine derivatives are currently available for clinical use. Further research is needed to improve the efficacy of cytarabine against haematological and solid tumours.

Bromocriptine reverses P-glycoprotein-mediated multidrug resistance in tumor cells.

One of the most important causes of anticancer treatment failure is the development of multidrug resistance (MDR). The main characteristics of tumor cells displaying the MDR phenomena are cross-resistance to structurally unrelated cytotoxic drugs having different mechanisms of action and the overexpression of the MDR1 gene, which encodes a transmembrane glycoprotein named P-glycoprotein (P-gp). This study evaluated whether bromocriptine, a D2 dopaminergic receptor agonist, influenced anticancer drug cytotoxicity and P-gp activity in a P-gp-expressing cell line compared to a non-expressing subline. The K(i) values for P-gp of cyclosporine and verapamil were 1.09 and 540 microM, respectively, and that of bromocriptine was 6.52 microM in a calcein-AM efflux assay using porcine kidney epithelial LLC-PK1 and L-MDR1 cells, overexpressing human P-gp. Bromocriptine at 10 microM reduced the IC50 of doxorubicin (DXR) in K562-DXR from 9000 to 270 ng/ml and that of vincristine (VCR) in K562-VCR from 700 to 0.30 ng/ml, whereas the IC50 values of DXR and VCR in the K562 subline were only marginally affected by these drugs. Bromocriptine restored the anticancer effect of DXR, VCR, vinblastine, vinorelbine and etoposide on MDR-tumor cells overexpressing P-gp. These observations suggest that bromocriptine has the potential to reverse tumor MDR involving the efflux protein P-gp in the clinical situation.