An attenuated vaccinia vaccine encoding the SARS-CoV-2 spike protein elicits broad and durable immune responses, and protects cynomolgus macaques and human ACE2 transgenic mice from SARS-CoV-2 and its variants

As long as the coronavirus disease 2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently needed. We have developed a vaccine (rDIs-S) consisting of the attenuated vaccinia virus DIs strain platform carrying the SARS-CoV-2 S gene. rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin converting enzyme 2 (hACE2) transgenic mice, and showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA. 1 variant (TY38-839). Using a tandem mass tag (TMT) -based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that rDIs-S maintains S protein-specific antibody titers for at least 6 months after a 1st vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current and possibly future variants.

Predictors for Diarrhea After Administration of Naldemedine: Analysis Focusing on the Administration Period of Opioid Analgesics Before the Start of Naldemedine

Purpose: Naldemedine is a peripheral µ-opioid receptor antagonist, including the treatment of opioid-induced constipation (OIC) . However, diarrhea is known as its side effect. We conducted a study focusing on the administration period of opioid analgesics before the start of naldemedine to clear predictors of diarrhea due to Naldemedine. Method: All data were retrospectively collected from the electronic medical record system. We investigated patients who initially administrated naldemedine at Nagasaki University Hospital from June 1 2017 to March 31 2019. Result: One hundred thirty-two patients were subject of investigation. The incidence of diarrhea was 25.0%. The result of the multivariate analysis showed that significant predictors of diarrhea were associated with the opioid analgesics usage period longer than 7 days before naldemedine initiation (odds ratio: 3.76, 95% confidence interval: 1.53-9.20, p=0.004). Discussion: When naldemedine was used for OIC, diarrhea may be avoided by using within 7 days after opioid analgesics.

Continuous Intravenous Infusion of Oxycodone for Dyspnea from End Stage-heart Failure due to Dilated Cardiomyopathy

Introduction: Patients of end-stage heart failure often develop dyspnea. Although morphine is used for dyspnea, these patients are often inappropriate group for using morphine due to renal failure. Case: A seventy-year-old male with end-stage heart failure due to dilated cardiomyopathy developed dyspnea. We used continuous oxycodone infusion for dyspnea with small dose as an alternative to morphine due to renal failure. His dyspnea was relieved in dose-dependent without heart failure recovery. Conclusion: Oxycodone may be an alternative therapy for dyspnea with end-stage heart failure with renal failure.

A Case of Heparin-Induced Thrombocytopenia following Surgery for DeBakey Type I Acute Aortic Dissection / 日本心臓血管外科学会雑誌

A 73-year-old man underwent ascending aortic replacement and F-F crossover bypass for acute aortic dissection with right leg ischemia. He was treated postoperatively for acute renal failure due to myonephropathic metabolic syndrome (MNMS) with continuous hemodiafiltration. He suffered from acute graft occlusion and brain infarction on postoperative day (POD) 3. Although recovery of organ functions was observed, an unexpected decrease in platelet count occurred rapidly below 1.1×10⁴/μl on POD 6. We suspected heparin-induced thrombocytopenia (HIT) and all heparin administration was halted and argatroban was initiated at a dose of 0.2 μg/kg/min, with titration to achieve an activated partial thromboplastin time (APTT) of 1.5-3.0 times the initial value not to exceed 100 sec. The platelet factor 4-reactive HIT antibody was positive and definite diagnosed of HIT was made. Administration of warfarin started after the platelet count recovered to 10.0× 10⁴/μl on POD 36. Awareness of the clinical features and different presentations of HIT are essential for preventing severe complications associated with this disease.

The Result Surgical Treatment of Type A Acute Aortic Dissection. Clinical Study of Graft Replacement of Ascending Aorta With Deep Hypothermic Circulatory Arrest / 日本心臓血管外科学会雑誌

Since January, 1981 to December, 1990, eight patients (one male, 7 female) of Stanford A type aortic dissection underwent surgical treatments with deep hypothermic circulatory arrest. The average was age 59.6 years (range 50 to 72 years). All of them were diagnosed with UCG and/or CT before operation. Two cases had already been in shock state due to cardiac tamponade. Three cases had aortic insufficiency and one had neurological deficit. After median sternotomy, right atrial-femoral artery bypass was established. Right atrium was incised and coronary sinus was cannulated. Then retrograde coronary infusion of cardioplegic solution was employed at a continuous flow rate of 20ml/kg/hr. The mean rectal temperature was 19.6°C and the mean circulatory arrest time was 35.5min (22-58min). Two of eight cases died, because of DIC followed by necrotizing enteritis at 28th postoperative day, and prolonged shock state before operation. The rest were all survived without any neurological deficits. There were no severe complications related to deep hypothermia. We concluded that deep hypothermic arrest is safe and simple method, allows good inspection of operative field and makes it easier to repair the dissected aorta.