The late consequences of acute coronary syndrome (ACS) have been underestimated. We hypothesized that the temporal distribution of the clinically silent coronary artery disease progression (CP) is associated with the subsequent consequences of ACS.We studied 243 patients (202 men, 64 ± 10 years) with ACS undergoing percutaneous coronary intervention (PCI) during initial hospitalization. All patients underwent serial coronary angiograms (CAGs) immediately before PCI and at 7 ± 3 and 60 ± 10 months after presentation. CP was defined as an increase ≥ 15% in stenosis severity of the lesion between 2 serial CAGs. The impact of CP between each 2 serial CAGs on subsequent major adverse cardiovascular and cerebrovascular events (MACCEs) after the final CAG was examined using multivariate Cox and propensity-matched analyses.During the median follow-up duration after the final CAG of 67 months, 76 MACCEs (31.3%) were observed. Multivariate Cox proportional hazards analysis revealed that CP between the first and second CAGs (hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.32-3.94; P = 0.003) and CP between the second and final CAGs (HR, 1.96; 95% CI, 1.20-3.21; P = 0.008) were independently associated with a higher rate of MACCEs beyond the final CAG. Consistent results were obtained in the propensity score-matched analyses.CP in both the early (0-7 months) and late phases (7-60 months) were independently associated with subsequent clinical events. This may indicate the prognostic significance of persistent widespread coronary disease activity following presentation in patients with ACS undergoing PCI.
The antiherpetic effects of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in vitro and in vivo were investigated in comparison with those of acyclovir (ACV) and 5-iodo-2'-deoxyuridine (IDU). ACV was found to be consistently superior to the other two agents in antiviral activity against all ocular isolates in vitro. In vivo tests in mice, in contrast, showed DHPG in ointment form to be more effective than ACV in treating herpetic keratitis. It was noted that even 0.03% DHPG ointment was as efficacious as 0.3% ACV ointment. Other studies using the same keratitis model also demonstrated that DHPG eyedrop solution is far more effective than IDU eyedrop solution. These results indicate that DHPG can be a useful antiviral agent in the treatment of herpetic keratitis.
Background Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation (OLT). Endoscopic management by the conventional methods of biliary dilatation and/or stent placement has been successful, but sometimes severe complications occur, necessitating prolonged therapy. The aim of this study is to clarify the complications of the endoscopic approach for endoscopic dilatation and/or stent placement. Method Of 46 patients who underwent living-donor liver transplantation, 10 were diagnosed as having anatomic biliary strictures by endoscopic retrograde cholangiopancreatography (ERCP). Two patients developing biliary strictures after deceased-donor liver transplantation were also enrolled in the study. For the purpose of comparison, 302 patients with a total of 550 consecutive ERCP cases (including 115 patients with 250 malignant bile duct strictures) were recruited in this study. Success rate, number of endoscopy sessions, the median procedure time for ERCP, and incidence of complications including post-ERCP pancreatitis were compared in the OLT cases and other cases. Results The following results were obtained in the OLT cases, malignant stricture cases, and all cases, respectively: mean number of endoscopy sessions was 3.62, 2.17, and 1.94 (p = 0.0216,p < 0.0001); post-ERCP pancreatitis occurred in 5 (12.5%), 10 (4.0%), and 19 cases (3.5%) (p = 0.0327,p = 0.0093); and severe pancreatitis occurred in 2 cases of OLT. In a univariate analysis for post-ERCP pancreatitis, OLT was extracted as the only significant risk factor. Conclusions Endoscopic maneuvering for biliary dilatation and/or stent placement following OLT was associated with a higher risk of post-ERCP pancreatitis than the use of the same technique for the treatment of malignant biliary stricture. Endoscopic treatment after OLT was a significant risk factor for post-ERCP pancreatitis.
Many health care workers around the world tackled with COVID-19, however sadly, the infection of many medical care workers were reported. To reduce the risk of infection, we launched selected team (Team COVID) of non-specialists and brought in active telemedicine method and computed tomography (CT)-first protocol. We describe our actual practice and the health status of medical doctors dealing with COVID-19 patients.Between April 17, 2020 and May 24, 2020, 10 doctors worked with COVID-19 patients as part of Team COVID. The Team COVID doctors used a CT-first triage protocol for outpatients and telemedicine for inpatients and outpatients. We evaluated paired serum-specific antibodies for SARS-CoV-2 at the initial and end of the study duration and PCR results for SARS-CoV-2 at the end of the study duration. Furthermore, 36-item short-form of the Medical Outcome Study Questionnaire (SF-36) at the beginning and end of the study period were evaluated.Ten doctors worked as Team COVID: seven internal medicine doctors and three surgeons. During the study period, Team COVID treated 165 individuals in the outpatient clinic and isolated hospitalized patients for 315 person-days. There were no positive results of serum-specific antibody testing and PCR testing for SARS-CoV-2 in Team COVID doctors. Furthermore, the SF-36 showed no deterioration in physical and mental QOL status. No in-hospital infection occurred during the study period.The Team COVID fulfilled the treatment using the active telemedicine and CT-first triage protocol without in hospital infection and excess stress. The combination strategy seems acceptable for both the protection and stress relief among the medical staff.
Abstract TGF-beta is one of the most potent immunosuppressive cytokines involved in the regulation of tumor immunity. TGF-beta has three isoforms, TGF-beta1, 2 and 3. It has been demonstrated in multiple mouse tumor models that blockade of all three isoforms of TGF-beta facilitates natural tumor immunosurveillance as well as tumor vaccine efficacy. Most studies on the roles of TGF-beta in immunology are on TGF-beta1, which has been demonstrated to induce Treg cells, IL-17-producing T cells and MDSCs. Although some studies reported immunosuppressive activities of TGF-beta2, the role of TGF-beta3 in immune regulation is not well understood. In this study we asked whether it is necessary to inhibit TGF-beta3 to enhance tumor immunity induced by a tumor vaccine in a syngeneic TC1 tumor model. When the tumor reached at least 5 mm in diameter, the mice were given a peptide-based vaccine targeting HPV16 E7, which is an oncogene expressed in TC1 cells. Although the vaccine alone had minimal effects on tumor growth, combination with an anti-TGF-beta antibody that neutralizes all three isoforms significantly delayed tumor growth. A similar effect was obtained with an antibody that neutralizes only TGF-beta1 and 2 but not TGF-beta3. Thus, it is not necessary to block TGF-beta3 to overcome immune suppression. Flow cytometric analysis of immune cells in tumor draining lymph nodes and tumors showed that there was no difference in the number of Treg and MDSCs between mice with/without treatment. The vaccine significantly increased the number of tumor antigen-specific CD8+ T cells and IFN-gamma producing T cells in both lymph nodes and tumors, but there was no further increase in combination with anti-TGF-beta. The vaccine also induced a significant number of T-bet-expressing T cells (both CD4 and CD8) in both tumor draining lymph nodes and tumors, and anti-TGF-beta, regardless of TGF-beta3 blockade, further increased the number of these cells. Together the results suggested that blockade of TGF-beta1 and 2 alone is sufficient to enhance therapeutic tumor vaccine efficacy by facilitating the induction of Th1 type T cells. With the notion that TGF-beta3 might be beneficial for patients in some cancers, developing TGF-beta antagonists that do not inhibit TGF-beta3 may be lead to better outcomes. Citation Format: Masaki Terabe, Faith Robertson, Shingo Kato, Emma De Ravin, Katharine Clark, Amer M. Mizra, Jay A. Berzofsky. Blockade of TGF-beta1 and 2 without TGF-beta3 blockade is sufficient to facilitate tumor vaccine efficacy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-233. doi:10.1158/1538-7445.AM2015-LB-233
