Effect of Patient's Symptom Interpretation on In-Hospital Mortality in Acute Coronary Syndrome.

BACKGROUND: The association between symptom interpretation and prognosis has not been investigated well among patients with acute coronary syndrome (ACS). As such, the present study evaluated the effect of heart disease awareness among patients with ACS on in-hospital mortality. METHODS AND RESULTS: We performed a post hoc analysis of 1,979 consecutive patients with ASC with confirmed symptom interpretation on admission between 2014 and 2018, focusing on patient characteristics, recanalization time, and clinical outcomes. Upon admission, 1,264 patients interpreted their condition as cardiac disease, whereas 715 did not interpret their condition as cardiac disease. Although no significant difference was observed in door-to-balloon time between the 2 groups, onset-to-balloon time was significantly shorter among those who interpreted their condition as cardiac disease (254 vs. 345 min; P<0.001). Moreover, the hazard ratio (HR) for in-hospital mortality was significantly higher among those who did not interpret their condition as cardiac disease based on the Cox regression model adjusted for established risk factors (HR 1.73; 95% confidence interval 1.08-2.76; P=0.022). CONCLUSIONS: This study demonstrated that prehospital symptom interpretation was significantly associated with in-hospital clinical outcomes among patients with ACS. Moreover, the observed differences in clinical prognosis were not related to door-to-balloon time, but may be related to onset-to-balloon time.

Comparing In-Hospital Outcomes for Acute Myocardial Infarction Patients in High-Volume Hospitals Performing Primary Percutaneous Coronary Intervention vs. Regional General Hospitals.

BACKGROUND: It has been reported that patients with acute myocardial infarction (AMI) transferred to low-volume primary percutaneous coronary intervention (PCI) hospitals (<115/year) in low population density areas experience higher in-hospital mortality rates. This study compared in-hospital outcomes of patients admitted to high-volume primary PCI hospitals (≥115/year) with those for other regional general hospitals.Methods and Results: Retrospective analysis was conducted on data obtained from 2,453 patients with AMI admitted to hospitals in Iwate Prefecture (2014-2018). Multivariate analysis revealed that the in-hospital mortality rate of AMI among patients in regional general hospitals was significantly higher than among patients in high-volume hospitals. However, no significant difference in mortality rate was observed among patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI. Although no significant difference was found in the in-hospital mortality rate of patients with Killip class I STEMI, significantly lower in-hospital mortality rates were observed in patients admitted in high-volume hospitals for Killip classes II, III, and IV. CONCLUSIONS: Although in-hospital outcomes for patients with STEMI undergoing primary PCI were similar, patients with heart failure or cardiogenic shock exhibited better in-hospital outcomes in high-volume primary PCI hospitals than those in regional general hospitals.

Long-term monitoring of antibody titers against microorganisms in human intravenous immunoglobulin lots derived from healthy donors in Japan manufactured during 1998-2018.

BACKGROUND: Studies evaluating long-term trends of intravenous immunoglobulin (IVIG) titers against microorganisms such as bacteria and fungi have not been conducted. We herein evaluated long-term trends of titers of IVIG lots manufactured from 1998 to 2018, derived from donors in Japan, against microorganisms affecting patients with primary or secondary immunodeficiency diseases. STUDY DESIGN AND METHODS: Titers against four strains of Pseudomonas aeruginosa, three strains of Staphylococcus aureus, four strains of Haemophilus influenzae, two strains of Klebsiella pneumoniae, one strain of Streptococcus pneumoniae, Enterococcus faecium, Bordetella pertussis, Serratia marcescens, and Candida albicans, were tested immediately after lot release in a commercial clinical testing facility in 1998. The long-term (whole period) and short-term (first and second half of the period) trends of titers were evaluated using regression analysis. RESULTS: The IVIG lots indicated meaningful titers against all microorganisms that were stable in the short term. The long-term trends could be categorized into stable, slightly decreasing, or decreasing trends, except for the metallo-ß-lactamase-producing K. pneumoniae, which indicated a slight increase. Notably, three strains of P. aeruginosa showed remarkable decreasing long-term trends in the titer. DISCUSSION: Some titers indicate decreasing trends against microorganisms over the long-term, however, is not clear whether the phenomenon diminishes the performance of IVIG. The titers of the IVIG lots could provide helpful information to optimize replacement therapy, such as considering trough values based on the titers in the patient plasma. Therefore, continuous monitoring of IVIG titers against microorganisms is important to understand titer fluctuation and epidemiological background.

Long-term monitoring of virus antibody titers in human intravenous immunoglobulin lots derived from donors in Japan.

BACKGROUND: Intravenous immunoglobulin (IVIG) contains immunoglobulin G against various viruses, except those that have been screened, such as human immunodeficiency and hepatitis C viruses. Antivirus titers reflect the serostatus of the blood donor population in the collection region and are of clinical interest. STUDY DESIGN AND METHODS: During the past 10 years, measles, mumps, rubella, varicella-zoster, hepatitis A and B, Epstein-Barr, and human respiratory syncytial viruses; human parainfluenza viruses 1, 2, and 3; human herpes simplex viruses 1 and 2; human herpesvirus 6; cytomegalovirus (CMV); human adenoviruses (HAdVs) 1, 2, 3, 7, and 11; human parvovirus B19; and human echovirus 9 and 11 titers in IVIG lots have been measured by a commercial testing facility. A viral neutralizing assay for CMV has been used at our facility. Herein, we summarize the measurements and results of a regression analysis of the trends in virus antibody titers. RESULTS: IVIG lots contained significant titers against all of the above viruses, except for HAdV 7. Three patterns-stable, increasing, and decreasing-were observed, without any drastic changes. Although these trends reflect the seroprevalence in Japan, the titers were not obviously affected by the cycle of epidemics. On the other hand, the prevalence data suggest that titers against hepatitis A virus and other viruses will decrease in the near future, although they are currently stable. CONCLUSION: Monitoring the titer of IVIG lots and seroprevalence of donor populations is important for anticipating future changes in virus antibody titers of IVIG lots and can provide useful information of clinical interest.

Neutralizing activities against seasonal influenza viruses in human intravenous immunoglobulin.

Influenza viruses A/H1N1, A/H3N2, and B are known seasonal viruses that undergo annual mutation. Intravenous immunoglobulin (IVIG) contains anti-seasonal influenza virus globulins. Although the virus-neutralizing (VN) titer is an indicator of protective antibodies, changes in this titer over extended time periods have yet to be examined. In this study, variations in hemagglutination inhibition (HI) and VN titers against seasonal influenza viruses in IVIG lots over extended time periods were examined. In addition, the importance of monitoring the reactivity of IVIG against seasonal influenza viruses with varying antigenicity was evaluated. A/H1N1, A/H3N2, and B influenza virus strains and IVIG lots manufactured from 1999 to 2014 were examined. The HI titer was measured by standard methods. The VN titer was measured using a micro-focus method. IVIG exhibited significant HI and VN titers against all investigated strains. Our results suggest that the donor population maintains both specific and cross-reactive antibodies against seasonal influenza viruses, except in cases of pandemic viruses, despite major antigen changes. The titers against seasonal influenza vaccine strains, including past strains, were stable over short time periods but increased slowly over time.

Optical manipulation of the alpha subunits of heterotrimeric G proteins using photoswitchable dimerization systems.

Alpha subunits of heterotrimeric G proteins (Gα) are involved in a variety of cellular functions. Here we report an optogenetic strategy to spatially and temporally manipulate Gα in living cells. More specifically, we applied the blue light-induced dimerization system, known as the Magnet system, and an alternative red light-induced dimerization system consisting of Arabidopsis thaliana phytochrome B (PhyB) and phytochrome-interacting factor 6 (PIF6) to optically control the activation of two different classes of Gα (Gαq and Gαs). By utilizing this strategy, we demonstrate successful regulation of Ca2+ and cAMP using light in mammalian cells. The present strategy is generally applicable to different kinds of Gα and could contribute to expanding possibilities of spatiotemporal regulation of Gα in mammalian cells.

Superior mesenteric artery syndrome treated with single-incision laparoscopy-assisted duodenojejunostomy.

Superior mesenteric artery (SMA) syndrome is an uncommon disease resulting from compression and partial obstruction of the third portion of the duodenum from the SMA. A 77-year-old man, who did not have a history of surgery, experienced repeated vomiting and developed abdominal distension. Abdominal CT showed a narrowed third portion of the duodenum, with a distended stomach and proximal duodenum. The patient was diagnosed as having SMA syndrome and was initially treated conservatively, but his condition did not improve. Single-incision laparoscopy-assisted duodenojejunostomy was performed. The patient recovered well and was discharged from hospital on postoperative day 8. Laparoscopic treatment is feasible for the treatment of SMA syndrome given its safety and minimal invasiveness. This is a report of the first case of single-incision laparoscopy-assisted duodenojejunostomy. This procedure is safer and less invasive than a conventional laparoscopic approach in a patient with SMA syndrome.

Adjuvant chemotherapy with S-1 followed by docetaxel for gastric cancer and CY1P0 peritoneal metastasis after relatively curative surgery.

OBJECTIVE: The aim of this study was to assess the feasibility and safety of adjuvant chemotherapy with S-1 followed by docetaxel. PATIENTS AND METHOD: Twenty-eight patients with advanced gastric cancer underwent gastrectomy without preoperative chemotherapy. These patients were divided into 3 groups on the basis of cytologic results of peritoneal lavage (CY) and the presence of local peritoneal metastatic nodules (P): CY1-P0, CY0-P1, and CY1-P1. Oral S-1 (80 mg/m(2)/day) was administered for 3 consecutive weeks, followed by intravenous docetaxel (35 mg/m(2)) on days 29 and 43 (1 cycle). This cycle was repeated every 8 weeks. The primary endpoint was the ability to complete 6 cycles of S-1 followed by docetaxel. The secondary endpoints were safety, progression-free survival, mean survival time (MST), and overall survival (OS). RESULTS: The subjects were 18 men and 10 women (39 to 78 years old, median age, 64 years). The extent of peritoneal metastasis was CY1-P0 in 8 patients, CY0-P1 in 14 patients, and CY1-P1 in 6 patients. Both hematologic and nonhematologic toxicities were generally mild. The completion rate of the planned 6 cycles of the protocol was 71.4% (20 of 28 patients). Median progression-free survival was 22.9 months, and the 2-year survival rate was 78.6%. The overall MST was 34.3 months, and the MST by group was 34.5 for CY1-P0, 34.3 for CY0-P1, and 19.3 months for CY1-P1. The OS in the CY1-P0 and CY0-P1 groups was significantly longer than that in the CY1-P1 group (P<0.05). CONCLUSION: Adjuvant chemotherapy with S-1 followed by docetaxel is safe and well tolerated and has the potential to improve OS in patients with a status of CY1P0 following relatively curative resection.

Spermatic cord tumor metastatic from stomach cancer 1 year after curative gastrectomy.

We report a case of advanced stomach cancer metastatic to the spermatic cord 1 year after curative distal gastrectomy. The patient underwent distal gastrectomy with D2 lymph node dissection. There was no metastasis to the liver or peritoneum, and cytologic examination of the peritoneal lavage fluid was negative for cancer cells (CY0). Histological examination revealed a moderately differentiated tubular adenocarcinoma that had penetrated the serosa (T4a). Postoperative staging was T4aN1M0, stage IIIA, according to the Japanese gastric carcinoma classification scale. One year after the operation, the patient was readmitted with right groin pain. Percutaneous fine needle aspiration biopsy of the inguinal tumor revealed a tubular adenocarcinoma. Extirpation of the inguinal tumor with wedge resection of the right iliac-femoral vein was performed. Pathological examination revealed a moderately differentiated tubular adenocarcinoma that had diffusely infiltrated the connective tissue surrounding the spermatic cord. Immunohistochemical studies showed the tumor cells were reactive for CK7 but not for CK20. These findings were consistent with the diagnosis of a spermatic cord tumor metastatic from a known gastric primary cancer. Laparoscopic exploration showed invagination of the peritoneum with small nodules from the median umbilical fold to the lateral umbilical fold and a markedly decreased distance between the folds. Pathological examination in this area revealed a tubular structure consisting of mesothelial cells within the cancer tissue which was associated with dense fibrosis, suggesting that the invagination of the peritoneum had been caused by minimal peritoneal metastasis.

Supportive techniques and devices for endoscopic submucosal dissection of gastric cancer.

The indications for endoscopic treatment have expanded in recent years, and relatively intestinal-type mucosal stomach carcinomas with a low potential for metastasis are now often resected en bloc by endoscopic submucosal dissection (ESD), even if they measure over 20 mm in size. However, ESD requires complex maneuvers, which entails a long operation time, and is often accompanied by complications such as bleeding and perforation. Many technical developments have been implemented to overcome these complications. The scope, cutting device, hemostasis device, and other supportive devices have been improved. However, even with these innovations, ESD remains a potentially complex procedure. One of the major difficulties is poor visualization of the submucosal layer resulting from the poor countertraction afforded during submucosal dissection. Recently, countertraction devices have been developed. In this paper, we introduce countertraction techniques and devices mainly for gastric cancer.

Localization of cytochrome P4502E1 enzyme in normal and cancerous gastric mucosa and association with its genetic polymorphism in unoperated and remnant stomach.

BACKGROUND: Exposure to nitroso compounds and the activity of cytochrome P450 2E1 (CYP2E1), an activation enzyme for these carcinogens, are important factors in gastric carcinogenesis. Here, we investigated the potential correlation between genetic variation in CYP2E1 and its enzyme expression as detected with immunohistochemical (IHC) staining and cancer susceptibility in unoperated and remnant stomach. METHODS: Expression of CYP2E1 in the stomach (n=117) was detected with IHC staining using a polyclonal anti-CYP2E1 antibody. Interindividual variation in CYP2E1 enzyme activity was then compared with genetic polymorphisms in the transcriptional flanking region of the CYP2E1 gene by restriction fragment length polymorphism (RFLP) detection using the Rsa I restriction enzyme. Genetic polymorphisms of Rsa I RFLP in CYP2E1 were investigated in 499 patients with gastric cancer (466 unoperated stomachs and 33 remnant stomachs) and 553 control patients with benign gastroduodenal diseases. RESULTS: Mucosal IHC staining for CYP2E1 was stronger in areas of intestinal metaplasia, particularly in endocrine cells, which stained consistently and strongly. Expression of CYP2E1 enzyme in areas of IHC staining were confirmed with Western blot analysis and showed a significant association between the degree of staining and the CYP2E1 genotype (p<0.01) in cancer tissues and in the foveolar epithelium of normal gastric mucosa. No association between specific CYP2E1 genotype and gastric cancer risk in the unoperated stomach was found in either the large study or the age- and gender-matched case-control study. However, the frequency of rare alleles (C1/C2 or C2/C2) was significantly higher in patients with cancer in the remnant stomach following gastrectomy than in controls subjects without cancer (odds ratio=2.8, 95% confidence interval=1.3-5.8) or those with primary gastric cancer (odds ratio=2.6, 95% confidence interval=1.3-5.5). CONCLUSIONS: CYP2E1 genetic polymorphisms might correlate with CYP2E1 enzyme expression levels in normal and cancerous gastric tissues. These polymorphisms do not influence the development of primary stomach cancer but may do so in specific conditions, such as the remnant stomach after gastrectomy.

Enalapril suppresses ventricular remodeling more effectively than losartan in patients with acute myocardial infarction.

BACKGROUND: Ventricular remodeling after acute myocardial infarction (AMI) is associated with increased morbidity and mortality. ELITE II study showed that losartan, an angiotensin receptor blocker, shows a survival benefit to the same degree as captopril, an angiotensin-converting enzyme inhibitor, does in patients with heart failure. However, recent OPTIMAAL study showed that clinical outcomes after losartan are not superior to those after captopril in patients with AMI. We examined the effect of losartan on ventricular remodeling after AMI comparatively with that of enalapril. METHODS: We enrolled 203 consecutive patients with AMI (mean age 62 +/- 11 years). All patients underwent primary percutaneous coronary intervention and were randomly assigned to losartan (25-50 mg, n = 101) or enalapril (2.5-10 mg, n = 102) treatment. Biplane left ventriculography was performed just after primary percutaneous transluminal coronary angioplasty (acute phase) and 6 months after the onset of AMI. RESULTS: Any of the maximal creatine kinase level, left ventricular end-diastolic volume index, end-systolic volume index, and ejection fraction measured at acute phase was not different between losartan and enalapril groups. However, changes in left ventricular end-diastolic index (18 +/- 25 vs 8 +/- 24 mL/m2) and left ventricular end-systolic volume index (10 +/- 20 vs 2 +/- 18 mL/m2) from acute phase to 6 months were significantly greater in losartan than in enalapril group. Change in left ventricular ejection fraction (0.2% +/- 10.3% vs 3.4% +/- 11.6%) from acute phase to 6 months was significantly smaller in losartan than in enalapril group. The plasma level of brain natriuretic peptide at 6 months was significantly higher in losartan than in enalapril group (all P < .05). CONCLUSION: These indicate that enalapril suppresses ventricular remodeling after AMI more effectively than losartan.

Circulating level of gelatinase activity predicts ventricular remodeling in patients with acute myocardial infarction.

BACKGROUND: Matrix metalloproteinase (MMP) plays an important role in the development of ventricular remodeling in an animal model of acute myocardial infarction (AMI). We examined whether circulating MMP activity can predict left ventricular (LV) remodeling after AMI in humans. METHODS: We measured the circulating level of MMP-2 and MMP-9 activities (gelatinase activity) at 14 days after the onset of AMI by gelatin zymography in 52 consecutive patients (age 62+/-2). All patients underwent direct PTCA and stenting at an acute stage, and were treated subsequently with losartan or enalapril. Biplane left ventriculography was performed at admission, and 2 weeks and 6 months after the onset of AMI. RESULTS: We expressed gelatinolysis activity as the ratio to MMP-2 standard. Mean gelatinase activity was 0.721+/-0.013. We divided patients into two groups, groups with gelatinolysis activity <0.72 (low group, n=27) and >0.72 (high group, n=25). Either change in LV end-diastolic volume index (LVEDVI, ml/m(2)) or end-systolic volume index (LVESVI, ml/m(2)) from admission to 2 weeks was not different between the two groups. Changes in both LVEDVI and LVESVI from 2 weeks to 6 months were greater in high gelatinolysis activity group than those in low activity group. Moreover, circulating level of gelatinolysis activity was positively correlated with changes in LVEDVI and LVESVI from 2 weeks to 6 months. CONCLUSION: These results demonstrate that circulating level of gelatinase activity can predict LV remodeling after AMI. Inhibition of gelatinase activity at the acute phase may be a therapeutic strategy for the prevention of remodeling after AMI.

Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation.

BACKGROUND: Early reperfusion therapy improves the clinical outcomes of patients with acute myocardial infarction (AMI), but benefits are limited by reperfusion injury in some patients. We examined the effect of nicorandil, a hybrid of K(ATP) channel opener and nicotinamide nitrate, on reactive oxygen species (ROS) formation and clinical outcomes after primary percutaneous coronary intervention (PCI) for AMI. METHODS: Fifty-eight patients with AMI were randomized into control (n = 25) and nicorandil pretreatment groups (n = 33). In the nicorandil group, nicorandil (4 mg as a bolus injection followed by constant infusion at 8 mg/hour for 24 hours) was administered just after admission. ROS formation was assessed by measuring urinary excretion of 8-epi-prostaglandin F2alpha (PGF2alpha) and compared between the 2 groups. Cardiac function and the incidence of reperfusion injury and cardiac events were also compared. RESULTS: Urinary 8-epi-PGF2alpha excretion was increased 2-fold at 60 to 90 minutes after PCI in the control group, whereas it was unchanged after PCI in the nicorandil group (P <.0001 between the 2 groups). The incidence of no-reflow phenomenon was lower in the nicorandil group than in the control group. Left ventricular ejection fraction and cardiac index at 6 months were greater in the nicorandil group than in controls. Plasma brain natriuretic peptide level at 6 months was lower in the nicorandil group. Incidences of inhospital cardiac events and rehospitalization were lower in the nicorandil group than in controls. CONCLUSIONS: Nicorandil improves cardiac function and clinical outcomes in patients with AMI. Suppression of ROS formation may be involved in the mechanism.

Surgical outcome of 483 patients with early gastric cancer: prognosis, postoperative morbidity and mortality, and gastric remnant cancer.

BACKGROUND/AIMS: The aim of this retrospective study was to evaluate the characteristics, treatment, postoperative morbidity, mortality, and prognosis of early gastric cancer patients as well as the incidence of gastric remnant cancer after curative surgery based on an analysis of the surgical results of Nippon Medical School Hospital over the past 10 years (1991-2000). METHODOLOGY: Out of 1057 patients with gastric cancer (all stages), 483 patients (301 males and 182 females; mean age 60.9 years) underwent surgery for early gastric cancer. Early gastric cancer, defined as that invading the m or sm layer regardless of lymph node metastasis, was classified according to the Japanese Classification of Gastric Carcinoma. The survival rate was calculated using the Kaplan-Meier method. RESULTS: The stages of the 483 patients were as follows: stage Ia patients, 443 cases; stage Ib, 29 cases; stage II, 7 cases; and stage IV, 4 cases. The overall 5- and 10-year survival rates were 95.9% and 95.9% for stage Ia, 82.9% and 80.2% for stage Ib, 73.2% and 68.6% for stage II and 0% for stage IV, respectively. No difference was observed in the 5- and 10-year survival rates between patients with D1 and D2 dissections in cases without lymph node metastasis. In patients with n1 positive sm cancer, however, the 5-year survival rate of the patients who underwent D2 dissection was 91.0% while that of those who underwent D1 dissection was 80.0% (P<0.05). The incidences of postoperative morbidity from various cancers included 4.2% from surgical site infections, 1.6% from anastomotic dehiscence, 1.6% from intestinal obstructions, and 3.9% from respiratory and/or heart dysfunction. Three patients (0.6%) died of multiple organ failure. Five patients who had undergone gastrectomy for early gastric cancer were diagnosed as having early cancer in the gastric remnant during a periodic follow-up endoscopy and underwent regastrectomy. CONCLUSIONS: The prognosis of early gastric cancer is usually excellent, and the morbidity and mortality rates are satisfactory. D2 lymph node dissection is necessary in patients with n1 positive sm cancer. Periodic follow-up endoscopies in gastrectomized patients may be useful for the early detection of gastric remnant cancer.

Synthesis and structural characterization of the first unsymmetrical diarylpalladium complex trans-Pd(C6F5)(2,4,6-C6F3H2)(PEt3)2, derived from transmetallation between 2,4,6-trifluorophenylboronic acid and trans-Pd(C6F5)I(PEt3)2.

The reactions of 2,4,6-trifluorophenylboronic acid with aryl(iodo)palladium(ii) complexes, trans-Pd(C(6)F(5))I(PR(3))(2)(PR(3)= PEt(3), PMe(2)Ph, PMePh(2)) in the presence of Ag(2)O afforded trans-Pd(C(6)F(5))(2,4,6-C(6)F(3)H(2))(PR(3))(2) which are stabilized by fluorine atoms in the ortho positions.

Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction.

Allopurinol, an inhibitor of xanthine oxidase, was shown to improve the regional ventricular function after coronary artery occlusion and reperfusion in animal models. The effects of oral administration of allopurinol on a transient increase in free radical generation after primary percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI) and on their clinical outcomes were examined. Thirty-eight AMI patients undergoing primary PTCA were randomly assigned to control (group 1, n = 20) and allopurinol treatment groups (group 2, n = 18). Allopurinol (400 mg) was administered orally just after the admission (approximately 60 min before reperfusion). Free radical production was assessed by successive measurement of urinary excretion of 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) after PTCA. Urinary 8-epi-PGF(2alpha) excretion was increased by twofold at 60-90 min after PTCA compared with the baseline value in group 1. This increase was completely inhibited in group 2. Plasma allopurinol concentration was 1,146 +/- 55 ng/ml in group 2 when reperfusion was achieved. Slow flow in the recanalized coronary artery after PTCA occurred less frequently in group 2 than in group 1. Cardiac index determined just after reperfusion and left ventricular ejection fraction at 6 months after PTCA were both significantly greater in group 2 than in group 1 although pulmonary capillary wedge pressure was similar in the two groups. In conclusion, allopurinol pretreatment is effective in inhibiting generation of oxygen-derived radicals during reperfusion therapy and the recovery of left ventricular function in humans.