Influence of psychiatric or social backgrounds on clinical decision making: a randomized, controlled multi-centre study.

BACKGROUND: Frequent and repeated visits from patients with mental illness or free medical care recipients may elicit physicians' negative emotions and influence their clinical decision making. This study investigated the impact of the psychiatric or social background of such patients on physicians' decision making about whether to offer recommendations for further examinations and whether they expressed an appropriate disposition toward the patient. METHODS: A randomized, controlled multi-centre study of residents in transitional, internal medicine, or emergency medicine was conducted in five hospitals. Upon randomization, participants were stratified by gender and postgraduate year, and they were allocated to scenario set 1 or 2. They answered questions pertaining to decision-making based on eight clinical vignettes. Half of the eight vignettes presented to scenario set 1 included additional patient information, such as that the patient had a past medical history of schizophrenia or that the patient was a recipient of free care who made frequent visits to the doctor (biased vignettes). The other half included no additional information (neutral vignettes). For scenario set 2, the four biased vignettes presented to scenario set 1 were neutralized, and the four neutral vignettes were rendered biased by providing additional information. After reading, participants answered decision-making questions regarding diagnostic examination, interventions, or patient disposition. The primary analysis was a repeated-measures ANOVA on the mean management accuracy score, with patient background information as a within-subject factor (no bias, free care recipients, or history of schizophrenia). RESULTS: A total of 207 questionnaires were collected. Repeated-measures ANOVA showed that additional background information had influence on mean accuracy score (F(7, 206) = 13.84, p <  0.001 partial η2 = 0.063). Post hoc pairwise multiple comparison test, Sidak test, showed a significant difference between schizophrenia and no bias condition (p <  0.05). The ratings for patient likability were lower in the biased vignettes compared to the neutral vignettes, which was associated with the lower utilization of medical resources by the physicians. CONCLUSIONS: Additional background information on past medical history of schizophrenia increased physicians' mistakes in decision making. Patients' psychiatric backgrounds should not bias physicians' decision-making. Based on these findings, physicians are recommended to avoid being influenced by medically unrelated information.

Near-infrared spectroscopy monitoring during out-of-hospital cardiac arrest: can the initial cerebral tissue oxygenation index predict ROSC?

STUDY OBJECTIVES: Near-infrared spectroscopy is a modality that can monitor tissue oxygenation index (TOI) and has potential to evaluate return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). This study's objectives were to evaluate whether TOI could be associated with ROSC and used to help guide the decision to either terminate CPR or proceed to extracorporeal CPR (ECPR). METHODS: In this observational study, we assessed the patients with out-of-hospital cardiac arrest with non-traumatic cause receiving CPR on arrival at our ED between 2013 and 2016. TOI monitoring was discontinued either on CPR termination after ROSC was reached or on patient death. Patients were classified into two groups: ROSC and non-ROSC group. RESULTS: Out of 141 patients, 24 were excluded and the remaining 117 were classified as follows: ROSC group (n=44) and non-ROSC group (n=73). ROSC group was significantly younger and more likely to have their event witnessed and bystander CPR. ROSC group showed a higher initial TOI than non-ROSC group (60.5%±17.0% vs 37.9%±13.7%: p<0.01). Area under the curve analysis was more accurate with the initial TOI than without it for predicting ROSC (0.88, 95% CI 0.82 to 0.95 vs 0.79, 95% CI 0.70 to 0.87: p<0.01). TOI cut-off value ≥59% appeared to favour survival to hospital discharge whereas TOI ≤24% was associated with non-ROSC. CONCLUSIONS: This study demonstrated an association between higher initial TOI and ROSC. Initial TOI could increase the accuracy of ROSC prognosis and may be a clinical factor in the decision to terminate CPR and select patients who are to proceed to ECPR.

Efficacy of prehospital National Early Warning Score to predict outpatient disposition at an emergency department of a Japanese tertiary hospital: a retrospective study.

OBJECTIVES: The National Early Warning Score (NEWS) was originally developed to assess hospitalised patients in the UK. We examined whether the NEWS could be applied to patients transported by ambulance in Japan. DESIGN: This retrospective study assessed patients and calculated the NEWS from paramedic records. Emergency department (ED) disposition data were categorised into the following groups: discharged from the ED, admitted to the ward, admitted to the intensive care unit (ICU) or died in the ED. The predictive performance of NEWS for patient disposition was assessed using receiver operating characteristic curve analysis. Patient dispositions were compared among NEWS-based categories after adjusting for age, sex and presence of traumatic injury. SETTING: A tertiary hospital in Japan. PARTICIPANTS: Overall, 2847 patients transported by ambulance between April 2017 and March 2018 were included. RESULTS: The mean (±SD) NEWS differed significantly among patients discharged from the ED (n=1330, 3.7±2.9), admitted to the ward (n=1263, 60.3±3.8), admitted to the ICU (n=232, 9.4±4.0) and died in the ED (n=22, 110.7±2.9) (p<0.001). The prehospital NEWS C-statistics (95% CI) for admission to the ward, admission to the ICU or death in the ED; admission to the ICU or death in the ED; and death in the ED were 0.73 (0.72-0.75), 0.81 (0.78-0.83) and 0.90 (0.87-0.93), respectively. After adjusting for age, sex and trauma, the OR (95% CI) of admission to the ICU or death in the ED for the high-risk (NEWS ≥7) and medium-risk (NEWS 5-6) categories was 13.8 (8.9-21.6) and 4.2 (2.5-7.1), respectively. CONCLUSION: The findings from this Japanese tertiary hospital setting showed that prehospital NEWS could be used to identify patients at a risk of adverse outcomes. NEWS stratification was strongly correlated with patient disposition.

Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo.

Tissue factor (TF) plays a critical role in the pathogenesis of disseminated intravascular coagulation (DIC) observed in patients with septic shock. Urinary trypsin inhibitor (UTI), a multivalent protease inhibitor, is currently used for treatment of patients with septic shock. This study was undertaken to determine whether UTI reduces LPS-induced coagulation abnormalities by inhibiting lipopolysaccharide (LPS)-induced expression of TF by monocytes. UTI inhibited LPS-induced increases in both TF activities and TF mRNA expression in monocytes without affecting the viability. Although activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and extracellular signal-regulated kinase (ERK)1/2 were shown to be critically involved in LPS-induced increases in TF activities in isolated monocytes, UTI inhibited phosphorylation of ERK1/2 and decreased expression of early growth response factor-1 (Egr-1) induced by LPS without affecting the activation of NF-kappaB and AP-1. UTI inhibited both the expression of TF mRNA in whole blood, increases in TF activities in mononuclear cells, and increases in serum levels of fibrin and fibrinogen degradation products (E) in rats given LPS without affecting the number of monocytes in the peripheral blood. Taken together these results strongly suggested that UTI might reduce LPS-induced coagulation abnormalities in rats by inhibiting TF expression in monocytes through inhibition of Egr-1 expression.

Perioperative blood transfusion and survival following curative hepatic resection for hepatocellular carcinoma.

BACKGROUND/AIMS: The association between transfusion and recurrence after resection for hepatocellular carcinoma (HCC) is still under debate. The influences of perioperative blood transfusion on survival and recurrence after curative hepatic resection for HCC and prognostic factors in patients with blood transfusion were evaluated. METHODOLOGY: Curative hepatectomy was performed in 210 patients (57%) with and 158 (43%) without perioperative blood transfusion. Prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that perioperative blood transfusion was an independent predictor for recurrence in patients with serum low albumin level (< 3.5 g/dL). In transfused group, stage IV, large tumor size (> or = 5 cm), high value of ICGR15 (> or = 20%), and old age (> or = 60 year) were independent factors of poor disease-free survival. CONCLUSIONS: Perioperative blood transfusion promotes the recurrence of HCC after hepatic resection in patients with hypo-albuminemia. In transfused patients, establishment of strategy for recurrence based on pTNM staging, tumor size, ICGR15, and age may be required to improve survival.

Longterm prognosis after hepatic resection for small hepatocellular carcinoma.

BACKGROUND: Treatment of small hepatocellular carcinoma (HCC) remains a critical issue. In addition, the longterm prognosis and prognostic factors of small hepatocellular carcinoma after hepatic resection are not well documented. STUDY DESIGN: The surgical outcomes of 135 consecutive patients with one to three HCCs of diameter

A 15-year retrospective study of hepatic resection for stage IV-A hepatocellular carcinoma shows value in hepatitis B negative patients.

BACKGROUND: The aim of this study is to identify the risk factors of survival and recurrence after curative hepatic resection for stage IV-A hepatocellular carcinoma (HCC). METHODS: Sixty-five patients with stage IV-A HCC who underwent curative hepatic resection and discharged from hospital were enrolled in this retrospective study. Prognostic factors were evaluated by univariate and multivariate analysis. Clinicopathologic features and survival with stage IV-A HCC were compared with those of 290 patients with stage I to III HCC who underwent curative hepatic resection during the same period. RESULTS: Disease-free and overall survival for patients with stage IV-A HCC was significantly lower than for those with stage I to III HCC. Positive hepatitis B virus (HBV) surface antigen was an independent prognostic factor of poor disease-free and overall survivals in patients with stage IV-A HCC. There were no significant differences in the disease-free and overall survivals between non-HBV-related stage IV-A HCC and stage I to III HCC. CONCLUSIONS: Even for patients with highly advanced HCC, curative hepatic resection may be a feasible therapeutic option for those with non-HBV-related HCC.

Prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection: univariate and multivariate analysis.

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma is clinicopathologically distinct from hepatocellular carcinoma and hilar cholangiocarcinoma, and the prognostic factors after hepatic resection of these rare tumors are not well documented. The aim of this study was to evaluate prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection. METHODOLOGY: We retrospectively studied 20 consecutive patients with intrahepatic cholangiocarcinoma who underwent hepatectomy over a 15-year period from 1984 to 1998. Fifteen prognostic factors were evaluated for their association with overall and disease-free survivals in univariate and multivariate analysis (Cox's proportional hazards model). RESULTS: Eighty percent of the resected patients had major hepatectomy. Operative morbidity and mortality rates were 30% and 0%, respectively. Four patients (20%) survived more than 5 years without recurrence after hepatic resection. The 1-year, 3-year, and 5-year overall or disease-free survival rate after hepatic resection were 56.0% or 49.5%, 43.8% or 43.3%, and 43.8% or 37.3%, respectively. Univariate analysis showed young age and periductal invasion tumor or the presence of vascular invasion, lymphatic invasion, and lymph node metastasis as significant poor prognostic predictors contributing overall and disease-free survivals. Multivariate analysis revealed only lymph node metastasis as an independent prognostic factor affecting disease-free survival. During the same time, 17 unresectable patients were treated by intrahepatic arterial infusion chemotherapy (12), systemic chemotherapy (4), or radiation (1). Median overall survival time in resected patients (16 months) was significantly better than in unresectable patients (5 months) (P = 0.005). CONCLUSIONS: Hepatic resection remains to be the best current therapeutic option. The prognosis after hepatic resection for intrahepatic cholangiocarcinoma was determined by lymph node metastasis. New adjuvant chemotherapy after surgery is imperative for such patients.

Hepatic resection for hepatocellular carcinoma in diameter of > or = 10 cm.

BACKGROUND/AIMS: Definitive efficacy of hepatic resection for hepatocellular carcinoma larger than or equal to 10 cm in diameter remains to be resolved. METHODOLOGY: The surgical outcomes in 33 consecutive patients with hepatocellular carcinoma in diameter of > or = 10 cm who underwent hepatic resection were retrospectively clarified. Postresection prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: The overall incidence of postoperative complications was 39%, and 5 patients among them had hospital deaths (15%) including 2 (6%) operative deaths. The 3-year, 5-year, and 9-year overall survival rates after hepatic resection were 32%, 27%, and 17%, respectively. Univariate analysis revealed that liver cirrhosis and stage IV-A (pTNM staging) were significant factors of poor overall survival. By Cox's proportional hazards model, liver cirrhosis was an independently unfavorable prognostic factor of long-term survival. Hospital mortality rate in patients with cirrhosis was 31%. The 5-year overall survival rate in patients with cirrhosis (7%) was significantly shorter than that in patients without cirrhosis (43%) (P = 0.006). In addition, the 5-year overall survival rate in patients with stage IV-A (11%) was significantly shorter than that in patients with stage II and III (48%) (P = 0.024). The incidence of stage IV-A in patients with cirrhosis (77%) was significantly higher than those without cirrhosis (35%) (P = 0.032). CONCLUSIONS: Hepatic resection for hepatocellular carcinoma in diameter of > or = 10 cm was effective for patients without liver cirrhosis and with stage II or III. Appropriate selection of the candidates for partial hepatectomy based on the above prognostic factors may play an important role in the improvement of high mortality rate and poor long-term survival for such patients. Prospective randomized trials are needed to define the role of hepatic resection for cirrhotic patients with large HCC.

Cell proliferation, apoptosis and angiogenesis in gastric cancer and its hepatic metastases.

BACKGROUND/AIMS: The levels of cell proliferation, apoptosis and angiogenesis were compared histochemically in gastric cancer and its hepatic metastases. METHODOLOGY: Tissue samples were taken from 7 patients with gastric cancer associated with synchronous and/or metachronous hepatic metastases. In the 7 gastric cancers and in 4 synchronous and 4 metachronous hepatic metastases, Ki-67 immunostaining was performed to measure the labeling index (Ki-67 LI). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling was performed to measure the apoptotic index, and immunostaining for factor VIII-related antigen was performed to measure the microvessel density. RESULTS: The Ki-67 LI was higher in the gastric cancer and the metachronous hepatic metastasis than in the synchronous hepatic metastasis (primary lesions vs. synchronous foci vs. metachronous foci: 47.1% vs. 39.3% vs. 48.0%; P < 0.05). The apoptotic index was lower in the gastric cancer and the metachronous hepatic metastasis than in the synchronous hepatic metastasis (3.50% vs. 5.01% vs. 2.64%; P < 0.05). The microvessel density was higher in the gastric cancer and the metachronous hepatic metastasis than in the synchronous hepatic metastasis (36.0 vs. 22.2 vs. 34.2; P < 0.05). CONCLUSIONS: The present results suggest that tumor growth as indicated by cell proliferation, apoptosis and angiogenesis is less vigorous in synchronous hepatic metastasis than in primary lesion and/or metachronous hepatic metastasis.

AT(1) receptor blockers increase insulin-like growth factor-I production by stimulating sensory neurons in spontaneously hypertensive rats.

Insulin-like growth factor-I (IGF-I) is an important cardioprotective substance. We previously reported that sensory neuron stimulation increases IGF-I production by releasing calcitonin gene-related peptide (CGRP) in spontaneously hypertensive rats (SHRs). Because angiotensin II (Ang II) inhibits sensory neuron activation by interacting with Ang II type 1 (AT(1)) receptors, it is possible that AT(1) receptor blockers (ARBs) increase IGF-I production in SHRs. We examined this possibility in the current study, using the ARBs olmesartan, valsartan, losartan, and telmisartan. Plasma, renal, and cardiac levels of CGRP and IGF-I in SHRs were significantly lower than those in normotensive Wistar Kyoto rats (WKYs) (P < 0.01), which increased to levels found in WKYs after the administration of ARBs. These ARB-induced increases in SHRs were completely reversed by pretreatment with capsazepine (CPZ), which is a specific vanilloid receptor-1 (VR-1) antagonist. The mean arterial blood pressure (MABP) was decreased after administration of ARBs in SHRs, and those decreases were reversed by pretreatment with CPZ. The administration of nifedipine decreased MABP but did not increase CGRP or IGF-I levels in SHRs. Baseline CGRP release and cellular cyclic adenosine 3',5'-monophosphate (cAMP) levels in dorsal root ganglion neurons (DRG) isolated from SHRs were significantly lower than those in DRG isolated from WKYs (P < 0.01). Although ARBs reversed decreases in CGRP release and cAMP levels in the presence of Ang II in DRG isolated from WKYs, they increased CGRP release and cAMP levels in the absence of Ang II in DRG isolated from SHRs. Cellular levels of Ang II were not detected in DRG isolated from WKYs or SHRs, but messenger RNA (mRNA) levels for angiotensin-converting enzyme in DRG were significantly higher in SHRs than in WKYs (P < 0.01). The expression of AT(1) receptors in DRG was not different between WKYs and SHRs. Thus, it is likely that decreases in CGRP release and cAMP levels in DRG isolated from SHRs are mainly caused by AT(1) receptor activation by Ang II through an autocrine mechanism. These observations suggest that ARBs might increase CGRP release from sensory neurons by sensitizing VR-1 activation through increases in cAMP levels, which thereby increased the production of IGF-I in SHRs. These activities of ARBs might at least partly explain their therapeutic effects in areas such as improving insulin resistance in patients with diabetes and hypertension.

Estrogen and isoflavone attenuate stress-induced gastric mucosal injury by inhibiting decreases in gastric tissue levels of CGRP in ovariectomized rats.

We have previously reported that CGRP plays a critical role in the reduction of stress-induced gastric mucosal injury by increasing gastric prostacyclin (PGI(2)) levels in rats. Estrogen has been shown to increase the production of CGRP in sensory neurons. Isoflavone has estrogen-like effects and is referred to as a phytoestrogen. Thus, we hypothesized that estrogen and isoflavone might inhibit ovariectomy (OVX)-induced decreases in gastric tissue levels of CGRP, thereby attenuating gastric mucosal injury. We examined these possibilities in the present study. The administration of estradiol and isoflavone for 4 wk completely reversed OVX-induced decreases in CGRP mRNA levels of dorsal root ganglion neurons (DRGs) in rats. OVX-induced decreases in gastric tissue levels of CGRP and 6-keto-PGF(1alpha), a stable metabolite of PGI(2), in rats were reversed by estradiol and isoflavone. Water-immersion restraint stress (WIR)-induced increases in gastric tissue levels of CGRP and 6-keto-PGF(1alpha) were inhibited in ovariectomized rats. This inhibition was completely reversed by estradiol and was partially, but significantly, reversed by isoflavone. WIR-induced gastric mucosal injury was exacerbated by OVX, which was reversed by estradiol and isofolavone. In vitro experiments using DRGs isolated from rats demonstrated that neither estradiol nor isoflavone enhanced CGRP release from DRGs, but the former enhanced it in the presence of anandamide, an endogenous agonist for vanilloid receptor-1. These observations suggest that estrogen and isoflavone might inhibit OVX-induced decreases in CGRP levels in DRGs by promoting transcription, thereby contributing to the attenuation of stress-induced gastric mucosal injury in OVX rats.

Contribution of sensory neurons to sex difference in the development of stress-induced gastric mucosal injury in mice.

BACKGROUND & AIMS: Sensory neurons play a critical role in reducing stress-induced gastric mucosal injury by releasing calcitonin gene-related peptide (CGRP) through an increase in gastric mucosal levels of prostacyclin (PGI(2)). Because estrogen enhances nerve growth factor-mediated CGRP production in sensory neurons, we hypothesized that stress-induced gastric mucosal injury occurs less in females than in males. METHODS: Gastric ulcer index, gastric myeloperoxidase activity, and gastric tissue levels of CGRP and 6-keto-PGF(1alpha), a stable metabolite of PGI(2), were determined in male and female wild-type (CGRP(+/+)) mice and CGRP knockout (CGRP(-/-)) mice subjected to water-immersion restraint stress. RESULTS: In CGRP(+/+) mice, ulcer index and myeloperoxidase activities were lower and gastric tissue levels of CGRP and 6-keto-PGF(1alpha) were higher in female mice than in male mice, but there were no such sex differences in CGRP(-/-)mice. Sex differences in CGRP(+/+) mice were eliminated by pretreatment with SB366791 (500 microg/kg intraperitoneally), a vanilloid receptor antagonist, and by ovariectomy. Reversal of sex differences by ovariectomy was not observed in female CGRP(+/+) mice with estradiol replacement (1 mg . kg(-1). wk(-1) for 3 weeks). Levels of CGRP messenger RNA in dorsal root ganglion neurons isolated from female CGRP(+/+) mice were decreased by ovariectomy, and these decreases were reversed by estradiol replacement. CONCLUSIONS: Estrogen-mediated increases in CGRP levels in sensory neurons might contribute to reduce stress-induced gastric mucosal injury by attenuating inflammatory responses. This might at least partly explain the sex difference observed in the development of stress-induced gastric mucosal injury in mice.