Changes in alcohol intake and serum urate changes: longitudinal analyses of annual medical examination database.

INTRODUCTION: Despite the established cross-sectional association between alcohol intake and serum urate (SU), its longitudinal association remains unknown. This study aimed to determine whether changes in alcohol intake have a clinically relevant association with SU change. METHOD: We conducted retrospective analyses using systematically collected annual medical examination data from October 2012 to October 2022 in a Japanese preventive medicine centre. The exposure was changes in alcohol intake between two consecutive visits. The association of SU changes with alcohol intake changes was estimated by mixed-effect linear regression with adjustment for relevant covariates. RESULTS: We analysed 63 486 participants (median age, 47.0 years; 55% women; 58.6% regular alcohol drinkers with a median of 1.4 drinks/day) with 370 572 visits. The median SU level was 5.3 mg/dL, and 506 (0.8%) participants had diagnoses of gout or hyperuricemia without medication use during the study period. Decreasing one daily alcohol intake had a clinically small association with SU changes (-0.019 (95% CI: -0.021 to -0.017) mg/dL). Beer had the largest association with SU (-0.036 (95% CI: -0.039 to -0.032) mg/dL for one beer decrease). Complete discontinuation of any alcohol from a mean of 0.8 drinks/day was associated with -0.056 mg/dL (95% CI: -0.068 to -0.043) decrease in SU; the association became larger in hyperuricemic participants (-0.110 mg/dL (95% CI: -0.154 to -0.066) for alcohol discontinuation from a mean of 1.0 drinks/day). CONCLUSIONS: This study revealed changes in alcohol intake had small associations with SU change at the general Japanese population level. Complete discontinuation of alcohol in hyperuricemic participants had only modest improvement in SU.

Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content.

Importance: Differences have been observed in the association of serum urate levels with consumption of different types of alcoholic beverages. However, previous studies have not standardized the unit of intake for ethanol content, and only limited types of alcoholic beverages have been evaluated. Objective: To examine differences in the association of serum urate levels with various types of alcoholic beverages when their intakes are standardized for ethanol content. Design, Setting, and Participants: This retrospective cross-sectional study was conducted using data from participants aged 20 years or older who completed a medical checkup at St Luke's International University in Japan between October 1, 2012, and October 31, 2021. Participant demographics, blood test results, and lifestyle questionnaire data were used as covariates. Analysis was performed in December 2021. Exposures: Consumption of alcoholic beverages, including beer, sake (rice wine), shochu (Japanese spirit), wine, and whiskey. Main Outcomes and Measures: Serum urate levels were measured during the medical checkup. The beverage unit was standardized to 1 standard drink, which contained 20 g of ethanol. Multivariable linear regression including interaction terms of alcohol consumption and dominant alcoholic beverage was performed. Results: This study included 78 153 participants. Their mean (SD) age was 47.6 (12.8) years; 36 463 (46.7%) were men and 41 690 were women (53.3%). A total of 45 755 participants (58.5%) were regular alcohol drinkers. Consistent associations of serum urate levels with alcohol consumption were observed in the beer-dominant group, with ß coefficients (for 1 standard drink per day) of 0.14 mg/dL (95% CI, 0.11-0.17 mg/dL; P < .001) for men and 0.23 mg/dL (95% CI, 0.20-0.26 mg/dL; P < .001) for women. A moderate increase in serum urate levels was observed in the wine-dominant group compared with a modest and nonsignificant increase in the sake-dominant group, with ß coefficients (for 1 standard drink per day) for the latter group of 0.05 mg/dL (95% CI, -0.01 to 0.10; P = .10) for men and 0.04 mg/dL (95% CI, -0.05 to 0.14 mg/dL; P = .38) for women. Restricted cubic splines showed different patterns in associations of serum urate levels with ethanol intake by dominant alcoholic beverages. Conclusions and Relevance: The results of this study suggest that the extent of the association of serum urate levels with alcohol intake was different for alcoholic beverages even after ethanol content was standardized. Higher beer consumption among men and women was consistently associated with higher serum urate levels, whereas sake was not associated with changes in serum urate levels. Therefore, alcoholic beverage type, in addition to ethanol content, should be considered as a factor contributing to hyperuricemia.

Modification of the immune response by bacteriophages alters methicillin-resistant Staphylococcus aureus infection.

There is an urgent need to develop phage therapies for multidrug-resistant bacterial infections. However, although bacteria have been shown to be susceptible to phage therapy, phage therapy is not sufficient in some cases. PhiMR003 is a methicillin-resistant Staphylococcus aureus phage previously isolated from sewage influent, and it has demonstrated high lytic activity and a broad host range to MRSA clinical isolates in vitro. To investigate the potential of phiMR003 for the treatment of MRSA infection, the effects of phiMR003 on immune responses in vivo were analysed using phiMR003-susceptible MRSA strains in a mouse wound infection model. Additionally, we assessed whether phiMR003 could affect the immune response to infection with a nonsusceptible MRSA strain. Interestingly, wounds infected with both susceptible and nonsusceptible MRSA strains treated with phiMR003 demonstrated decreased bacterial load, reduced inflammation and accelerated wound closure. Moreover, the infiltration of inflammatory cells in infected tissue was altered by phiMR003. While the effects of phiMR003 on inflammation and bacterial load disappeared with heat inactivation of phiMR003. Transcripts of proinflammatory cytokines induced by lipopolysaccharide were reduced in mouse peritoneal macrophages. These results show that the immune modulation occurring as a response to the phage itself improves the clinical outcomes of phage therapy.

Epidemiology of bloodstream infections and surface swab cultures in burn patients.

Aim: For infection control in burn patients, it is essential to understand the epidemiology of bloodstream infection (BSI) and the local microbiological situation. There are few studies on blood and swab culture results among burn patients in Japan. The purpose of this study was to investigate the epidemiology of BSI and swab cultures in burn patients. Methods: Data from 355 burn patients over 13 years from 2008 were analyzed retrospectively. Bloodstream infection was defined as the isolation of bacteria or fungi from two or more blood cultures. The characteristics of burn patients and microorganisms detected from various cultures were analyzed. Results: The mortality rate among burn patients with BSI was 37.8%, which was more than twice that among burn patients without BSI. The univariate analysis showed that inhalation injury, total burn surface area (TBSA), and mortality were associated with BSI. The multivariate logistic analysis indicated that TBSA was an independent risk factor for BSI. The most frequently isolated organism from blood and swab cultures were Candida species and Pseudomonas aeruginosa, respectively. Seventy-five percent of the microorganisms isolated from blood were detected previously in swab cultures performed within 1 week from blood cultures. Conclusions: The prognosis of burn patients with BSI was poor, and TBSA was an independent risk factor for BSI. The predominant organisms isolated from blood and swab cultures were Candida species and P. aeruginosa, respectively. Surveillance wound swab cultures could be utilized for monitoring the local microbiological situation in burn patients.

Clinical impact of noncontrast percutaneous coronary intervention in patients with acute coronary syndrome.

PURPOSE: Contrast-induced acute kidney injury (CI-AKI) is one of the common serious complications of percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). This study aimed to assess the significance of noncontrast strategy in the setting of ACS. METHODS: CI-AKI was defined as an increase in serum creatinine of ?0.5 mg/dL or ?1.25 times from the baseline. One-year worsening renal function (WRF) was defined as an increase of ?0.3mg/dL in serum creatinine from the baseline after PCI. RESULTS: Of 250 ACS patients, 81 were treated with noncontrast PCI. The average doses of contrast medium in the noncontrast and conventional groups were 17 (9?22) ml and 150 (120?200) ml, respectively. CI-AKI was observed in 4 patients (5%) in the noncontrast group and 29 patients (17%) in the conventional group. Noncontrast PCI was associated with a lower incidence of CI-AKI (adjusted odds ratio, 0.26;95% confidence interval [CI], 0.08?0.82). The bootstrap method and inverse probability weighting led to similar results. CI-AKI was associated with a higher incidence of 1-year WRF (adjusted hazard ratio, 2.30;95% CI, 1.12?4.69), while noncontrast PCI was not. CONCLUSIONS: Noncontrast PCI was associated with the lower incidence of CI-AKI in ACS patients. J. Med. Invest. 69 : 57-64, February, 2022.

Clinical impact of perioperative atrial fibrillation on long-term recurrence of malignancy.

Perioperative complications have been reported to be associated with a lower incidence of cancer-free survival. Perioperative atrial fibrillation (POAF) is one of occasionally observed complications in patients with malignancies who undergo noncardiac surgeries. However, the long-term clinical impact of POAF on those with malignancies have remained unknown. This was a prospective, single-center, observational study. Patients who underwent noncardiac surgeries for definitive malignancies between 2014 and 2017 were included. The primary and secondary endpoints were 3-year recurrence of malignancies and cancer death, respectively. The present study included consecutive 752 patients (mean age, 68 ± 11 years; males, 62%), and POAF was observed in 77 patients. The follow-up duration was 1037 (interquartile range, 699-1408) days. The 3-year recurrence of malignancies was observed in 239 (32%) patients (POAF, 32 [42%]; non-POAF, 207 [31%]) and 3-year mortality was 130 patients (17%). Cardiac, noncardiac, and cancer deaths were observed in 4 (0.5%), 126 (17%), and 111 (15%) patients, respectively. Multivariate Cox regression analysis demonstrated that POAF was associated with 3-year recurrence of malignancies (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.15-2.52). Landmark analysis demonstrated that POAF tended to be correlated with the incidence of 3-year cancer death (HR, 1.79; 95% CI, 0.96-3.31). In conclusion, POAF is associated with the subsequent recurrence of malignancies. The association of arrhythmia with cancer death may be revealed under longer follow-up durations.Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018270 . UMIN ID: UMIN000016146.

Clinical impact of red blood cell transfusion on adverse clinical events in acute heart failure patients with anemia.

BACKGROUND: Anemia has been recognized as an important comorbidity in patients with acute heart failure (AHF) and is associated with adverse clinical events. However, the clinical impact of red blood cell (RBC) transfusion in such patients is unclear. METHOD: This study was a retrospective single-center registry including AHF patients admitted to Kyorin University Hospital between 2007 and 2014. Anemia was defined as a hemoglobin level < 130 g/L in males or < 120 g/L in females. Those with major bleeding with a fall in hemoglobin concentration of >20 g/L were excluded. AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were evaluated. RESULTS: Of 501 AHF patients, 38 were excluded owing to major bleeding; finally, 463 (age, 77 ± 11 years; males, 58%) were evaluated. RBC transfusion during hospitalization was performed in 112 patients (24%). Hemoglobin level on admission was 105 ± 16 g/L (transfusion, 89 ± 17 g/L; no transfusion, 110 ± 12 g/L; p < 0.001). AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were observed in 46 (10%), 16 (3%), and 121 (26%) patients, respectively. Univariate Cox regression analysis demonstrated that RBC transfusion was not associated with AHF readmission at 3 months (hazard ratio: 0.80; 95% confidence interval: 0.39-1.66) The association did not differ at any hemoglobin concentration or left ventricular ejection fraction value. Multivariate Cox regression analysis revealed similar results. Furthermore, RBC transfusion was not correlated with in-hospital and 2-year all-cause mortality. CONCLUSIONS: RBC transfusion was not associated with AHF readmission or all-cause mortality.

Skin and Soft Tissue Infections Caused by Different Genotypes of PVL-Positive Community-Acquired Methicillin-Resistant Staphylococcus aureus Strains.

Panton-Valentine leukocidin (PVL) is a causative agent of lethal necrotizing pneumonia and is associated with epidemic strains of community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA). PVL-producing strains have rarely been isolated in Japan. However, PVL-positive CA-MRSA has been isolated much more frequently in recent years. To investigate the relevance of pvl genes (lukS/F-PV) and clinical traits in epidemic S. aureus strains, we genotyped four PVL-positive CA-MRSA strains isolated from patients with skin and soft tissue infections and measured their susceptibility to antibiotics. Three of the isolates matched the genotype of the USA300 clone, which has predominantly been isolated in the USA. The remaining strain matched the ST217 genotype, and its spa type was identical to that of PVL-positive strains previously reported in India and China. Abscess drainage was necessary in all cases, and deep cutaneous ulcers were formed in three out of four cases regardless of the genotype. The ST217 genotype strain was resistant to clindamycin, in addition to quinolones, macrolides, and aminoglycosides. Thus, diagnostic determination of lukS/F-PV should be used as a guide for selecting the treatment regimen.

Silviavirus phage ɸMR003 displays a broad host range against methicillin-resistant Staphylococcus aureus of human origin.

The emergence of life-threatening methicillin-resistant Staphylococcus aureus (MRSA) has led to increased interest in the use of bacteriophages as an alternative therapy to antibiotics. The success of phage therapy is greatly dependent on the selected phage possessing a wide host range. This study describes phage ɸMR003 isolated from sewage influent at a municipal wastewater treatment plant in Tokyo, Japan. ɸMR003 could infect 97% of 104 healthcare- and community-associated MRSA strains tested, compared with 73% for phage ɸSA012, which has a broad host range against bovine mastitis S. aureus. Genome analysis revealed that ɸMR003 belongs to the genus Silviavirus which has not been studied extensively. ɸMR003 recognizes and binds to wall teichoic acid (WTA) of S. aureus during infection. In silico comparisons of the genomes of ɸMR003 and ɸSA012 revealed that ORF117 and ORF119 of ɸMR003 are homologous to the putative receptor-binding proteins ORF103 and ORF105 of ɸSA012, with amino acid similarities of 75% and 72%, respectively. ORF104, which is an N-acetylglucosaminidase found in the ɸMR003 tail, may facilitate phage's infection onto the WTA-null S. aureus RN4220. The differences in tail and baseplate proteins may be key contributing factors to the different host specificities of ɸMR003 and ɸSA012. ɸMR003 showed strong adsorptivity, but not infectivity, against S. aureus SA003, which may be influenced by the bacterium's restriction modification system. This study expands our knowledge of the genomic diversity and host specificity of Silviavirus, which is a potential phage therapy candidate for MRSA infections.

Sufficient therapeutic effect of cryopreserved frozen adipose-derived regenerative cells on burn wounds.

INTRODUCTION: The purpose of this study was to evaluate whether cryopreserved (frozen) adipose-derived regenerative cells (ADRCs) have a therapeutic effect on burn wound healing as well as freshly isolated (fresh) ADRCs. METHODS: Full thickness burns were created on dorsum of nude mice and burn wound was excised. The wound was covered by artificial dermis with; (i) fresh ADRCs, (ii) frozen ADRCs, and (iii) PBS (control). The assessment for wound healing was performed by morphological, histopathological and immunohistochemical analyses. RESULTS: In vivo analyses exhibited the significant therapeutic effect of frozen ADRCs on burn wound healing up to the similar or higher level of fresh ADRCs. There were significant differences of wound closure, epithelized tissue thickness, and neovascularization between the treatment groups and control group. Although there was no significant difference of therapeutic efficacy between fresh ADRC group and frozen ADRC group, frozen ADRCs improved burn wound healing process in dermal regeneration with increased great type I collagen synthesis compared with fresh ADRCs. CONCLUSIONS: These findings indicate that frozen ADRCs allow us to apply not only quickly but also for multiple times, and the cryopreserved ADRCs could therefore be useful for the treatment of burn wounds in clinical settings.

Independent risk factors for a complicated hospital course in intensive care unit overdose patients.

Aim: The purpose of the present study was to identify risk factors associated with a complicated hospital course in overdose patients admitted to the intensive care unit. Methods: A total of 335 overdose patients were retrospectively studied in the surgical and medical intensive care unit of an academic tertiary hospital. Factors possibly associated with a complicated hospital course were evaluated. Complicated hospital course was defined as the occurrence of pneumonia, rhabdomyolysis, decubitus ulcer, nerve palsy, prolonged intubation, prolonged hospitalization, or death. Results: Of the 335 overdose patients, 93 (27.8%) had a complicated hospital course. Complicated hospital course was found to be associated with a high number of ingested pills (median, 135 [interquartile range, 78-240] versus 84 [53-134] tablets, P < 0.0001), low Glasgow Coma Scale score on admission (7 [3-11] versus 13 [8-15], P < 0.0001), and a high serum lactate level on admission (1.8 [1.0-3.0] versus 1.4 [0.9-2.0] mg/dL, P < 0.01) on univariate analysis of these factors in patients with and without a complicated hospital course. The independent risk factors for a complicated hospital course identified on multivariate analysis were a high number of ingested pills (≥100 tablets), low admission Glasgow Coma Scale score (<9), and high serum lactate on admission (≥2.0 mg/dL). The probability of a complicated hospital course for patients with 0, 1, 2, or all 3 independent risk factors were 7%, 22%, 40%, and 81%, respectively. Conclusion: The total number of ingested pills, admission Glasgow Coma Scale score, and serum lactate level on admission are predictive of a complicated hospital course in overdose patients admitted to the intensive care unit.

[Emergency care of vertigo patients: suggestions for efficient management].

Some diseases in which persons show vertigo or dizziness may be life-threatening, regardless of symptom severity, and require careful attention. These include diseases of the inner ear, central nervous system, and cardiovascular manifestation. In May 2006, a group in charge of primary emergency consultation began work enabling physicians to treat vertigo patients more efficiently and safely, as detailed in this report. Of the 173 persons with vertigo hospitalized from January 2004 to March 2008, six had cerebrovascular manifestations clarified only after hospitalization, underscoring the importance of careful examination, especially of those 75 years of age older, having continuous headache, having severe trunk ataxia despite apparently mild eye nystagmus, or reporting a history of high blood pressure, diabetes mellitus, hyperlipidemia, or ischemic heart disease.

Life-threatening subcutaneous hemorrhage following minor blunt trauma in an elderly patient taking ticlopidine and aspirin: a case report.

We report a rare case in which life-threatening subcutaneous hemorrhage following minor blunt trauma developed in an elderly patient taking ticlopidine and aspirin. An 82-year-old woman taking ticlopidine and aspirin tripped on a road. She noted only mild pain at the left lower abdomen. However, the hematoma gradually enlarged, and she developed hemorrhagic shock. Emergently performed contrast-enhanced abdominal computed tomography showed a large hematoma (20 x 10 x 7 cm), including contrast extravasation, which was located beneath the skin of the left lower abdominal quadrant and within the external and internal oblique muscles. Emergency pelvic arteriography showed massive contrast extravasation from the left superficial iliac circumflex artery. Transcatheter arterial embolization (TAE) was successfully performed, using gelatin sponge pledgets and micro-size stainless steel coils. After TAE, hemodynamics stabilized. The patient was discharged uneventfully on day 12.

Relationship between pseudoaneurysm formation and biloma after successful transarterial embolization for severe hepatic injury: permanent embolization using stainless steel coils prevents pseudoaneurysm formation.

OBJECTIVE: The purpose of this study was to determine the association between bilomas and pseudoaneurysm complications after severe hepatic injury. METHODS: Angiography was performed in patients with American Association for the Surgery of Trauma grade > or = III hepatic injury on contrast-enhanced computed tomographic scanning. When contrast extravasation was observed, transarterial embolization (TAE) was performed. After TAE, technetium-99m pyridoxyl-5-methyl-tryptophan cholescintigraphy was performed to detect the coexistence of bilomas. Follow-up angiography was performed when a biloma was detected. Eighty consecutive patients underwent angiography; after angiography, five patients died. The remaining 75 patients who underwent cholescintigraphy were included in this study. RESULTS: All 11 patients who had bilomas had angiographic evidence of contrast extravasation. The biloma frequency was higher in patients with grades IV and V injuries than in those with grade III injury (p = 0.024). Follow-up angiography revealed pseudoaneurysms in 7 of these 11 patients. All six patients in whom only gelatin sponge pledget injection was used to embolize had pseudoaneurysms. Among them, two patients had computed tomographic evidence of massive intra-abdominal fluid collection. In contrast, only one of five patients who received the combination of gelatin sponge pledget injection and stainless steel coils to permanently embolize injured arteries had a pseudoaneurysm. In this patient, the pseudoaneurysm was found in the peripheral part of the collateral vessels. All patients with pseudoaneurysms underwent repeat TAE and were discharged from the hospital uneventfully. CONCLUSION: In patients with high-grade hepatic injury and arterial bleeding who developed biloma, use of a gelatin sponge, an absorbable embolic material, is associated with a risk of pseudoaneurysm formation. Permanent arterial embolization using stainless steel coils is indicated to decrease this risk.

Lysis-deficient bacteriophage therapy decreases endotoxin and inflammatory mediator release and improves survival in a murine peritonitis model.

BACKGROUND: Lysis-deficient (LyD) bacteriophages (phages) kill bacteria without endotoxin (Et) release. This may minimize systemic cytokine responses and limit inflammation in bacterial sepsis. We determined the effects of t amber A3 T4 LyD and virulent wild-type (WT) phages on mouse bacterial peritonitis. METHODS: Balb/c mice were injected with B40sul Escherichia coli, treated intraperitoneally with LyD, WT, or a beta-lactam antibiotic [latamoxef sodium (LMOX)], and followed for survival. We measured Et release, tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, as well as bacterial counts and peritoneal exudative cells (PECs) in peritoneal lavage fluid at 6 and 12 hours after infection. RESULTS: LyD mice showed significantly greater survival compared with other groups. Et levels were significantly lower in the LyD mice at 6 and 12 hours after infection. TNF-alpha and IL-6 levels were lower in LyD mice compared with control (untreated) mice at 12 hours. Compared with controls, bacteria counts in peritoneal lavage fluid were lower in all treatment groups (LyD, WT, or LMOX) at 6 and 12 hours. PEC counts were highest in LyD mice at 6 hours but significantly lower than that in WT phage- and LMOX-treated mice at 12 hours. CONCLUSIONS: LyD phage therapy significantly improves survival and attenuates the systemic effects of bacterial sepsis by minimizing Et release and pro-inflammatory mediators in murine bacterial peritonitis. Further studies may find phage therapy useful in treating peritonitis and multidrug-resistant bacterial infections.

The usefulness of transcatheter arterial embolization for patients with blunt polytrauma showing transient response to fluid resuscitation.

BACKGROUND: This study aimed to determine whether nonsurgical management using transcatheter arterial embolization (TAE) is safe for patients with blunt multiple trauma who transiently respond to the initial fluid resuscitation. METHODS: Contrast computed tomography was performed for patients with blunt abdominal injuries, excluding those who did not respond to initial fluid resuscitation. Angiography was performed for patients with injuries showing contrast extravasation or solid organ injury classified, according to the American Association for the Surgery of Trauma, as grade 3 or higher on computed tomography. Transcatheter arterial embolization was performed when angiography showed arterial extravasation. The protocol was abandoned for any patients who became profoundly hypotensive (with systolic blood pressure 60 mm Hg or lower) during computed tomography or angiography. RESULTS: Between January 2000 and December 2002, 269 patients with blunt abdominal injuries underwent TAE immediately after admission. Of these patients, 41 had injuries in at least two regions and underwent TAE for these regions. Among them, 22 patients were hemodynamically stable or showed rapid response to fluid resuscitation. The nonsurgical treatment was successful in all these cases. The remaining 19 patients (Injury Severity Score, 37.3 +/- 8.2), who showed a transient response, were the subjects of this study. Of these patients, 15 underwent TAE for injuries in two regions (13 pelvic fractures, 7 splenic injuries, 6 hepatic injuries, 3 facial bleeding, and 1 renal injury), and 4 patients underwent TAE for injuries in three regions (4 had splenic injuries, 3 hepatic injuries, 2 renal injuries, 2 pelvic fractures, and 1 facial bleeding). For all these patients, TAE was successfully performed. Before TAE, the systolic blood pressure was 79.9 +/- 8.4 mm Hg, and the shock index was 1.45 +/- 0.25 mm Hg. After TAE, the corresponding values were 120.6 +/- 19.3 mm Hg and 0.87 +/- 0.16 mm Hg, respectively (p < 0.001). The rate of fluid administration required after TAE (214.2 +/- 139.3 mL/hour) was significantly less than that required before TAE (1244.2 +/- 347.1 mL/hour; range, 632-1,728 mL/hour) (p < 0.001). The deaths of two patients were classified as nonpreventable on the basis of the Trauma and Injury Severity Score (TRISS), and their respective probabilities of survival were determined to be 0.13 and 0.03. CONCLUSION: Nonsurgical management using TAE can be performed safely even for patients with blunt multiple trauma who are in hemorrhagic hypotension if their hemodynamics are improved by resuscitation with 2 L of fluid.

NS-398 inhibits tumor growth and liver metastasis of colon cancer through induction of apoptosis and suppression of the plasminogen activation system in a mouse model.

BACKGROUND: Cyclooxygenase-2 (COX-2) is overexpressed in colon cancers. The plasminogen activation (PA) system relates to cancer invasion and metastasis through the degradation of the extracellular matrix. COX-2 also relates to degradation of the extracellular matrix, but the relationship between COX-2 and the plasminogen activator system is unclear. STUDY DESIGN: In vivo: Colon 38 (G0) primary and (G5) metastatic cell lines were implanted in C57BL/6 mice treated with or without COX-2 inhibitor (NS-398). Animal survival and tumor growth were measured. On day 19, tumors were excised and tumor cell apoptosis measured. For metastasis, G5 cells were injected into the spleen, and, after 23 days, liver metastasis was determined. In vitro: G0 or G5 cells were treated with NS-398. Supernatant prostaglandin E2 and mRNA expressions of COX-2, vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (u-PA), u-PA receptor, plasminogen activator inhibitor type-1 (PAI-1), and PAI-2 were measured. Tumor cell proliferation was also determined. RESULTS: In vivo: Mean survival of NS-398-treated animals was higher than controls for both G5 and G0 (G5: p < 0.003, G0: p < 0.02). G5 tumors grew faster than G0 tumors (p < 0.001) and NS-398 significantly inhibited tumor growth (p < 0.001), induced tumor cell apoptosis (p < 0.001), and significantly reduced metastasis (p < 0.003) in G5 animals. In vitro: PGE(2) production was higher in G5 than G0 cells (p < 0.001); NS-398 significantly reduced prostaglandin E(2) levels in G5 cells (p < 0.001). mRNA expression of COX-2, vascular endothelial growth factor, and u-PA receptor was higher in G5 than G0 cells, and NS-398 significantly inhibited u-PA mRNA expression in G5 cells. NS-398 significantly reduced proliferation in G5 cells (p < 0.05). CONCLUSIONS: COX-2 inhibition significantly decreases tumor growth in this model by inducing apoptosis and blocking u-PA production in G5 colon cancer cells, which is associated with significant inhibition of liver metastases.