ライフサイエンスコーパス: HUS

1 HUS is responsible for most deaths associated with E. co

2 HUS is similar to TTP, but is associated with acute rena

3 HUS is usually categorized as typical, caused by Shiga t

4 HUS was the primary outcome.

5 HUS-1 is required for genome stability, as demonstrated

6 oses (n = 11) exceeded the MTCD because of 2 HUS/TMA/HUS-like events.

7 Compared with waitlisted adult HUS patients on dialysis, 5-year mortality risks were 73

8 We retrospectively studied adult-HUS end-stage renal disease patients (n = 559) placed on

9 n the intermediate outcome in children after HUS due to E. coli O104:H4 have been lacking.

10 overall outcome of pediatric patients after HUS due to E. coli O104:H4 was equivalent to previous re

11 xcellent candidate for immunotherapy against HUS and that antibodies directed against the A subunit o

12 at provide cost-effective protection against HUS opens up new therapeutic approaches to managing dise

13 SpHUS accounts for 5-15% of all HUS cases.

14 ucture revealing that the N-terminal DCB and HUS regulatory domains of the Arf-GEF Sec7 form a single

15 Bloody diarrhea and HUS were recorded as the most severe outcome for 44 and

16 ains, including strains isolated from HC and HUS cases.

17 57:H7 resulted in higher hospitalization and HUS rates than previous STEC outbreaks.

18 evelopment of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical mo

19 idence of pediatric HUS, which is defined as HUS in children <18 years.

20 n dysregulation preceded HUS and worsened as HUS developed.

21 Diarrhea-associated HUS accounts for more than 90% of cases and is usually c

22 et and fibrin thrombi in diarrhea-associated HUS.

23 pediatric patients with diarrhea-associated HUS.

24 As with CFH- and MCP-associated HUS, there was incomplete penetrance in the family of on

25 ly no specific therapies for STEC-associated HUS, and the mechanism of Stx-induced renal injury is no

26 Atypical HUS (aHUS) can result from genetic or autoimmune factors

27 Atypical HUS (aHUS) is a disorder most commonly caused by inherit

28 Atypical HUS is frequently a diagnosis of exclusion.

29 cherichia coli (STEC) infection, as atypical HUS (aHUS), usually caused by uncontrolled complement ac

30 tudy provides further evidence that atypical HUS is a disease of complement dysregulation.

31 or protein (MCP;CD46) predispose to atypical HUS (aHUS), which is not associated with exposure to Shi

32 ent and inflammation, predispose to atypical HUS, we assessed whether impaired TM function may advers

33 ess complement activation underlies atypical HUS and is evident in Shiga toxin-induced HUS (STEC-HUS)

34 er-increasing number of associations between HUS and a variety of drugs.

35 clude some of the newer associations between HUS and a variety of infections, including, but not limi

36 aware that STEC, other than O157, can cause HUS, and 34% correctly interpreted a positive Shiga toxi

37 equently produced by STEC strains that cause HUS than is Stx1a.

38 Shiga toxin 2 are much more likely to cause HUS than are those that produce Shiga toxin 1 alone.

39 t contribute to an enhanced ability to cause HUS.

40 uman primates (Papio) recapitulated clinical HUS after Stx challenge and that novel therapeutic inter

41 tric series of Shiga toxin-producing E. coli HUS.

42 ame disease process, whereas others consider HUS and TTP to be distinct clinical and pathologic entit

43 at express Stx2 are more likely to cause D(+)HUS than are E coli expressing only Stx1.

44 ea-associated hemolytic uremic syndrome (D(+)HUS) is caused by the ingestion of Escherichia coli that

45 ible exception of Shiga toxin-mediated HUS(D+HUS), long-term outcome information is often limited by

46 Renal damage in D+HUS is caused by Shiga toxin (Stx), which is elaborated

47 post-diarrheal hemolytic-uremic syndrome (D+HUS) is related to shigatoxin (Stx) binding to globotria

48 rhea-associated hemolytic uremic syndrome (D+HUS) is the most common cause of acute renal failure amo

49 ic purpura, a disease with similarities to D+HUS, in Adamts13(-/-) mice.

50 We find that the DCB/HUS domain amplifies the ability of Sec7 to activate Arf

51 he 259 children analyzed, 36 (14%) developed HUS.

52 men, 22 (92%) were adults, 7 (29%) developed HUS, 5 (21%) developed bloody diarrhea, and 12 (50%) dev

53 the diarrhea phase more frequently developed HUS than those who did not (36% vs 12%; P = .001).

54 A case was an attendee who developed HUS or diarrhea between 8 and 24 June.

55 who received antibiotics, (3) who developed HUS, and (4) for whom data reported timing of antibiotic

56 diarrhea (odds ratio = 1.81) and developing HUS (odds ratio = 1.83) than did men.

57 ther established risk factors for developing HUS, such as Shiga toxin 2 and EHEC serotypes traditiona

58 nd/or individuals at high risk of developing HUS due to exposure to STEC.

59 lly protected against the risk of developing HUS.

60 ociated with an increased risk of developing HUS; however, after excluding studies at high risk of bi

61 nding of the pathogenetic mechanisms driving HUS has increased.

62 ion is profoundly affected before and during HUS, reflecting that subclinical endothelial dysfunction

63 ophils and monocytes as the key event during HUS development.

64 macrophages were evaluated in an established HUS mouse model.

65 for microvascular thrombosis in experimental HUS.

66 t behind the acute renal failure of familial HUS patients.

67 erve as a marker of a greater propensity for HUS, similar to the correlation between the absence of s

68 n the absence of stx(1) and a propensity for HUS.

69 s (Stx1, Stx2) are primarily responsible for HUS and the kidney and neurologic damage that ensue.

70 ation during STEC infections on the risk for HUS.

71 Currently, specific therapeutics for HUS are lacking, and therapy for patients is primarily s

72 argets and development of new treatments for HUS is described.

73 t produce only Stx1 are rarely isolated from HUS cases.

74 of ADAMTS13 activity distinguishes TTP from HUS and other types of thrombotic microangiopathy (TMA);

75 However, SNPs from the IL12A, HUS, CYP2C8 genes were associated with time to anemia, a

76 of p38 MAPK may be of therapeutic benefit in HUS.

77 Differences in HUS frequency among E. coli O157:H7 outbreaks have been

78 /Ang-1 ratio were significantly different in HUS vs the pre-HUS phase of illness or uncomplicated inf

79 ed RBC-derived microvesicles are elevated in HUS patients and induced in vitro by incubation of RBCs

80 ar transplantation probability was higher in HUS than in DM and HTN patients.

81 neutrophil/platelet aggregates) involved in HUS pathogenesis.

82 associated with podocyte damage and loss in HUS mice generated by the coinjection of Stx2 and LPS.

83 Activated neutrophils are observed in HUS patients, yet it is unclear whether Stx exerts a dir

84 Shiga toxins (Stx) play a pivotal role in HUS by triggering endothelial damage in kidney and brain

85 al HUS and is evident in Shiga toxin-induced HUS (STEC-HUS).

86 E. coli O104:H4 caused the largest HUS outbreak in children reported in detail to date and

87 Complement mediated HUS (aHUS) has a worse prognosis compared with shiga tox

88 prognosis compared with shiga toxin mediated HUS, often resulting in end stage renal disease.

89 e possible exception of Shiga toxin-mediated HUS(D+HUS), long-term outcome information is often limit

90 ed to E. coli 0157:H7 (Shiga toxin-mediated) HUS, as well as the ever-increasing number of associatio

91 Diarrhea-negative HUS is associated with complement dysregulation in up to

92 uration (median, 13-14 days) compared to non-HUS patients (median, 33-34 days).

93 STEC O111 accounted for most cases of HUS and was also the cause of 3 of 7 non-O157 STEC outbr

94 oli O157:H7 remains the predominant cause of HUS in our institution.

95 ases platelet aggregation, in the context of HUS.

96 In addition, a time course of HUS disease progression that will be useful for identifi

97 venous fluid administration up to the day of HUS diagnosis was associated with a decreased risk of re

98 those employing an appropriate definition of HUS yielded an OR of 2.24 (95% CI, 1.45-3.46; I(2) = 0%)

99 t did not employ an acceptable definition of HUS, there was a significant association.

100 antibiotic administration and development of HUS was 1.33 (95% confidence interval [CI], .89-1.99; I(

101 Development of HUS, complications (ie, oligoanuric renal failure, invol

102 independently associated with development of HUS.

103 tory response involved in the development of HUS.

104 tric patients with the clinical diagnosis of HUS were registered in Austria and Germany, and a subset

105 uid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation.

106 Renal failure is a key feature of HUS and a major cause of childhood renal failure worldwi

107 or presumed STEC infection, and some form of HUS that developed.

108 g the pathogenesis of the different forms of HUS may prove helpful in clinical practice.

109 iga toxin mediated and the atypical forms of HUS, with a focus on genetic variations in the complemen

110 inach, there was a notably high frequency of HUS.

111 Management of HUS remains supportive; there are no specific therapies

112 nfected outpatients without manifestation of HUS, were investigated between May 15 and July 26, 2011,

113 osystem can function as an in vitro model of HUS and showed that shear stress influences microvascula

114 We have developed a mouse model of HUS by administering endotoxin-free Stx2 in multiple dos

115 A mouse model of HUS designed to mirror human mutations in FH has now bee

116 at this C57BL/6 mouse is a complete model of HUS that includes the thrombocytopenia, hemolytic anemia

117 he contribution of CCR1 in a murine model of HUS.

118 the frequency of bloody diarrhea but not of HUS and the length of the incubation period depended on

119 dy their efficacy in preventing the onset of HUS during the systemic blood phase of Stx.

120 type have been linked to the pathogenesis of HUS.

121 nd their contribution to the pathogenesis of HUS.

122 the understanding of the pathophysiology of HUS and could have an important effect on the developmen

123 apheresis (n = 13) during the acute phase of HUS had comparable outcomes.

124 e that, when performed during progression of HUS, passive immunization of mice with anti-Stx2 antibod

125 The higher rate of HUS was observed across all antibiotic classes used.

126 e farm prior to the first clinical report of HUS.

127 uraged because it might increase the risk of HUS development.

128 trongly associated with an increased risk of HUS, and eae was strongly associated with an increased r

129 Sera of HUS patients, but not healthy individuals, recognized Hc

130 and intestinal inflammation but no signs of HUS.

131 fice, moribund animals demonstrated signs of HUS: increased blood urea nitrogen and serum creatinine

132 accharide (LPS) caused signs and symptoms of HUS in mice, but the mechanism leading to renal failure

133 This type of HUS is characterized by obstruction of the glomeruli and

134 per limit of normal for age) and oligoanuric HUS.

135 sociated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal repla

136 sociated with the development of oligoanuric HUS.

137 104:H4 was equivalent to previous reports on HUS due to other types of Shiga toxin-producing E. coli

138 (HUS), thrombotic microangiopathy (TMA), or HUS-like events, exceeding the MTCD.

139 During 2000-2007, 627 pediatric HUS cases were reported.

140 ho had been included in the German Pediatric HUS Registry during the 2011 outbreak.

141 s population-based surveillance of pediatric HUS to measure the incidence of disease and to validate

142 nce rate for all reported cases of pediatric HUS was 0.78 per 100,000 children <18 years.

143 The overall incidence of pediatric HUS was affected by key characteristics of the surveilla

144 We report the incidence of pediatric HUS, which is defined as HUS in children <18 years.

145 re significantly different in HUS vs the pre-HUS phase of illness or uncomplicated infection.

146 Angiopoietin dysregulation preceded HUS and worsened as HUS developed.

147 The best way to prevent HUS is to prevent primary infection with Shiga-toxin-pro

148 erstanding of bacterial factors that promote HUS is incomplete.

149 Both patients had a history of recurrent HUS after transplantation.

150 s are hampered by the inability to reproduce HUS with thrombotic microangiopathy, hemolytic anemia, a

151 Herein are reviewed HUS and TTP along with recent progress shedding new ligh

152 athogenesis of STEC-HUS, aHUS, and secondary HUS are discussed.

153 ic features in STEC-HUS, aHUS, and secondary HUS are simultaneous damage to endothelial cells, intrav

154 olled complement activation, or as secondary HUS with a coexisting disease.

155 Some have secondary HUS with a coexisting disease or trigger such as autoimm

156 and some patients with STEC-HUS or secondary HUS.

157 xin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and A

158 cting data for the use of eculizumab in STEC HUS.

159 associated haemolytic uraemic syndrome (STEC HUS) is also provided.

160 isits in patients are recommended after STEC-HUS.

161 the hemolytic process occurring during STEC-HUS.

162 ent and future choices of therapies for STEC-HUS.

163 is evident in Shiga toxin-induced HUS (STEC-HUS).

164 Typical HUS (ie, STEC-HUS) follows a gastrointestinal infection with STEC, whe

165 The common pathogenetic features in STEC-HUS, aHUS, and secondary HUS are simultaneous damage to

166 and similarities in the pathogenesis of STEC-HUS, aHUS, and secondary HUS are discussed.

167 erived microvesicles from patients with STEC-HUS (n = 25) were investigated for the presence of C3 an

168 psilon mutation, and some patients with STEC-HUS or secondary HUS.

169 identified in 1 patient each with fatal Stx-HUS, the HELLP (hemolysis, elevated liver enzymes, and l

170 ogy of renal microvascular thrombosis in Stx-HUS is still ill-defined.

171 ding to podocyte dysfunction and loss in Stx-HUS.

172 nction may adversely affect evolution of Stx-HUS.

173 for using soluble TM in the treatment of Stx-HUS.

174 associated with a higher rate of subsequent HUS and should be avoided.

175 hoea-associated haemolytic uraemic syndrome (HUS) are caused by Shiga-toxin-producing bacteria; the p

176 ng 855 cases with hemolytic uremic syndrome (HUS) and 53 deaths.

177 or development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI).

178 e major causes of hemolytic uremic syndrome (HUS) and acute renal failure in children.

179 ngiopathy are the hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), the

180 similarities with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP).

181 purpura (TTP) and hemolytic uremic syndrome (HUS) are appropriately at the top of a clinician's diffe

182 ura (TTP) and the hemolytic uremic syndrome (HUS) are both characterized by thrombocytopenia, microan

183 hagic colitis and hemolytic uremic syndrome (HUS) by colonizing the gut mucosa and producing Shiga to

184 are isolated from hemolytic-uremic syndrome (HUS) cases more frequently than are strains that produce

185 Hemolytic uremic syndrome (HUS) caused by intestinal Shiga toxin-producing Escheric

186 Hemolytic-uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli in

187 Hemolytic-uremic syndrome (HUS) features episodes of small-vessel thrombosis result

188 STEC) can lead to hemolytic-uremic syndrome (HUS) in 5 to 10% of patients.

189 he development of hemolytic-uremic syndrome (HUS) in a small percentage of infected humans.

190 life-threatening hemolytic uremic syndrome (HUS) in any of 6 closed cohorts from 4 countries (1 coho

191 ith >800 cases of hemolytic uremic syndrome (HUS) in Germany, including 90 children.

192 Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition.

193 Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by in

194 Hemolytic-uremic syndrome (HUS) is a thrombotic microangiopathy that is characteriz

195 The hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, th

196 157:H7-associated hemolytic-uremic syndrome (HUS) is characterized by profound prothrombotic abnormal

197 Hemolytic uremic syndrome (HUS) is the life-threatenig sequela of intestinal infect

198 Postdiarrheal hemolytic uremic syndrome (HUS) is the most common cause of acute kidney failure am

199 The hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in

200 arrhea-associated hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in

201 Brain injury in hemolytic-uremic syndrome (HUS) may be enhanced by inflammatory cytokine up-regulat

202 Hemolytic uremic syndrome (HUS) occurred in 12 patients (10 infected with STEC O157

203 high incidence of hemolytic uremic syndrome (HUS) occurred in Germany in May 2011.

204 known outbreak of hemolytic uremic syndrome (HUS) occurred in northern Germany.

205 , 8 patients with hemolytic uremic syndrome (HUS) or bloody diarrhea were reported in France.

206 nfection leads to hemolytic uremic syndrome (HUS) or other complications.

207 Hemolytic-uremic syndrome (HUS) results from infection by Shiga toxin (Stx)-produci

208 ls with diarrheal hemolytic uremic syndrome (HUS) seen at our institution during the study period, 16

209 arrhea-associated hemolytic uremic syndrome (HUS), a disorder of glomerular ischemic damage and wides

210 arrhea-associated hemolytic uremic syndrome (HUS), a disorder of thrombocytopenia, microangiopathic h

211 s and can lead to hemolytic-uremic syndrome (HUS), a life-threatening condition that principally affe

212 agent that causes hemolytic uremic syndrome (HUS), a microangiopathic disease characterized by hemoly

213 ction can lead to hemolytic-uremic syndrome (HUS), a severe disease characterized by hemolysis and re

214 t can progress to hemolytic uremic syndrome (HUS), a systematic microvascular syndrome with predomina

215 ns that can cause hemolytic-uremic syndrome (HUS), a thrombotic microangiopathy, following infections

216 t and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals.

217 sible for causing hemolytic-uremic syndrome (HUS), and systemic administration of Shiga toxin (Stx)-s

218 Hemolytic-uremic syndrome (HUS), caused by Shiga toxin (Stx)-producing Escherichia

219 colitis (HC) and hemolytic uremic syndrome (HUS), due to the expression of one or more Shiga toxins

220 ations, including hemolytic-uremic syndrome (HUS), in animal models of disease.

221 e associated with hemolytic uremic syndrome (HUS), membranoproliferative glomerulonephritis (dense de

222 postenteropathic hemolytic uremic syndrome (HUS), most commonly caused by Shiga toxin (Stx)-producin

223 otentially lethal hemolytic uremic syndrome (HUS), particularly in children.

224 disease (SCD) and hemolytic uremic syndrome (HUS), pathological biophysical interactions among blood

225 rom patients with hemolytic-uremic syndrome (HUS), patients with less severe diarrheal disease, asymp

226 Hemolytic-uremic syndrome (HUS), the life-threatening complication following infect

227 0 doses developed hemolytic uremic syndrome (HUS), thrombotic microangiopathy (TMA), or HUS-like even

228 Hemolytic uremic syndrome (HUS), which is caused by Shiga toxin-producing Escherich

229 colitis (HC) and hemolytic-uremic syndrome (HUS), which is the most common cause of acute renal fail

230 nfection, such as hemolytic-uremic syndrome (HUS), zinc might be capable of preventing severe sequela

231 including 4 with hemolytic uremic syndrome (HUS).

232 viduals developed hemolytic-uremic syndrome (HUS).

233 ease consequence, hemolytic-uremic syndrome (HUS).

234 uses diarrhea and hemolytic uremic syndrome (HUS).

235 life-threatening hemolytic uremic syndrome (HUS).

236 colitis (HC) and hemolytic uremic syndrome (HUS).

237 leading cause of hemolytic uremic syndrome (HUS).

238 of children with hemolytic uremic syndrome (HUS).

239 purpura (TTP) and hemolytic uremic syndrome (HUS).

240 leading cause of hemolytic-uremic syndrome (HUS).

241 n associated with hemolytic-uremic syndrome (HUS).

242 t common cause of hemolytic-uremic syndrome (HUS).

243 spose to atypical hemolytic uremic syndrome (HUS).

244 oody diarrhea and hemolytic-uremic syndrome (HUS).

245 arrhea-associated hemolytic uremic syndrome (HUS).

246 colitis, and the hemolytic uremic syndrome (HUS).

247 th development of hemolytic uremic syndrome (HUS).

248 isted adults with hemolytic uremic syndrome (HUS).

249 coli (STEC) cause hemolytic uremic syndrome (HUS).

250 equela called the hemolytic uremic syndrome (HUS).

251 c colitis and the hemolytic-uremic syndrome (HUS).

252 Of the HUS cases in which STEC was isolated, 28 (90%) were attr

253 n the dialysis-maintained cohorts within the HUS (HR, 0.56; 95% CI, 0.35-0.91), HTN (HR, 0.50; 95% CI

254 = 11) exceeded the MTCD because of 2 HUS/TMA/HUS-like events.

255 mined, suggesting that several approaches to HUS surveillance can be used to track trends.

256 he inflammatory response that contributes to HUS development.

257 The vascular injury leading to HUS is likely to be well under way by the time infected

258 sis and direct endothelial injury leading to HUS phenotype.

259 re elevated in individuals who progressed to HUS.

260 of antibiotic administration in relation to HUS.

261 a significant proportion of non-shiga toxin HUS.

262 utive patients with clinically diagnosed TTP-HUS with assignment to 1 of 4 categories: less than 5% (

263 comes of the 16 patients with idiopathic TTP-HUS who had severe ADAMTS13 deficiency were variable and

264 The Oklahoma TTP-HUS (hemolytic uremic syndrome) Registry enrolled 70 con

265 <10%) in women enrolled in the Oklahoma TTP-HUS Registry from 1995 to 2012.

266 penic purpura-hemolytic uremic syndrome (TTP-HUS) is difficult because of lack of specific diagnostic

267 who may be appropriately diagnosed with TTP-HUS and who may respond to plasma exchange treatment.

268 We present a second case of TTP/HUS developing in an SPK recipient who was also receivin

269 croangiopathy (TMA); therefore, the term TTP/HUS should be avoided because it obscures the known or p

270 Typical HUS (ie, STEC-HUS) follows a gastrointestinal infection

271 iopoietins 1 and 2 (Ang-1/2), could underlie HUS pathophysiology.

272 risk-of-bias studies employing commonly used HUS criteria.

273 ransplantation probability in the waitlisted HUS cohort was 60% versus 42% to 49% (P < 0.001) in the

274 The primary and secondary outcomes were HUS (hematocrit <30% with smear evidence of hemolysis, p

275 efit over dialysis in waitlisted adults with HUS.

276 tx2a only were significantly associated with HUS (odds ratio, 14.2; 95% confidence interval, 7.9-25.6

277 iotic use were independently associated with HUS and, additionally, these variables were each associa

278 strains are more frequently associated with HUS than Stx1-producing strains.

279 of Stx2a, the major Stx type associated with HUS, on human renal glomerular endothelial cells (HRGEC)

280 ophage to the kidney disease associated with HUS.

281 ntribute to the renal damage associated with HUS.

282 promote the renal thrombosis associated with HUS.

283 Two cases with HUS died.

284 ation and adverse outcomes for children with HUS.

285 s (GN) were analyzed, and then compared with HUS patients.

286 ted by the bacteria, is directly linked with HUS.

287 ed by the bacterium, is directly linked with HUS.

288 TM(LeD/LeD) mice with HUS had a higher mortality rate than TM(wt/wt) mice.

289 associated with bloody diarrhea but not with HUS.

290 aa gene and STEC isolated from patients with HUS (6 of 46 strains) or diarrhea (2 of 29 strains) and

291 be an effective treatment for patients with HUS and/or individuals at high risk of developing HUS du

292 with STEC infection, including patients with HUS as well as STEC-infected outpatients without manifes

293 Patients with HUS receive only supportive treatment as the benefit of

294 Among the 30% to 50% of patients with HUS who have no detectable complement defect, some have

295 IF mutations in a panel of 76 patients with HUS.

296 ed in vitro and as observed in patients with HUS.

297 ure of hydration status at presentation with HUS was associated with the development of oligoanuric H

298 Two hundred nine patients presented with HUS.

299 Patients presenting with HUS had a significantly shortened shedding duration (med

300 has the strongest association worldwide with HUS.