Severe (n = 4; 7 ) diarrhoea. Twelve HIV-RT inhibitor 1 patients (20 ) fulfilled the criteria of HUS at time of admission. The mean age of patients was 4462 years, 37 females and 24 males. The mean interval between onset ofClostridium difficile Norovirus Campylobacter jejuni Preexisting renal disease Preexisting hypertension doi:10.1371/journal.pone.0055278.tEHEC O104 223488-57-1 site infection in Hospitalized Patientstypical abdominal appearance on ultrasound was that of left sided colitis with marked thickening of bowel wall and ascites (Fig. 1). At the beginning of the outbreak three of the first patients underwent colonoscopy for differential diagnosis of bloody diarrhoea. In these cases, endoscopy showed a severe ulcerative colitis with spontaneous bleeding of the highly inflamed mucosa (Fig. 2a). Histologic examination demonstrated severe inflammation with dense infiltrations of lymphocytes and granulocytes, ulcerative disruption of the epithelial lining and fibrin deposits (Fig. 2b). Immunohistochemistry of blood vessels in areas of inflammation revealed an intact endothelial lining with induced endothelial cell expression of VCAM-1 indicative of inflammatory activation (Fig. 3).Further Course, Complications, and TherapySeventeen patients (28 ) with diarrhoea improved continuously and could be discharged free of symptoms after 761 days. The remaining 44 (72 ) patients developed complications. In many cases complications were preceded by a stagnation of bowel movements. The time-wise sequence of symptoms and complications is shown in Fig. 4. The longest interval between onset of diarrhoea and onset of complications was 14 days. The most frequent and severe complication was HUS which developed in 36 cases (59 ; male/female: 11/25). In 17 (47 ) out of 36 HUS-patients diarrhoea had already ceased at time of theonset of HUS. All patients with HUS suffered from typical haemolysis, progressive renal failure, and thrombocytopenia. The cumulative laboratory findings of HUS patients are shown in Fig. 5. The mean duration of HUS was 1261 days. 33/36 (92 ) patients with HUS were treated with plasma-separation (median: 10 cycles (3?0), median duration: 9 days (2?5)) and dialysis in cases of renal failure (16 patients; 44 ). While 17 (47 ) patients reached normal levels of the serum creatinine subsequent to HUS, 19 patients displayed prolonged kidney damage, indicated by sustained elevations of serum 15857111 creatinine (.1.2 mg/dl) and/or reduced glomerular filtration rate (GFR). Two patients had to continue dialysis at time of discharge. All HUS patients developed a severe capillary leak syndrome with a rapid onset along with first laboratory signs of HUS and had therefore to be treated with extensive replacement of fluids. Besides generalized oedema, most patients suffered from pleural effusions (29/36; 81 ) and ascites (28/36; 78 ). Neurologic complications (n = 26/61; 43 ) occurred 4 days (2?11) after the diagnosis of HUS. Patients presented with epileptic seizures (n = 13; 50 ), oculomotor dysfunction (n = 19; 73 ), neuropsychiatric syndromes (n = 18; 69 ), disorientation (n = 15; 57 ), somnolence (n = 11; 42 ), aphasia (n = 9; 34 ), tremor (n = 9; 34 ), cortical blindness (n = 3; 11 ), choreatic syndrome (n = 1; 4 ). In nearly all cases the initial neurological symptomsFigure 1. Typical ultrasound image in EHEC O104 infection. left sided colitis with marked thickening of the colonic wall. doi:10.1371/journal.pone.0055278.gEHEC O104 Infection in Hospitalized PatientsFigure 2. Endos.Severe (n = 4; 7 ) diarrhoea. Twelve patients (20 ) fulfilled the criteria of HUS at time of admission. The mean age of patients was 4462 years, 37 females and 24 males. The mean interval between onset ofClostridium difficile Norovirus Campylobacter jejuni Preexisting renal disease Preexisting hypertension doi:10.1371/journal.pone.0055278.tEHEC O104 Infection in Hospitalized Patientstypical abdominal appearance on ultrasound was that of left sided colitis with marked thickening of bowel wall and ascites (Fig. 1). At the beginning of the outbreak three of the first patients underwent colonoscopy for differential diagnosis of bloody diarrhoea. In these cases, endoscopy showed a severe ulcerative colitis with spontaneous bleeding of the highly inflamed mucosa (Fig. 2a). Histologic examination demonstrated severe inflammation with dense infiltrations of lymphocytes and granulocytes, ulcerative disruption of the epithelial lining and fibrin deposits (Fig. 2b). Immunohistochemistry of blood vessels in areas of inflammation revealed an intact endothelial lining with induced endothelial cell expression of VCAM-1 indicative of inflammatory activation (Fig. 3).Further Course, Complications, and TherapySeventeen patients (28 ) with diarrhoea improved continuously and could be discharged free of symptoms after 761 days. The remaining 44 (72 ) patients developed complications. In many cases complications were preceded by a stagnation of bowel movements. The time-wise sequence of symptoms and complications is shown in Fig. 4. The longest interval between onset of diarrhoea and onset of complications was 14 days. The most frequent and severe complication was HUS which developed in 36 cases (59 ; male/female: 11/25). In 17 (47 ) out of 36 HUS-patients diarrhoea had already ceased at time of theonset of HUS. All patients with HUS suffered from typical haemolysis, progressive renal failure, and thrombocytopenia. The cumulative laboratory findings of HUS patients are shown in Fig. 5. The mean duration of HUS was 1261 days. 33/36 (92 ) patients with HUS were treated with plasma-separation (median: 10 cycles (3?0), median duration: 9 days (2?5)) and dialysis in cases of renal failure (16 patients; 44 ). While 17 (47 ) patients reached normal levels of the serum creatinine subsequent to HUS, 19 patients displayed prolonged kidney damage, indicated by sustained elevations of serum 15857111 creatinine (.1.2 mg/dl) and/or reduced glomerular filtration rate (GFR). Two patients had to continue dialysis at time of discharge. All HUS patients developed a severe capillary leak syndrome with a rapid onset along with first laboratory signs of HUS and had therefore to be treated with extensive replacement of fluids. Besides generalized oedema, most patients suffered from pleural effusions (29/36; 81 ) and ascites (28/36; 78 ). Neurologic complications (n = 26/61; 43 ) occurred 4 days (2?11) after the diagnosis of HUS. Patients presented with epileptic seizures (n = 13; 50 ), oculomotor dysfunction (n = 19; 73 ), neuropsychiatric syndromes (n = 18; 69 ), disorientation (n = 15; 57 ), somnolence (n = 11; 42 ), aphasia (n = 9; 34 ), tremor (n = 9; 34 ), cortical blindness (n = 3; 11 ), choreatic syndrome (n = 1; 4 ). In nearly all cases the initial neurological symptomsFigure 1. Typical ultrasound image in EHEC O104 infection. left sided colitis with marked thickening of the colonic wall. doi:10.1371/journal.pone.0055278.gEHEC O104 Infection in Hospitalized PatientsFigure 2. Endos.
