N 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 22948146 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 inhibitor 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 creatinine (.1.2 mg/dl) and/or reduced glomerular Autophagy 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 Epigenetic Reader Domain thickening of the colonic wall. doi:10.1371/journal.pone.0055278.gEHEC O104 Infection in Hospitalized PatientsFigure 2. Endoscopic image (a) of EHEC O104 induced hemorrhagic necrotizing colitis and corresponding histology (b). PAS staining of colon mucosa after surgical resection: massive granulocyte infiltrations with colonic crypts (C) and severe ulceration: disruption (asterix) of muscularis Autophagy mucosae (MM), fibrin deposits (arrows) and edema. doi:10.1371/journal.pone.0055278.gFigure 3. Photomicrographs of two separate gut sections from a patient with EHEC colitis. Panels (A) and (B) are stained with CD31 to enumerate endothelium lining the vessels (406 magnification). (C) and (D) are stained to show VCAM-1 expression in endothelium, indicating inflammatory activation (406 magnification). doi:10.1371/journal.pone.0055278.gEHEC O104 Infection in Hospitalized PatientsTable 2. Stool frequency and laboratory data at different courses of disease.Hospital-admission n = 61 Stool frequency [/d] Hb [g/dl] Thrombocytes [/nl] CRP [mg/l] Creatinine [mg/dl] LDH [U/l] 2163 13.760.3 218612 35.767.2 1.360.1Onset of HUS n = 36 862 12.N 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 22948146 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 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. Endoscopic image (a) of EHEC O104 induced hemorrhagic necrotizing colitis and corresponding histology (b). PAS staining of colon mucosa after surgical resection: massive granulocyte infiltrations with colonic crypts (C) and severe ulceration: disruption (asterix) of muscularis mucosae (MM), fibrin deposits (arrows) and edema. doi:10.1371/journal.pone.0055278.gFigure 3. Photomicrographs of two separate gut sections from a patient with EHEC colitis. Panels (A) and (B) are stained with CD31 to enumerate endothelium lining the vessels (406 magnification). (C) and (D) are stained to show VCAM-1 expression in endothelium, indicating inflammatory activation (406 magnification). doi:10.1371/journal.pone.0055278.gEHEC O104 Infection in Hospitalized PatientsTable 2. Stool frequency and laboratory data at different courses of disease.Hospital-admission n = 61 Stool frequency [/d] Hb [g/dl] Thrombocytes [/nl] CRP [mg/l] Creatinine [mg/dl] LDH [U/l] 2163 13.760.3 218612 35.767.2 1.360.1Onset of HUS n = 36 862 12.N 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 22948146 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 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. Endoscopic image (a) of EHEC O104 induced hemorrhagic necrotizing colitis and corresponding histology (b). PAS staining of colon mucosa after surgical resection: massive granulocyte infiltrations with colonic crypts (C) and severe ulceration: disruption (asterix) of muscularis mucosae (MM), fibrin deposits (arrows) and edema. doi:10.1371/journal.pone.0055278.gFigure 3. Photomicrographs of two separate gut sections from a patient with EHEC colitis. Panels (A) and (B) are stained with CD31 to enumerate endothelium lining the vessels (406 magnification). (C) and (D) are stained to show VCAM-1 expression in endothelium, indicating inflammatory activation (406 magnification). doi:10.1371/journal.pone.0055278.gEHEC O104 Infection in Hospitalized PatientsTable 2. Stool frequency and laboratory data at different courses of disease.Hospital-admission n = 61 Stool frequency [/d] Hb [g/dl] Thrombocytes [/nl] CRP [mg/l] Creatinine [mg/dl] LDH [U/l] 2163 13.760.3 218612 35.767.2 1.360.1Onset of HUS n = 36 862 12.N 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 22948146 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 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. Endoscopic image (a) of EHEC O104 induced hemorrhagic necrotizing colitis and corresponding histology (b). PAS staining of colon mucosa after surgical resection: massive granulocyte infiltrations with colonic crypts (C) and severe ulceration: disruption (asterix) of muscularis mucosae (MM), fibrin deposits (arrows) and edema. doi:10.1371/journal.pone.0055278.gFigure 3. Photomicrographs of two separate gut sections from a patient with EHEC colitis. Panels (A) and (B) are stained with CD31 to enumerate endothelium lining the vessels (406 magnification). (C) and (D) are stained to show VCAM-1 expression in endothelium, indicating inflammatory activation (406 magnification). doi:10.1371/journal.pone.0055278.gEHEC O104 Infection in Hospitalized PatientsTable 2. Stool frequency and laboratory data at different courses of disease.Hospital-admission n = 61 Stool frequency [/d] Hb [g/dl] Thrombocytes [/nl] CRP [mg/l] Creatinine [mg/dl] LDH [U/l] 2163 13.760.3 218612 35.767.2 1.360.1Onset of HUS n = 36 862 12.
