Assessment of therapeutic response in ankylosing spondylitis patients undergoing anti-tumour necrosis factor therapy by whole-body magnetic resonance imaging.

OBJECTIVES: Multifocal musculoskeletal inflammation is common in ankylosing spondylitis (AS) and is effectively treated by expensive anti-TNF (tumour necrosis factor) therapy. This study evaluated assessment of response by whole-body (WB) MRI compared with clinical assessment in AS patients during etanercept therapy. METHODS: Ten patients with AS underwent a 12-month therapy with etanercept. Clinical markers were monitored [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C-reactive protein (CRP)] and patients underwent WBMRI (1.5 T, STIR and T1-weighted) at three different time points (0, 26 and 52 weeks). WBMRI was evaluated and correlated with clinical scores. RESULTS: The BASDAI index decreased under therapy from 5.5 ± 0.5 (week 0) to 1.7 ± 0.5 (week 52, P < 0.05). CRP declined from 15.7 ± 2.2 mg/dl (week 0) to 0.9 ± 0.9 mg/dl (week 52, P < 0.05). In WBMRI, the sum of all lesions showed a significant decrease from week 0 (38.9 ± 3.4) to week 52 (2.2 ± 0.9, 94.3 % reduction). WBMRI detected more areas of synovitis and enthesitis than clinical examination alone. CONCLUSIONS: AS activity significantly decreased under etanercept therapy, which was proven by clinical examination and WBMRI. WBMRI detected more inflammatory lesions than clinical examination alone. The results suggest that WBMRI improves the detection of inflammatory changes and the assessment of their course under therapy. KEY POINTS: • Multifocal musculoskeletal inflammation in AS is effectively treated by anti-TNF therapy. • Inflammatory lesions can be assessed by clinical examination and whole-body MRI. • AS activity significantly decreased under therapy as shown by WBMRI/clinical examination. • WBMRI detected more inflammatory lesions than clinical examination alone. • WBMRI improves detection of inflammatory changes and may help evaluation of therapy.

Radiation exposure and image quality of normal computed tomography brain images acquired with automated and organ-based tube current modulation multiband filtering and iterative reconstruction.

OBJECTIVES: We sought to determine whether radiation dose can be reduced and image quality improved in computed tomography (CT) images of the brain that were acquired with automated exposure control (AEC), organ-based tube current modulation (TCM), multiband filtration (MBF), and iterative reconstruction in image space (IRIS). METHODS: An Alderson-Rando-phantom, equipped with thermoluminescent dosimeters, was used to determine the radiation exposure of organs within the head and neck by different CT brain scan modes. We measured the noise and signal-to-noise ratios and subjectively graded quality criteria in different territories of the brain in spiral CT images of 150 patients. We also derived the radiation exposure from the patient protocols. RESULTS: In the phantom, AEC and TCM reduced the radiation exposure of the lenses, cerebrum, cerebellum, and thyroid gland by 41.9%, 34.5%, 30.5%, and 34.9%, respectively. Brain CT scans from patients investigated with AEC, TCM, MBF, and IRIS were found to have significantly better image quality than with conventional filtered back projection. In addition, the CT dose index and dose-length product were significantly lower with AEC, TCM, MBF, and IRIS by 24.1% and 20.2%, respectively. CONCLUSION: The combination of AEC, TCM, MBF, and IRIS improves image quality while radiation exposure can be reduced, particularly in dose-sensitive organs, such as the lenses and thyroid gland.

Vagal innervation and early postoperative ileus in mice.

INTRODUCTION: Postoperative ileus is characterized by infiltrates of leukocytes in the gut wall 24 h after surgery, which is subject to vagal modulation. We hypothesized that vagal modulation is irrelevant during earlier hours of postoperative ileus and aimed to determine whether afferent neuronal feedback to the central nervous system is altered by vagal innervation during this early period. METHODS: C57BL6 mice were laparotomized and received standardized small bowel manipulation to induce postoperative ileus. Subgroups were vagotomized 3-4 days prior to experiments while control animals were sham-operated. Three or 9 h later a 2-cm jejunal segment was harvested for multi-unit mesenteric afferent nerve recordings in vitro. Intestinal motility was monitored continuously and intestinal muscularis was stained for myeloperoxidase to determine infiltration of leukocytes. RESULTS: Peak amplitudes of intestinal motility and afferent nerve discharge at baseline were not different in all subgroups. Afferent discharge to 5-HT (500 µM) was virtually absent following vagotomy at 3 and 9 h of postoperative ileus (POI) compared to controls (p < 0.05). Maximum afferent nerve discharge to bradykinin and peak firing during maximum distension at 60 mmHg was not different in all subgroups while luminal distension from 10 to 30 mmHg was lower at 3 h of POI following vagotomy compared to controls (p < 0.05). The number of myeloperoxidase positive cells was similar at 3 h of POI in both subgroups; however, at 9 h of POI, ileus counts were increased to 713 ± 99 cells following vagotomy compared to 47 ± 6 cells per square millimeter in control animals. CONCLUSIONS: Vagal afferents mediate sensitivity to low-threshold distension and 5-HT during postoperative ileus but not to high-threshold distension and bradykinin. Vagal inhibition of the intestinal immune response is present at 9 h but not detectable earlier, i.e., at 3 h of postoperative ileus when spinal reflex inhibition may prevail.

Co-morbidity and postsurgical outcome in patients with perforated sigmoid diverticulitis.

INTRODUCTION: It was previously reported that in patients with acute perforated diverticulitis with Hinchey categories I to III sigmoidectomy with primary anastomosis (PA) is superior to Hartmann's procedure (HP) as later closure of colostomy involves substantial morbidity. We evaluated our experience with PA for patients with perforated diverticulitis over a 10-year period and aimed to investigate whether Hinchey category or co-morbidity are more relevant for postoperative outcome. METHODS: Records of all patients treated at our institution for sigmoid diverticulitis between 1996 and 2006 were retrieved from an in-hospital database (N = 787, median age 66 years, range 30 to 94, female:male ratio 1.3:1); 73 patients who underwent immediate emergency surgery for perforated diverticulitis were included in this study. American Society of Anesthesiology (ASA) classification to gauge co-morbidity and Hinchey category for intraoperative extent of inflammation were evaluated as regards their relevance for postoperative mortality and major complications. RESULTS: 47 patients (64%) underwent sigmoid colectomy and PA, which was combined with loop ileostomy in 11 patients (15%). Sigmoid colectomy and HP was performed in 26 patients (36%). Major postoperative complications occurred in 26 patients (36%). In the PA group, 10 of 47 patients (21%) had anastomotic leakage. Three leakages occurred despite a loop ileostomy. Anastomotic leakage was independent of Hinchey category (Hinchey I: three patients, Hinchey II: four patients, Hinchey III: three patients, n.s.), but associated with co-morbidity (one patient ASA II, six patients ASA III, three patients ASA IV, P < 0.05). Total mortality was 12%. Seven patients died after HP and two patients after PA. No mortality was observed in PA patients with loop ileostomy. CONCLUSIONS: Emergency surgery for perforated sigmoid diverticulitis is associated with high morbidity and mortality rates. Anastomotic leakage was associated with patient co-morbidity rather than with intraoperative Hinchey category, suggesting that the decision to perform PA should better be based on patient's general condition rather than on intraoperative extent of inflammation.

Role of the vagus nerve on the development of postoperative ileus.

INTRODUCTION: Postoperative ileus involves reflex inhibition of intestinal motility within hours after surgery and a subsequent intestinal inflammatory response that is characterized by efferent vagal modulation via acetylcholine receptors on intestinal macrophages. We aimed to characterize the role of vagal modulation of intestinal motility during the early hours after surgery. METHODS: C57BL6 mice underwent laparotomy and standardized small bowel manipulation to induce postoperative ileus. Subgroups were vagotomized 3-4 days prior to experiments or received pharmacological inhibition of the acetylcholine alpha7 subunit with the inhibitor alpha-bungarotoxin, while control animals were sham operated and remained otherwise untreated. Three hours later, a 2-cm jejunal segment was harvested with the mesentery attached. Mesenteric afferent nerve recordings were established in an organ bath generating a multiunit signal with subsequent computerized analysis. Intraluminal pressure was continuously recorded to assess intestinal motility. Afferent nerve responses were quantified at baseline and to chemical stimulation with bradykinin (0.5 microM) or serotonin (5-HT; 500 microM) and following mechanical stimulation by continuous ramp distension to 60 mmHg. RESULTS: Peak amplitudes of intestinal motility and afferent nerve discharge at baseline were not different following chronic vagotomy, alpha-bungarotoxin or sham operation. Maximum afferent discharge to 5-HT following alpha-bungarotoxin was comparable to sham controls, while the response was reduced in chronically vagotomized animals (p < 0.05). Maximum afferent nerve discharge to bradykinin and peak firing during maximum distension at 60 mmHg was similar in the different subgroups. At luminal distension from 10 to 30 mmHg, afferent discharge was lower in vagotomized animals compared to sham controls (p < 0.05) but unchanged after alpha-bungarotoxin. CONCLUSIONS: Sensitivity to low-threshold distension and 5-HT is mediated via vagal afferents during postoperative ileus, while sensitivity to high-threshold distension and bradykinin is independent of vagal afferent innervation. Early inhibition of intestinal motility at 3 h after onset of postoperative ileus does not appear to depend on vagal innervation.