A spatio-temporal reference model of the aging brain.

Both normal aging and neurodegenerative disorders such as Alzheimer's disease (AD) cause morphological changes of the brain. It is generally difficult to distinguish these two causes of morphological change by visual inspection of magnetic resonance (MR) images. To facilitate making this distinction and thus aid the diagnosis of neurodegenerative disorders, we propose a method for developing a spatio-temporal model of morphological differences in the brain due to normal aging. The method utilizes groupwise image registration to characterize morphological variation across brain scans of people with different ages. To extract the deformations that are due to normal aging we use partial least squares regression, which yields modes of deformations highly correlated with age, and corresponding scores for each input subject. Subsequently, we determine a distribution of morphologies as a function of age by fitting smooth percentile curves to these scores. This distribution is used as a reference to which a person's morphology score can be compared. We validate our method on two different datasets, using images from both cognitively normal subjects and patients with Alzheimer disease (AD). Results show that the proposed framework extracts the expected atrophy patterns. Moreover, the morphology scores of cognitively normal subjects are on average lower than the scores of AD subjects, indicating that morphology differences between AD subjects and healthy subjects can be partly explained by accelerated aging. With our methods we are able to assess accelerated brain aging on both population and individual level. A spatio-temporal aging brain model derived from 988 T1-weighted MR brain scans from a large population imaging study (age range 45.9-91.7y, mean age 68.3y) is made publicly available at www.agingbrain.nl.

[A man with polyarthralgia]. / Een man met polyartralgie.

A 46-year old Ghanaian man presented with immobilizing arthralgias in all joints except the forefoot, with a periarticular swelling most pronounced around the wrists and ankles. He had erythema nodosum and hilar lymphadenopathy on chest radiograph. We diagnosed Löfgren syndrome. The polyarthralgia recovered quickly with prednisone treatment.

Differences Between MR Brain Region Segmentation Methods: Impact on Single-Subject Analysis.

For the segmentation of magnetic resonance brain images into anatomical regions, numerous fully automated methods have been proposed and compared to reference segmentations obtained manually. However, systematic differences might exist between the resulting segmentations, depending on the segmentation method and underlying brain atlas. This potentially results in sensitivity differences to disease and can further complicate the comparison of individual patients to normative data. In this study, we aim to answer two research questions: 1) to what extent are methods interchangeable, as long as the same method is being used for computing normative volume distributions and patient-specific volumes? and 2) can different methods be used for computing normative volume distributions and assessing patient-specific volumes? To answer these questions, we compared volumes of six brain regions calculated by five state-of-the-art segmentation methods: Erasmus MC (EMC), FreeSurfer (FS), geodesic information flows (GIF), multi-atlas label propagation with expectation-maximization (MALP-EM), and model-based brain segmentation (MBS). We applied the methods on 988 non-demented (ND) subjects and computed the correlation (PCC-v) and absolute agreement (ICC-v) on the volumes. For most regions, the PCC-v was good ( > 0.75 ), indicating that volume differences between methods in ND subjects are mainly due to systematic differences. The ICC-v was generally lower, especially for the smaller regions, indicating that it is essential that the same method is used to generate normative and patient data. To evaluate the impact on single-subject analysis, we also applied the methods to 42 patients with Alzheimer's disease (AD). In the case where the normative distributions and the patient-specific volumes were calculated by the same method, the patient's distance to the normative distribution was assessed with the z-score. We determined the diagnostic value of this z-score, which showed to be consistent across methods. The absolute agreement on the AD patients' z-scores was high for regions of thalamus and putamen. This is encouraging as it indicates that the studied methods are interchangeable for these regions. For regions such as the hippocampus, amygdala, caudate nucleus and accumbens, and globus pallidus, not all method combinations showed a high ICC-z. Whether two methods are indeed interchangeable should be confirmed for the specific application and dataset of interest.

PCA-based groupwise image registration for quantitative MRI.

Quantitative magnetic resonance imaging (qMRI) is a technique for estimating quantitative tissue properties, such as the T1 and T2 relaxation times, apparent diffusion coefficient (ADC), and various perfusion measures. This estimation is achieved by acquiring multiple images with different acquisition parameters (or at multiple time points after injection of a contrast agent) and by fitting a qMRI signal model to the image intensities. Image registration is often necessary to compensate for misalignments due to subject motion and/or geometric distortions caused by the acquisition. However, large differences in image appearance make accurate image registration challenging. In this work, we propose a groupwise image registration method for compensating misalignment in qMRI. The groupwise formulation of the method eliminates the requirement of choosing a reference image, thus avoiding a registration bias. The method minimizes a cost function that is based on principal component analysis (PCA), exploiting the fact that intensity changes in qMRI can be described by a low-dimensional signal model, but not requiring knowledge on the specific acquisition model. The method was evaluated on 4D CT data of the lungs, and both real and synthetic images of five different qMRI applications: T1 mapping in a porcine heart, combined T1 and T2 mapping in carotid arteries, ADC mapping in the abdomen, diffusion tensor mapping in the brain, and dynamic contrast-enhanced mapping in the abdomen. Each application is based on a different acquisition model. The method is compared to a mutual information-based pairwise registration method and four other state-of-the-art groupwise registration methods. Registration accuracy is evaluated in terms of the precision of the estimated qMRI parameters, overlap of segmented structures, distance between corresponding landmarks, and smoothness of the deformation. In all qMRI applications the proposed method performed better than or equally well as competing methods, while avoiding the need to choose a reference image. It is also shown that the results of the conventional pairwise approach do depend on the choice of this reference image. We therefore conclude that our groupwise registration method with a similarity measure based on PCA is the preferred technique for compensating misalignments in qMRI.

Prophylactic parenteral cefuroxime: subcutaneous concentrations in laparotomy wounds.

Plasma and subcutaneous adipose tissue cefuroxime concentrations were measured in laparotomy wounds, by means of high-pressure liquid chromatography, in 12 patients undergoing elective abdominal operations. After intravenous administration of 1.5 g cefuroxime at induction of anaesthesia, the measured concentrations in serum and wound tissue during a 2 h period were above the MIC 90 of most micro-organisms derived from the alimentary tract. Tissue peak levels were reached within 15 min and the tissue half life was 1.5 h.

Selective management of abdominal and thoracic stab wounds with established peritoneal penetration: the eviscerated omentum.

In a prospective study involving 276 patients, stab wounds to the abdomen and lower chest with certain penetration into the peritoneal cavity were managed selectively. On the basis of physical findings, patients underwent either immediate laparotomy or close observation with frequent reexaminations and operation only if signs changed. The reliability of physical examination and the safety of nonoperative treatment in the absence of peritoneal signs were assessed. The overall incidence of major damage, including damage to the diaphragm, was 59.1 percent. Significant intraperitoneal visceral injury was found in 45.7 percent of patients with transabdominal stab wounds and in 25 percent of those with transthoracic stab wounds. Physical examination correctly predicted the findings in 90 to 96 percent of patients at initial assessment, with a sensitivity of 88.4 percent and a specificity of 93.9 percent. As delayed laparotomy after a change in signs during observation did not increase morbidity or hospital stay, and the unnecessary laparotomy rate in this study was 5.9 percent, we recommend a policy of selective management of abdominal and thoracic stab wounds with omental evisceration or other evidence of peritoneal penetration. Local wound care with amputation of the protruded omentum followed by close observation and monitoring of vital signs is safe surgical practice when no peritoneal signs or other indication for urgent exploration are present on admission.

Pitfalls in the management of penetrating chest trauma.

A prospective study designed specifically to analyze errors in management and iatrogenic complications was conducted on 234 consecutive patients with penetrating chest trauma. Eleven percent of penetrating pleural injuries were incorrectly diagnosed on initial physical and radiologic examination, but this led to wrong management decisions in only 4 percent. Decisions regarding intercostal tube drainage were particularly inaccurate when emergency intubation was required prior to chest radiography. Atypical clinical features of penetrating cardiac injuries caused delay in diagnosis and thoracotomy in 3 of 14 patients. Only two of four mediastinal vascular injuries were recognized on initial examination. Transdiaphragmatic injuries were initially missed in 5 of 14 patients. This resulted in management errors and delay in these patients. Awareness of atypical presentations and circumstances in which misjudgments and wrong decisions are prone to occur should help to avoid pitfalls and reduce mortality from penetrating chest trauma.

The value of adjuvant systemic antibiotic therapy in localised wound infections among hospital patients: a comparative study.

In a prospective randomised double-blind controlled trial that involved 73 patients with non-invasive wound infections receiving local wound treatment, the effect of adjuvant systemic antibiotic therapy was compared with that of a placebo. On inspection, more wounds were assessed as clinically clean after administration of an antibiotic than after the placebo was given although this difference was not statistically significant. Microbiological evaluation, however, showed a significantly higher cure of sepsis and elimination of individual organisms (P less than 0.05) after antibiotic therapy. Furthermore, eradication of antibiotic-susceptible organisms was significantly greater than that of resistant organisms (P less than 0.005), indicating adequate penetration of antibiotic into the septic wound exudate. The results suggest that appropriate adjuvant systemic antibiotic therapy in the management of infected wounds promotes bacterial clearance and this may enhance healing of wounds.

Resting metabolic rate of esophageal carcinoma patients: a model for energy expenditure measurement in a homogenous cancer population.

In cancer patients controversy exists as to the nature of changes in resting metabolic rate (RMR) and their contribution to cachexia. This study describes the fasting indirect calorimetry, and nutritional measurements made on a homogeneous group of Black patients with carcinoma of the esophagus. It compares them with a reference group. All cancer patients had localized disease and were markedly malnourished. They were on average 20 to 25% lighter than reference subjects. In the cancer patients, the triceps skinfold thickness (TSF) in mm and the hand grip strength in kg/m2, mean and SD, were, respectively, 7.3 +/- 2.8 and 28 +/- 6 for men and 12 +/- 5 and 22 +/- 3.5 for women, and were significantly lower than those of the reference subjects. Fat-free mass was calculated from the TSF measurements. In men with cancer RMR (6.06 MJ/day +/- 0.56) was significantly lower than the reference subjects values (7.07 MJ/day +/- 0.64) p = 0.002. In women with cancer RMR was on average 2 MJ/day less than in controls but this difference failed to reach significance. However, when expressed per kg fat free mass, or per kg body weight this difference is no longer apparent the RMR being 0.14 MJ/kg/fat free mass in both groups. Our interpretation is that there is no direct effect of the tumour on RMR and that energy expenditure changes are secondary to body composition changes.

Chronic pancreatitis with biliary obstruction.

In a 4-year review of 509 patients with chronic pancreatitis, the incidence of clinically manifest fixed common bile duct (CBD) stenosis was 9% (45 patients). In 76% this was alcohol related, and pancreatic calcification was present in 51%. All patients presented with unrelenting jaundice and five (11%) had cholangitis. The mean serum bilirubin (165 +/- 108, normal 0-17 mumol/l), alkaline phosphatase (1790 +/- 1143, normal 73-207 U/l) and gamma glutamyl transferase (798 +/- 660, normal 7-64 U/l) were markedly raised. Diabetes occurred in 8 (18%). A biliary drainage operation was performed in 43 patients and 11 had concomitant pancreaticojejunostomy. Endoscopic retrograde cholangiopancreatography (ECRP) provided valuable information preoperatively in outlining both biliary and pancreatic disease in selecting patients for dual ductal drainage. Minor complications not related to biliary anastomosis occurred in 14%. Four patients died (9%), two from pseudocyst-related haemorrhage. Jaundice was successfully relieved in all and did not recur during follow-up. No secondary biliary cirrhosis was encountered, but varying degrees of portal fibrosis were present in 75% of liver biopsies. The commonest biliary pathogen was E. coli. It is recommended that a biliary bypass operation be performed when the diagnosis is radiologically confirmed and no improvement occurs within 1 month.

Surgical intervention for regional complications of chronic pancreatitis.

In a five year review of 648 patients with chronic pancreatitis, 446 (68.8%) were documented with regional complications consisting of biliary, duodenal or colonic obstruction, pseudocysts, haemorrhage, pancreatic ascites and gastric varices. Although the majority could be treated conservatively, surgical intervention was needed in 129 patients (28.9%). The commonest operations were choledocho-duodenostomy for distal bile duct obstruction, gastro-enterostomy for duodenal obstruction, local resection for colon obstruction, cyst-gastrostomy for pseudocysts, duct-enteric anastomosis for pancreatic ascites and splenectomy for gastric varices. Operative mortality was 8.5% and morbidity 27.9%. During 1-5 year follow-up, re-admission for pancreatitis was needed in 24%. No secondary biliary cirrhosis was encountered in long standing bile duct obstruction, but fibrosis was present in 73% of liver biopsies. Cholangitis occurred in 14%. Angiographic embolisation was useful in the control of massive bleeding from peri-pancreatic visceral arteries. Although relief of pain in chronic pancreatitis has generally been disappointing, regional complications, occurring in the majority of patients, can be corrected satisfactorily by surgical intervention.

The influence of splenectomy on infective morbidity after colonic and splenic injuries.

OBJECTIVE: To establish the incidence of early postoperative infections after civilian injuries to the spleen, colon, or both and assess the effect of splenectomy on outcome. DESIGN: Retrospective study of case notes. SETTING: University hospital. SUBJECTS: 403 Patients of whom 353 had splenic injuries, 91 with associated colonic injuries, together with 50 randomly selected patients with colonic injuries alone. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: 45 Patients had splenectomy and colonic injury (group 1), 46 had a colonic injury and the spleen conserved (group 2) 50 had colonic injury alone (group 3), 143 had splenectomy for injured spleen without colonic injury (group 4), and 119 had the spleen injured and conserved without colonic injury (group 5). Their mean age was 28 years. Overall mean Injury Severity Score (ISS) was 30.1, and Abdominal Trauma Index (ATI) 22.4. 68/403 died (17%), more than half within 48 hours. Early mortality was higher in both groups in which the spleen was removed but after stratification by ISS and ATI the differences were not significant. Late mortality (after 48 hours) associated with sepsis did not differ significantly among the groups, nor did the rate of infective complications. Mechanism and severity of injury had the most influence on morbidity and mortality. CONCLUSION: Removal of an injured spleen does not have an adverse influence on the incidence of serious infective complications in the early postoperative period in patients with injuries to the spleen, the colon, or both.

Treatment of persistent and complicated pancreatic pseudocysts.

In a review of 1895 patients admitted with pancreatitis during a 4-year period, 241 (12.7%) were identified as having pseudocysts. The majority of these were treated without operation, but 59 patients (24.5%) needed surgical intervention because of persistence (17 cases) or development of complications (biliary obstruction in 16, infection in 12, duodenal obstruction in ten and haemorrhage in four). Most cysts (68%) resulted from alcohol-related chronic pancreatitis. Blunt abdominal trauma was the cause in three. Operations included internal drainage in 35 (cystogastrostomy in 23, cystojejunostomy with Roux-en-Y in ten and cystoduodenostomy in two), external drainage in 20, pancreatic resection in two, and gastroenteric or bilioenteric bypass in ten. There were six postoperative deaths (10.2%), one after internal drainage (3%) and 5 (25%) after external drainage (P < 0.01, Fisher's exact test). Pseudocyst decompression failed to relieve biliary obstruction in half of the patients and biliary-enteric anastomosis was necessary because of a stricture in the distal bile duct. Massive bleeding from pseudocyst-related false aneurysms was successfully controlled by transcatheter angiographic embolization in four patients. During 1-5 years' follow-up, 24 of the 53 surviving patients (45%) were readmitted with pancreatitis and three of these died. Pseudocysts recurred in three patients, with spontaneous resolution in two and need for operation in one. It is concluded that operative treatment of complicated pseudocysts carries a substantial mortality rate. The need for additional biliary-enteric bypass after cyst decompression should be carefully assessed during operation. Angiographic embolization of pseudocyst haemorrhage is a valuable therapeutic manoeuvre.

Prospective study of the yield of physical examination compared with chest radiography in penetrating thoracic trauma.

A prospective study was conducted on 102 patients (84 male), with a median age of 27 years, who had sustained a penetrating chest wound to evaluate the ability of physical examination in comparison with chest radiography to determine management of these injuries. Knife wounds accounted for 92% of the injuries. Fifty three patients had a small collection of air or fluid in their pleural cavity that was not drained. Fifty six hemithoraces had a large collection of fluid or air and were treated by tube thoracostomy. Physical examination at presentation detected large collections of air and fluid correctly and predicted appropriate management (sensitivity 96%, specificity 94%). Residual collections of air or fluid or both were also predicted correctly by clinical examination. Seven small collections increased in size and required intubation. Routine pre-extubation radiographs were found to be of little value in management and their routine use is not recommended. Four patients required late thoracotomy for decortication. By using a policy of selective intubation, frequent clinical reassessment, and chest radiography when relevant, experienced trauma surgeons can manage most penetrating pleural injuries with an acceptably low complication rate.

Esophageal transection versus injection sclerotherapy in the management of bleeding esophageal varices in patients at high risk.

In a prospective randomized trial of 76 patients at high risk with bleeding esophageal varices, transection of the esophagus with the EEA stapling apparatus was compared with injection sclerotherapy in the management of patients with Child's class B and C liver status. Thirty-nine patients underwent transection and 37 patients, sclerotherapy with a total of 92 injection procedures (2.4 per patient). The perioperative mortality (less than 30 days) was 28.9 per cent overall; 33.3 per cent for esophageal transection and 24.3 per cent for injection sclerotherapy (chi 2 = 0.375, p greater than 0.05). Gross ascites, severe encephalopathy and emergency operations were associated with a high mortality in the transection group, but other risk factors such as age and hypersplenism did not influence the outcome in either group. Only patients in Child's class C died after transection, but patients who died in the sclerotherapy group (mainly from recurrent bleeding) included patients from both Child's class B and C. Early recurrence of nonfatal bleeding affected one of 39 patients (2.5 per cent) after transection but was evident in 18 of 37 patients (48.6 per cent) after sclerotherapy (chi 2 = 19.12, p greater than 0.0005) and six patients died. Hemorrhage did not recur after transection during a follow-up period of two years, but a further 22 episodes of bleeding were recorded in 13 patients receiving sclerotherapy with five deaths. Postoperative complications and long term morbidity were similar in the two groups. Including readmissions for bleeding and repeat procedures, the mean hospital stay per patient was shorter for transection (14.5 versus 19.1 days) and the requirements for blood were less (1.9 units per patient versus 3.6 units per patient) than for sclerotherapy. It is concluded that esophageal transection effectively protects against short term recurrence of bleeding. Preoperative control of gross ascites will further reduce the mortality and comatose patients should be excluded from operation. Sclerotherapy provides little if any protection against recurrent bleeding and its use in the management of variceal hemorrhage in patients with advanced liver disease remains questionable. It is recommended as a temporary measure in patients at high risk until such time that more effective surgical treatment can be performed.

Prevention of wound sepsis in amputations by peri-operative antibiotic cover with an amoxycillin-clavulanic acid combination.

In a series of 44 patients with lower limb ischaemia requiring amputation for major limb sepsis, the performance of a new antibiotic combination with beta-lactamase-inhibiting properties, amoxycillin plus clavulanic acid (A-CA) (Augmentin; Beecham), was compared with that of penicillin in the prevention of wound infection. The sepsis rate of 12,9% in the group of patients receiving peri-operative A-CA was significantly lower than the 76,9% in the penicillin control group (x2 = 14,48; P less than 0,001). It is concluded that there is a need for peri-operative antibiotic cover in this situation and that A-CA appears to be highly effective. No statistical difference was found as regards development of sepsis in wounds closed primarily or left open while under A-CA cover.

Management of splenic trauma: the Durban experience.

In a retrospective survey of splenic trauma managed at a teaching hospital, the data of 127 patients during a 2 year period have been analysed. Splenic conservation was achieved in 47 laparotomies (38.8 per cent). Six patients with blunt abdominal trauma (4.7 per cent of all patients) were managed non-operatively. Splenic conservation by suture with or without packing with omentum or oxidized cellulose was successful in 27 out of 37 attempts. Failure of this technique was easily recognized during laparotomy and no patient required re-operation for continued splenic bleeding after splenorrhaphy. There was no significant difference between successful conservation of the spleen at laparotomy of patients below the median age (28 years) and older patients. Wound sepsis was increased after splenectomy (P less than 0.05). Splenic conservation is not appropriate for all types of splenic injury. Where conservation is not possible splenectomy and re-implantation is recommended.