Calprotectin as Diagnostic Marker for Hepatic Encephalopathy and Spontaneous Bacterial Peritonitis in Cirrhosis.

BACKGROUND: Calprotectin is a well-established marker for intestinal inflammation, mainly in inflammatory bowel disease, and represents one of the most studied biomarkers in stool samples. METHODS: Apart from its important diagnostic role in inflammatory bowel disease, there are few studies showing that calprotectin can also be used as a diagnostic tool in patients suffering from hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP) in cirrhosis. RESULTS: Since calprotectin concentration in the human stool or in ascites is elevated at an early stage of inflammation, it might serve as an early screening tool for patients suffering from cirrhosis who are at risk to develop these conditions. As detection and monitoring of HE and SBP may be unclear and resource-intensive, identification of valid new markers of disease activity is necessary. In this review, we summarize the current knowledge of calprotectin as a diagnostic biomarker in cirrhosis, indicating that it is a highly promising diagnostic surrogate marker to screen for the presence of HE and SBP. CONCLUSIONS: To screen cirrhotic patients for SBP, calprotectin should be assessed in ascitic fluid while it should be measured in feces when screening for HE. However, the value of calprotectin in managing individual patients must be considered in the specific clinical context.

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Endurance athletes with intermittent claudication caused by iliac artery stenosis treated by endarterectomy with vein patch--short- and mid-term results.

INTRODUCTION: Endurance athletes may suffer from intermittent claudication. A subgroup of 16% has severe iliac artery stenosis due to endofibrosis. In this study we report the short- and mid-term results of endarterectomy with venous patching. PATIENTS/METHODS: Athletes with claudication-like complaints were analysed using a protocol including cycling test and provocative echo-Doppler. Thirty-six athletes were diagnosed with serious iliac flow limitation (one bilateral), confirmed by additional magnetic resonance (MR) angiography. Endarterectomy with venous patching was performed for 32 iliac artery stenosis and five occlusions. Postoperative (mean 15.6 months) 33 legs were evaluated using the same diagnostic protocol. A complete follow-up after mean 29 months was obtained by questionnaire. RESULTS: Twenty-eight athletes were symptom free or could perform on a desired level with minor remaining complaints. Two athletes were satisfied though minor complaints prohibited high competition performance. Two athletes developed a re-stenosis and became symptom free after an additional operation. Three athletes had objective improvement but limited decrease in symptoms. One was unsatisfied but refused postoperative tests. The only major surgical complication was a postoperative bleeding necessitating re-operation. Postoperative tests showed significant increase in maximal workload and post-exercise ankle-brachial index. No aneurysm formation was detected. CONCLUSIONS: Precise diagnosis and meticulously performed endarterectomy with vein patching have satisfactory results in mid-term follow-up with acceptable risk in endurance athletes complaining of intermittent claudication due to iliac artery stenosis.

Effective surgical treatment of the carotid sinus sindrome.

Elderly patients frequently suffer from dizziness and syncope; however, an underlying disease may not always be identified. Three patients aged 69, 71 and 56, respectively, experienced spells of dizziness and syncope. Massage of the carotid sinus demonstrated the presence of a carotid sinus syndrome (CSS), an abnormal baroreflex response of the carotid sinus that leads to asystole and extreme hypotension. Conventional treatment is generally by insertion of a pacemaker. These patients, however, were referred to the vascular surgery department of our hospital for removal of adventitial layers of proximal portions of the internal carotid artery. Recovery was uneventful; all three are now free of symptoms. CSS should be considered in the differential diagnosis of dizziness and syncope. Surgical denervation of the carotid artery is a valid treatment option, especially in the vasodepressive or mixed type of CSS.

[Diagnostic image (398). A man with swollen elbows]. / Diagnose in beeld (398). Een man met gezwollen ellebogen.

A 28-year-old male haemodialysis patient presented with bilateral swollen elbows due to tumoral calcinosis.

Abberant sex habits leading to acute limb ischemia and hematuria.

We report a case of a 42 year-old man suffering from an acute limb ischemia. Upon urokinase treatment he developed gross hematuria. Finally, CT scanning revealed a self-inserted foreign body not only causing thrombosis of the external iliac artery, but also forming an arteriovesical fistula. This case emphasises the importance of detailed history taking and thorough further investigation in recurrent macroscopic hematuria in a patient. Massive bleeding from the bladder should alert the doctor for a rare, but life-threatening arteriovesical fistula.

Recognising vascular causes of leg complaints in endurance athletes. Part 2: the value of patient history, physical examination, cycling exercise test and echo-Doppler examination.

UNLABELLED: Leg complaints at maximal exercise in endurance athletes may have many causes, including arterial flow limitations in the iliac arteries. Such flow limitations can evolve into serious health problems due to increasing intravascular obstruction or even complete obstruction as a result of dissection or thrombosis. Early detection is therefore of clinical importance, but conventional diagnostic tools often prove inadequate. In the current study simple sports-specific tests are examined for their diagnostic power. Test variables derived from patient history, physical examination, cycling exercise testing followed by arterial pressure measurements at the ankle, and echo-Doppler examination with provocative manoeuvres were tested in 92 symptomatic legs (80 patients). A validated clinical classification acted as a reference. Several test variables proved useful. However, no single test variable combined a high sensitivity with a high specificity. Multivariate testing resulted in the correct classification of 91 % of patients, reaching a sensitivity of 0.90 and specificity of 0.93 (kappa 0.76). Four patients wrongly classified as non-vascular suffered from kinking in the common iliac artery that could not be visualised using the diagnostic tools currently available in this study. IN CONCLUSION: simple sports-specific tests accurately diagnose iliac artery obstruction in endurance athletes.

Recognising vascular causes of leg complaints in endurance athletes. Part 1: validation of a decision algorithm.

Flow limitations in the iliac arteries of endurance athletes during exercise were previously ascribed solely to intravascular lesions. We postulate that functional kinking of the arteries can also result in flow limitations. However, the diagnostic tools in routine practice are not effective in diagnosing such flow limitations in a substantial proportion of athletes, mainly because these diagnostic tools do not measure in the provocative situations. Ninety-two symptomatic legs in 80 endurance athletes were examined with newly developed, sports-specific vascular tests. Thirty-five asymptomatic cyclists matched for working capacity served as the control subjects. Legs were classified as vascular or non-vascular following a decision algorithm, based upon the results of these diagnostic tests, excluding orthopaedic causes by the effects of specific treatment. Independently of this clinical classification, an alternative method was applied to find stable characteristics in the total patient group using factor analysis. This characterisation was based on scores on 14 test variables deriving from diagnostic tests that were not used in the decision algorithm, thus avoiding dependency between the clinical categorisation and the statistical categorisation. The hypothesis was that these characteristics were sufficiently sensitive to classify patients with vascular and non-vascular complaints. If so, these characteristics should correspond with the one derived from the decision algorithm. Following the decision algorithm, 58 legs (63%) were classified as vascular, 29 (32%) as non-vascular and 5 (5%) as inconclusive. The latter were considered non-vascular. In a substantial proportion of the vascular patients, kinking of the iliac arteries was identified as the major cause of flow limitation. The characteristics derived from factor analysis proved to classify 87% in agreement with the decision algorithm (kappa 0.56). The agreement is sufficient for validation of the clinical classification. The algorithm can therefore be applied in clinical situations to diagnose endurance athletes with flow limitations due to both intravascular lesions and kinking of the arteries.

Detection and treatment of claudication due to functional iliac obstruction in top endurance athletes: a prospective study.

BACKGROUND: Endurance athletes often have restrictions in flow in their iliac arteries during exercise. Such restrictions have previously been ascribed solely to intravascular lesions. We postulate that flow could also be restricted by functional kinking in the arteries, and that surgical release of these kinks might be an effective treatment. METHODS: We prospectively studied 80 endurance athletes who had complaints suggestive of flow restriction in the iliac arteries of one (n=74) or both (6) legs (total 92 legs). Using vascular diagnostic tools, we examined athletes while they were doing activities that often provoke flow restrictions. Restrictions were determined by measurement of systolic pressure in the ankle after exercise; peak systolic velocities were measured with echo-doppler. Kinks were detected with echo-doppler and magnetic-resonance angiography. When functional kinking was diagnosed as the cause of the restriction, the athlete was offered surgery to release the iliac arteries, as part of our prospective study. FINDINGS: We recorded flow restrictions in the iliac arteries of 58 of 92 (63%) legs. In 40 of these legs (69%), kinks were the most important cause of the restriction, making these legs suitable for surgical release. We operated on 23 of 58 (40%) legs. All athletes who had an operation subjectively improved. Maximum workload in a cycling test and ankle pressure significantly improved after the operation. 20 (87%) athletes were able to successfully return to their desired high level of competition. INTERPRETATION: Our sports-specific protocol is effective in detecting kinking of the iliac arteries as a cause for flow restriction in athletes who have few intravascular abnormalities when investigated with conventional vascular diagnostic tools. Surgical treatment directed at the kinking was less invasive and therefore a better alternative to vascular reconstruction in these athletes.

Color Doppler used to detect kinking and intravascular lesions in the iliac arteries in endurance athletes with claudication.

OBJECTIVE: In endurance athletes, flow limitations in the iliac arteries are commonly ascribed to mechanically induced intravascular lesions (endofibrosis). We hypothesize that kinking of the vessels, occurring during exercise, can also cause such flow limitations. Conventional diagnostic tests fail to demonstrate such kinking. METHODS: In the current study, the iliac arteries were examined in 50 endurance athletes suffering from flow limitations in the iliac arteries with color Doppler using provocative maneuvers of hip flexion, isometric psoas contraction and exercise. Five had both-sided complaints resulting in 55 symptomatic legs and 45 asymptomatic legs. Sixteen national level competitive cyclists served as control subjects resulting in 32 healthy reference legs. RESULTS: The iliac arteries could be visualized accurately in 127/132 (96%) of the legs. The legs with insufficient image quality were not scored in the further analysis. In the external iliac artery, kinks were detected in 21/54 symptomatic legs (39%) compared to none in 28 reference legs. Intravascular lesions could be detected in 33/54 symptomatic legs (61%) compared to only 1/28 reference legs (4%). In the symptomatic legs Doppler measurements showed significantly higher peak systolic velocities in all test conditions compared to the reference legs (P<0.05). These differences increased significantly with provocative maneuvers (P<0.05).In the common iliac artery, kinks were demonstrated in 3/54 symptomatic legs (6%) and an intravascular lesion in 2/54 symptomatic legs (4%) only. Neither kink nor intravascular lesions were demonstrated in the reference legs. Peak systolic velocity measurements in the common iliac artery were in line with these observations and did not show differences between symptomatic and reference legs. The incidence of intravascular lesions in the external and common iliac artery is as expected, however, the incidence of kinks in the common iliac artery is much lower than reported from magnetic resonance angiography. This discrepancy is most probably caused by the fact that kinks in the common iliac artery are predominantly situated in the coronal plane, which cannot be visualized by color Doppler. CONCLUSION: Both kinks and intravascular lesions are associated with flow limitations in the iliac arteries in endurance athletes. Color Doppler appears to be an effective technique to visualize and scale kinks and intravascular lesions in the external iliac artery and to visualize and scale intravascular lesions in the common iliac artery.

CpsB is a modulator of capsule-associated tyrosine kinase activity in Streptococcus pneumoniae.

Tyrosine phosphorylation is associated with polysaccharide synthesis in a number of Gram-positive and Gram-negative bacteria. In Streptococcus pneumoniae, CpsB, CpsC, and CpsD affect tyrosine phosphorylation and are critical for the production of a mature capsule in vitro. To characterize the interactions between these proteins and the phosphorylation event they modulate, cps2B, cps2C, and cps2D from the capsule type 2 S. pneumoniae D39 were cloned and expressed both individually and in combination in Escherichia coli. Cps2D purified from E. coli was not phosphorylated unless it was co-expressed with its cognate transmembrane domain, Cps2C. Purified phosphorylated Cps2D had tyrosine kinase activity and could phosphorylate both dephosphorylated Cps2D and an exogenous substrate (poly-Glu-Tyr) in the absence of ATP. Cps2B exhibited phosphatase activity against both purified phosphorylated Cps2D and p-nitrophenyl phosphate. An additional role for Cps2B as an inhibitor of Cps2D phosphorylation was demonstrated in both co-expression experiments in E. coli and in vitro experiments where it blocked the transphosphorylation of Cps2D even in the presence of the phosphatase inhibitor sodium orthovanadate. cps2C and cps2D deletion mutants in S. pneumoniae produced no detectable mature capsule during laboratory culture. Both were avirulent in systemic mouse infections and were unable to colonize the nasopharynx, suggesting that the failure to produce capsule was not dependent on the environment. Based on these results, we propose a model for capsule regulation where CpsB, CpsC, CpsD, and ATP form a stable complex that enhances capsule synthesis.

Magnetic resonance angiography used to detect kinking in the iliac arteries in endurance athletes with claudication.

In endurance athletes, leg complaints upon maximal exercise caused by flow limitations in the iliac arteries are frequently encountered. We theorize that functional kinking of the vessels, which occurs especially during hip flexion, may be a cause for such flow limitations. Conventional diagnostic tests cannot demonstrate such kinkings. Using gadolinium-enhanced magnetic resonance angiography, a 3D dataset of the aorto-iliac arteries could be obtained with the hips flexed. An image processing procedure was developed using a new segmentation algorithm to be able to use standard surface rendering techniques to visualize the arteries with an improved 3D appearance. These techniques were applied in the current study in 42 endurance athletes with documented flow limitations in the iliac arteries. As a control group 16 national level competitive cyclists without flow limitations in the iliac arteries were studied. Forty-six affected legs were examined in 42 patients. In all patients and reference persons image quality was adequate and the segmentation algorithm could be applied. In 22 affected legs (48%) a kinking in the common iliac artery could be demonstrated, compared with one leg (3%) in the control group. In 13 affected legs (28%) a kinking in the external iliac artery could be demonstrated, compared with three legs (9%) in the control group. It can be concluded that flow limitations in the iliac arteries in endurance athletes are associated with kinkings in the common and/or the external iliac arteries. Magnetic resonance angiography with the hips flexed followed by this newly developed segmentation algorithm is effective to visualize and score these kinkings.

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.

Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These molecules are active in both 293 HEK cells and neuronal cultures, and exert their effect upon A beta production without affecting protein secretion, most notably in the secreted forms of the amyloid precursor protein (APP). Oral administration of one of these compounds, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, to mice transgenic for human APP(V717F) reduces brain levels of Ass in a dose-dependent manner within 3 h. These studies represent the first demonstration of a reduction of brain A beta in vivo. Development of such novel functional gamma-secretase inhibitors will enable a clinical examination of the A beta hypothesis that Ass peptide drives the neuropathology observed in Alzheimer's disease.

Flow limitations in the iliac arteries in endurance athletes. Current knowledge and directions for the future.

Pain and powerless feeling in the leg during cycling may indicate a serious problem that limits the performance in cyclists. Apart from the well-known muscular and neurological origin, such complaints can also be attributed to flow limitations in the iliac arteries caused by functional lesions (kinking and/or excessive length of vessels) and/or intravascular lesions (endofibrosis). Reliable insight in the prevalence is lacking. Most intravascular lesions (approximately 90%) are located in the external iliac artery. The diagnosis is frequently missed because physiotherapists and medical doctors are often unacquainted with the problem. The only finding in physical examination, discriminating for a vascular problem, is a bruit in the inguinal region with the thigh maximally flexed. Available diagnostic techniques are proven to be inadequate for this specific lesion, which has characteristics other than those of atherosclerotic lesions. Moreover, common techniques in a vascular laboratory do not incorporate the specific sport conditions necessary for provoking the complaints. Provocative testing on a bicycle ergometer with high intensity of exercise, combined with postexercise blood pressure measurements (at the ankle of both legs, or the ankle to arm pressure ratio) is used. Imaging techniques (echo-doppler, arterial digital subtraction angiography, magnetic resonance imaging and angiography) are necessary for proper classification of the problem. The application of specific provoking manoeuvres (hip flexion, psoas contraction, high-intensity exercise) in combination with these imaging techniques prove to be potentially valuable, although the diagnostic accuracy has to be established. Treatment should be tailored to the specific problems of the individual patient. Conservative treatment mainly indicates an advice to change sports activity. Surgical mobilization of the iliac arteries for functional lesions, and vascular reconstructions in case of intravascular lesions are possible, although long-term follow-up is lacking. Percutaneous transluminal angioplasty and intravascular stent are contra-indicated because of high risks for dissection and reactive intimal hyperplasia, respectively.

Acute abdomen in mentally retarded patients: role of aerophagia. Report of nine cases.

Between 1993 and 1996 nine mentally retarded patients presented because of an acute abdomen. All had the habit of aerophagia, diagnosed previously by a general practitioner. Massive distension of the bowel led to ileus, volvulus, and necrosis. After placement of a percutaneous endoscopic gastrostomy catheter or performing a gastrostomy during laparotomy with the intention to use as a desufflator, no recurrence of the signs and symptoms of an acute abdomen were observed.

A counterintuitive result in Bell's model of delayed maturity.

Bell formulated a model with constant parameters in which he applied the commonsense argument that delayed maturity would be favored in iteroparous species if fecundity at first episode increased with age at a rate greater than the rate of decline in survival. However, analysis of his model reveals a flaw leading to the counterintuitive result that a geometric increase in fecundity with age cannot be made large enough to offset even a small geometric decline in survival so that population growth rate could increase with age of maturity. Thus, favorable selection of delayed maturity is unlikely in Bell's model. Some age-dependent models are described that avoid this flaw. This analysis extends the models of Sibly and Calow to include the counterintuitive result that an exponential increase in fecundity cannot offset an exponential decline in survival to favor delayed reproduction at any age.

The Gracz arteriovenous fistula evaluated. Results of the brachiocephalic elbow fistula in haemodialysis angio-access.

OBJECTIVES: To assess fistula patency and complication rates in braciocephalic elbow fistulas of both the Gracz and the side-to-side configuration. DESIGN: Retrospective clinical study. METHODS: Life table patency and complications of 50 Gracz fistulas and 23 side-to-side elbow fistulas created between 1988 and 1993 were reviewed. RESULTS: The cumulative patency for the elbow fistulas was 84% after 1 year and 78% after 3 years. No difference was found between the Gracz fistula and the side-to-side elbow fistula. Stenosis was the most frequent indication for revision and thrombosis was the most frequent cause of fistula failure. CONCLUSION: The elbow fistula has a long patency with few complications and performs as well as wrist fistulas and better than the graft fistulas reported in the literature. The Gracz elbow fistula has results as good as the side-to-side elbow fistula. Graft fistulas should be reserved for tertiary procedures only.

The brachiocephalic elbow fistula: a useful alternative angioaccess for permanent hemodialysis.

PURPOSE: Wrist fistulas are increasingly difficult to establish in the aging hemodialysis population. We assessed fistula patency and occlusion rate in elbow fistulas compared with wrist and graft fistulas. METHODS: We analyzed all 104 fistulas created in all 68 patients who underwent hemodialysis during October 1993 at the St. Joseph General Teaching Hospital, Veldhoven, The Netherlands. Life-table patency and complications were analyzed for 31 elbow fistulas, 56 wrist fistulas, and 17 polytetrafluoroethylene or saphenous vein graft fistulas. RESULTS: The patency rate for elbow fistulas was 93% at 1 year and 80% at 3 years. Wrist fistulas had a patency rate of 76% at 1 year and 65% at 3 years. Graft fistulas had a poorer patency rate: 69% at 1 year and 62% at 3 years. There were significantly more failures in the wrist fistulas (p < 0.02). Thrombosis accounted for most fistula failures. Venous stenosis was the most frequent indication for revision. The high incidence of concomitant diseases was not related to fistula outcome. CONCLUSIONS: The elbow fistula performed better than the wrist fistula. Liberal use of the elbow fistula is justified, especially when the epifascial veins or the radial artery at the wrist is in poor condition. Graft fistulas should be reserved for tertiary procedures.