Celiac axis stenosis and digestive disease: Diagnosis, consequences and management.

Arterial blood flow to the organs of the upper abdomen is provided by the celiac axis (CA) and the superior mesenteric artery (SMA) that communicate between each other via the gastro-duodenal artery, the anterior and posterior pancreatico-duodenal arcades, the branches of the dorsal pancreatic artery and inconsistently, though a supplementary arcade that connects the CA and the SMA (arcade of Bühler). Celiac axis stenosis may or may not have a hemodynamic impact on the splanchnic circulation. Hemodynamically significant CA stenosis can be asymptomatic, or symptomatic with variables clinical consequences. Management depends on whether the mechanism of stenosis is extrinsic or intrinsic. When upper gastrointestinal interventional radiology or surgery is indicated, stenosis can pose technical difficulties or create severe ischemia requiring good understanding of this entity in the planning of operative steps and adapted management. Management of CA stenosis is therefore multidisciplinary and may involve interventional radiologists, gastrointestinal surgeons, vascular surgeons as well as medical physicians. Even though the prevalence of CA stenosis is relatively low (between 5 and 10%) and irrespective of its etiology, surgeons, radiologists and physicians must be aware of it because it can intervene in the management of upper gastrointestinal disease. It must be sought, and treatment must be adapted to each particular situation to avoid potentially severe complications.

Surgical technique for placement of the automated low flow ascites pump (Alfapump).

Approximately 10% of patients with ascites associated with cirrhosis fail to respond to dietary rules and diuretic treatment and therefore present with refractory ascites. In order to avoid iterative large-volume paracentesis in patients with contraindication to TIPS, the automated low flow ascites pump system (Alfapump) was developed to pump ascites from the peritoneal cavity into the urinary bladder, where it is eliminated spontaneously by normal micturition. This manuscript reports the surgical technique for placement of the Alfapump.

A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts.

Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10-5 ). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.

Early removal of intraperitoneal drainage after pancreatoduodenectomy in patients without postoperative fistula at POD3: Results of a randomized clinical trial.

BACKGROUND: To determine whether the timing of removal of abdominal drainage (AD) after pancreatoduodenectomy (PD) influences the 30-day surgical site infection (30-day SSI) rate. METHODS: A multicenter randomized, intention-to-treat trial with two parallel arms (superiority of early vs. standard AD removal on SSI) was performed between 2011 and 2015 in patients with no pancreatic fistula (PF) on POD3 after PD (NCT01368094). The primary endpoint was the 30-day SSI rate. The secondary endpoints were specific post-PD complications (grade BC PF), postoperative morbidity and risk factor of SSI, reoperation rate, 30-day mortality, length of drainage, length of stay and postoperative infectious complications. RESULTS: One hundred and forty-one patients were randomized: 71 in the early arm, 70 in the standard arm (70.2% of pancreatic adenocarcinomas; 91.5% of pancreatojejunostomies; 66.0% of bilateral drainages; feasibility: 39.9%). Early removal of drains was not associated with a significant decrease of 30-day SSI (14.1% vs. 24.3%, P=0.12). A lower rate of deep SSI was observed in the early arm (2.8% vs. 17.1%, P=0.03), leading to a shorter length of stay (17.8±6.8 vs. 21.0±6.1, P=0.01). Grade BC PF rate (5.6%), severe morbidity (17.7%), reoperation rate (7.8%), 30-day mortality (1.4%) and wound-SSI rate (7.8%) were similar between arms. After multivariate analysis, the timing of AD removal was not associated with an increase of 30-day SSI (OR=0.74 [95% CI 0.35-1.13, P=0.38]). CONCLUSION: In selected patients with no PF on POD3, early removal of abdominal drainage does not seem to increase or decrease surgical site infection's occurrence.

[Oseltamivir in pregnancy, lactation and neonatal period--comparison of international recommendations]. / Oseltamivir im Wochenbett - Vergleich internationaler Empfehlungen.

BACKGROUND: In the current influenza A (H1N1) pandemia, data on neonatal and maternal Oseltamivir chemoprophylaxis and treatment are limited. Recommendations of national and international health authorities do not compensate for a lack of controlled studies on pharmacokinetics and safety. However, the level of consent may contribute to individual clinical decisions. METHODS: We have reviewed online recommendations by health authorities in the context of the current literature. RESULTS: Given the limited database, there is a high level of consent among recommendations issued by health authorities regarding treatment with Oseltamivir and breast-feeding. DISCUSSION: The majority of recommendations do not regard treatment with Oseltamivir as a contraindication to breast-feeding. Antiviral chemoprophylaxis of influenza A (H1N1) infection in preterm infants is not recommended due to the lack of data on its pharmacokinetics and safety. CONCLUSION: Variable recommendations have been issued regarding the choice of neuraminidase inhibitors in pregnancy. Additional information on the pharmacokinetics and safety of neuraminidase inhibitors for breast-feeding mothers and neonates is essential in order to address potential future pandemics.

Reduction of nontarget infection and systemic toxicity by targeted delivery of conditionally replicating viruses transported in mesenchymal stem cells.

The fiber-modified adenoviral vector Delta-24-RGD (D24RGD) offers vast therapeutic potential. Direct injection of D24RGD has been used to successfully target ovarian tumors in mice. However, systemic toxicity, especially in the liver, profoundly limits the efficacy of direct viral vector delivery. Mesenchymal stem cells (MSC) have the ability to function as a vector for targeted gene therapy because of their preferential engraftment into solid tumors and participation in tumor stroma formation. We show that MSC-guided delivery of D24RGD is specific and efficient and reduces the overall systemic toxicity in mice to negligible levels compared with D24RGD alone. In our model, we found efficient targeted delivery of MSC-D24RGD to both breast and ovarian cell lines. Furthermore, immunohistochemical staining for adenoviral hexon protein confirmed negligible levels of systemic toxicity in mice that were administered MSC-D24RGD compared with those that were administered D24RGD. These data suggest that delivery of D24RGD through MSC not only increases the targeted delivery efficiency, but also reduces the systemic exposure of the virus, thereby reducing overall systemic toxicity to the host and ultimately enhancing its value as an anti-tumor therapeutic candidate.

[Unilateral pulmonary agenesis, aplasia and dysplasia]. / Unilaterale pulmonale Agenesie, Aplasie und Dysplasie.

Unilateral pulmonary anomalies are rare events of unknown etiology and large clinical variability. Neonatal history does not allow for a reliable prognosis. Interdisciplinary mangament includes prenatal diagnostics and obstetrics, genetics, neonatology, pediatric cardiology and surgery as well as pediatric orthopedics. Neonatal history and long-term follow-up in three patients are presented here including a discussion of prenatal diagnostics and the embryo-genetic basics of lung development. In three term neonates the diagnoses of unilateral pulmonary agenesis, aplasia and dysplasia, respectively, were based on angiography, MRI and bronchoscopy. Neonatal presentation and long-term consequences were studied in the context of the current literature. Neonatal complications ranged from mild repiratory distress to pulmonary failure requiring mechanical ventilation. One patient developed scoliosis on long-term follow-up. Cardiac failure or pulmonary hypertension did not occur during follow-up, in one case lung malformation was accompanied by VACTER-association. Unilateral lung malformation is frequently associated with other, singular or complex anomalies (e.g., renal and vascular). A possible relationship to disrupted regulation of embryo-genetic factors such as T-BOX genes, PITX2 and growth factors ( FGF10), which regulate ASYMMETRICAL pulmonary morphogenesis is discussed. Disruptive unilateral pulmonary malformations may serve as a model for embryological lung development and other anomalies (e.g., congenital diaphragmatic hernia, unilateral hypoplasia and CCAM). Prenatal diagnosis is characterized by unilateral hyperechogenicity of the affected lung. Neonatal presentation is determined by mediastinal shift which may be corrected by tissue-expander implantation. Associated anomalies require cytogenetic analysis and sequencing of currently known mutations. Long-term follow-up by echocardiography and pulmonary function testing is mandatory in these patients.

Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells.

Mesenchymal stem cells (MSC) exhibit tropism for sites of tissue damage as well as the tumor microenvironment. Many of the same inflammatory mediators that are secreted by wounds are found in the tumor microenvironment and are thought to be involved in attracting MSC to these sites. Cell migration is dependent on a multitude of signals ranging from growth factors to chemokines secreted by injured cells and/or respondent immune cells. MSC are likely to have chemotactic properties similar to other immune cells that respond to injury and sites of inflammation. Thus, the well-described model of leukocyte migration can serve as a reasonable example to facilitate the identification of factors involved in MSC migration. Understanding the factors involved in regulating MSC migration to tumors is essential to ultimately develop novel clinical strategies aimed at using MSC as vehicles to deliver antitumor proteins or suppress MSC migration to reduce tumor growth. For example, radiation enhances inflammatory signaling in the tumor microenvironment and may be used to potentiate site-specific MSC migration. Alternatively, restricting the migration of the MSC to the tumor microenvironment may prevent competent tumor-stroma formation, thereby hindering the growth of the tumor. In this review, we will discuss the role of inflammatory signaling in attracting MSC to tumors.

Lipopolysaccharide binding protein in preterm infants.

OBJECTIVE: To assess serum concentrations of lipopolysaccharide binding protein (LBP) in preterm infants with neonatal bacterial infection (NBI). METHODS: Blood samples were analysed of 57 preterm (28(+1) to 36(+6), median 33(+2) weeks gestation) and 17 term infants admitted to the neonatal intensive care unit within the first 72 hours of life with suspicion of NBI. Samples were obtained at first suspicion of sepsis and after 12 and 24 hours. Diagnosis of NBI was confirmed by raised concentrations of C reactive protein and/or interleukin 6. The influence of gestational age and labour was analysed. RESULTS: Maximum LBP concentrations in infants with NBI were greatly increased compared with infants without NBI (13.0-46.0 microg/ml (median 20.0 microg/ml) v 0.6-17.4 microg/ml (median 4.2 microg/ml)). LBP concentrations in infected infants were not yet significantly raised when NBI was first suspected. The LBP concentrations of preterm infants were comparable to those of term infants. Regression analysis revealed no significant effect of labour or gestational age on LBP. CONCLUSIONS: Raised LBP concentrations indicate NBI in preterm and term infants. Preterm infants of > 28 weeks gestation seem to be capable of producing LBP as efficiently as term infants. Neonatal LBP concentrations are not influenced by labour. LBP may be a useful diagnostic marker of NBI in preterm infants.

Modification of cord blood IL-6 production with IgM enriched human immunoglobulin in term and preterm infants.

Pro-inflammatory cytokines contribute significantly to the morbidity of premature infants. IL-6 and IL-8 are involved in the pathogenesis of pulmonary and cerebral tissue injury. The effect of human immunoglobulin preparations on cytokine production in preterm infants has not been studied. We investigated the influence of immunoglobulin on LPS stimulated IL-6 and IL-8 production in cord blood of healthy preterm neonates. Ten non-infected preterm infants delivered by cesarean section and 5 healthy term neonates were included. In the preterm infants, significant IL-6 production was observed in the absence of immunoglobulin after 4 h [median 113 (39-725) pg/ml], 8 h [375 (234-1795) pg/ml] and 12 h [360 (248-2765) pg/ml] of LPS incubation. IL-6 concentrations were significantly lower after incubation with LPS+immunoglobulin after 4 h [median 38 (5-568) pg/ml; p=0.005], 8 h [178 (10-1830) pg/ml; p=0.001] and 12 h [182 (29-2530) pg/ml; p=0.002]. Cultures from term infants produced IL-6 levels approx. 4 times of those from premature infants unaffected by immunoglobulin. IL-8 production also correlated to gestational age and was not affected by immunoglobulin in both groups. Human immunoglobulin preparation may modify IL-6 production in cord blood cultures from premature infants.

Increased serum levels of interleukin 6 are associated with severe intraventricular haemorrhage in extremely premature infants.

BACKGROUND: Intraventricular haemorrhage (IVH) and periventricular leucomalacia (PVL) in premature infants presumably have many causes. It has been proposed that inflammatory processes in the fetomaternal unit play an important role in the pathogenesis of these lesions. OBJECTIVE: To study the correlation of postpartum serum interleukin 6 (IL6) concentration as a marker of inflammation and neonatal cerebral morbidity in preterm infants < 28 weeks of gestational age. METHODS: A total of 88 infants were grouped according to maximum serum IL6 levels within 12 hours post partum: group A (n = 50), < or = 100 pg/ml; group B (n = 38), > 100 pg/ml. Ultrasound studies and clinical assessment were performed routinely. RESULTS: IVH was noted significantly more often in group B (24/38; 63%) than in group A (19/50; 38%) (p = 0.02). In a multiple logistic regression model, raised serum IL6 independently predicted development of severe IVH (odds ratio 8.4; 95% confidence interval 2.85 to 24.9; p = 0.0001). CONCLUSIONS: Raised serum IL6 may serve as a marker for severe IVH in infants < 28 weeks of gestational age. Although cerebral morbidity in premature infants is determined by different variables, the identification of systemic inflammation can help to define the need for anti-inflammatory strategies to prevent cerebral morbidity.

Long term follow up of serostatus after maternofetal parvovirus B19 infection.

BACKGROUND: Maternofetal parvovirus B19 infection may result in fetal hydrops or abortion. Chronic infection has been associated with long term complications (polyarthritis, persistent aplastic anaemia, hepatitis). In pregnancy maternal immunosuppression caused by a TH2 dominant response to viral antigens has been observed. There is little information on long term reactivity to intrauterine infection. AIMS: To assess the serological status in children and their mothers after maternofetal parvovirus B19 infection and development of fetal hydrops. METHODS: A total of 18 children and their mothers, and 54 age matched control infants were studied. Main outcome measures were parvovirus B19 DNA, specific IgM and IgG against the virus proteins VP1/VP2, and NS-1 in venous blood. RESULTS: Parvovirus B19 DNA and antiparvovirus B19 (IgM) were undetectable in all sera. A significant larger proportion of maternal sera compared to study children's sera contained IgG against the non-structural protein NS-1. Mean levels of VP1/VP2 IgG antibodies were significantly lower in the children than in their mothers (48 (36) v 197 (95) IU/ml). There was no history of chronic arthritis in mothers and children. Five women had subsequent acute but transient arthritis postpartum, which was not correlated with antibodies against NS-1. CONCLUSIONS: Serological evidence of persistent infection after maternofetal parvovirus B19 disease could not be detected. Increased maternal prevalence of anti NS-1 (IgG) and increased levels of antiparvovirus B19 (IgG) may reflect prolonged viraemia compared to fetal disease.

Neurodevelopmental outcome after intrauterine red cell transfusion for parvovirus B19-induced fetal hydrops.

OBJECTIVE: To assess long term neurodevelopmental outcome of children after intrauterine intravascular red cell transfusion (JUT) for Parvovirus B19-induced fetal hydrops. DESIGN: Data of study children were investigated retrospectively. Neurodevelopmental evaluation was performed by appropriate standard tests (Griffiths, Snijders-Oomen, Kaufmann Assessment Battery for Children tests). SETTING: Tertiary care university teaching hospital. SAMPLE: Twenty children who had Parvovirus-induced fetal hydrops and intrauterine transfusion of packed red blood cells (IUT). METHODS: Retrospective chart analysis and standard neurodevelopmental testing. MAIN OUTCOME MEASURES: Developmental quotient (DQ) and intelligence quotient (IQ) according to the age at testing. RESULTS: Twenty survivors of Parvovirus B19-induced fetal hydrops successfully treated by IUT were followed until 13 months to nine years of age. On clinical follow up, no neurologic sequelae were evident. Neurodevelopmental scores of all children ranged within two standard deviations of a normal population (median 101, range 86-116) and exceeded one standard deviation in three children. There was no significant neurodevelopmental delay. CONCLUSION: Children having survived successful IUT for Parvovirus B19-induced fetal anaemia and hydrops have a good neurodevelopmental prognosis. Our results support the use of IUT for correction of Parvovirus B19-induced fetal anaemia and subsequent hydrops.

CT imaging of pulmonary lobar interstitial emphysema in a spontaneous breathing preterm infant.

Pulmonary interstitial emphysema (PIE) is a well-recognized severe complication of neonatal respiratory distress syndrome (RDS). However, its occurrence under spontaneous breathing conditions has been described rarely. We present a case of PIE of the left upper lung lobe in an extremely low birth weight infant. Recurrent episodes of spontaneous pneumothorax led to the diagnosis, which was confirmed by histopathology. Plain chest X-ray did not show typical signs of PIE, whereas extra-alveolar air accumulation could be visualized by helical computed tomography (CT)-scan. We stress the role of predispositional factors increasing the risk of PIE development in spontaneous breathing preterm infants.

Endotoxin-stimulated production of IL-6 and IL-8 is increased in short-term cultures of whole blood from healthy term neonates.

To assess the stimulated production of Interleukin-6 and Interleukin-8 in healthy term neonates compared to adults, and to study the effect of labour on the capacity of cytokine secretion, 20 healthy term neonates (11 delivered by elective caesarean section, (ECS) group; 9 vaginally delivered, (VD) group) were included in the study, and five healthy adult volunteers served as controls. Spontaneous and lipopolysaccharide (LPS)-stimulated IL-6 and IL-8 secretion in short-term umbilical whole blood cultures was determined. Spontaneous IL-6 (IL-8) secretion was detected in only a few samples with maximum levels of 14 (23) pg/ml. After 4 h of LPS incubation median IL-6 levels increased to 2026 (339-2547) pg/ml (VD group) and 1670 (704-2037) pg/ml (ECS group). Median IL-8 concentration after LPS stimulation was 2142 (738-4053) pg/ml in the VD group and 1483 (1036-2934) pg/ml ECS group. Interleukin-6 and IL-8 levels following LPS-stimulation in both groups markedly exceeded the values of adult controls. Stimulated cytokine secretion showed no significant difference between VD and ECS groups. Spontaneous cytokine production in cord blood is variable and related to individual cytokine expression and regulation. The pro-inflammatory response to endotoxin as determined by ex vivo LPS-stimulation of short-term whole blood cultures of term neonates, in contrast to spontaneous cytokine secretion, exceeds adult levels and appears to be independent of the mode of delivery and labour.

Cell-associated interleukin-8 in cord blood of term and preterm infants.

To assess the effect of gestational age and labor on the interleukin-8 (IL-8) concentration in whole cord blood and serum, IL-8 levels were determined simultaneously in cord blood serum and lysate in 134 infants. Following the elimination of some of the samples due to exclusion criteria, the data for 99 uninfected infants (71 term and 28 preterm) and 9 infants with neonatal bacterial infection delivered either vaginally or by elective or emergency cesarean section were analyzed. The effects of labor and gestational age were tested by analysis of variance. IL-8 was not detectable in the serum of 25 infants, whereas IL-8 levels in whole blood were measurable in all of the samples. The median IL-8 conncentrations in whole cord blood lysate were 106 pg/ml (range, 20 to 415 pg/ml) in preterm infants and 176 pg/ml (range, 34 to 1,667 pg/ml) in term infants. In contrast to the IL-8 levels in serum, IL-8 levels in whole blood were reduced after ECS. Gestational age had no independent effect on the IL-8 concentrations in either serum or whole blood; these concentrations increased in infected infants after labor. We conclude that the neonatal proinflammatory response to labor stress was more evident in the concentrations of IL-8 in whole blood than in serum. The levels of IL-8 in whole-blood lysate reflect proinflammatory stimulation in neonates and may be a useful diagnostic tool for the early diagnosis of neonatal infection.