Development Of Severe Complications Research Articles

Результаты резекционных вмешательств на печени на фоне хронической диффузной гепатопатии

Relevance Improvement of the technical aspects of performing liver resections allowed to neutralize the risk of many specific postresection complications. However, among the last until now, post-resection hepatic failure (PHF) remains a difficult problem, which on the background of diffuse changes in the liver, significantly complicates the postoperative period. The purpose of the study To evaluate an influence of concomitant chronic diffuse liver disease on the results of resections performed for benign and malignant focal lesions of the liver. Materials and methods To assess the impact of chronic diffuse liver process in the frequency of complications of liver resections analyzed a control group of patients (81 patients), operated in the department of surgery of the liver and biliary tract and in the department of surgery of portal hypertension and pancreatoduodenal zone during the period from 1998 to 2009. Patients were divided into a group with concomitant diffuse liver disease (chronic viral hepatitis and steatosis) - 53 patients (65.4%) and a group of 28 patients without concomitant liver pathology. Results and their discussion Study the frequency of PHF showed that the development of severe complications in the early postoperative period is clearly correlated with the presence of diffuse liver disease. Thus, in patients without chronic liver diseasePHF occurred in 2 cases against the background of extensive liver resections, which amounted to 7.1% (2/28). In patients with hepatic pathology, the incidence of PHF of varying severity amounted to 18.9% (10/53). The overall incidence of PHF in the study group was 14.8% (12/81). On the background of extensive liver resections PHF complicated the postoperative period, more than twice as often in the presence of chronic liver disease, 28.6% versus 13.3% (8/28 vs. 2/13). At segmental resections PHF occurred only in patients with chronic pathologies in the liver and was 8.0%. The presence of concomitant chronic diffuse liver disease causes a significant decrease in functional status of hepatocytes, which represents a decline of hepatic extraction fraction at 17,1% (67,5 ± 2,3% against 81,4 ± 1,9%) and an increase in half-life of the radiopharmaceutical drop to 26 5% (37,2 ± 1,7 min vs. 29,4 ± 1,2 m) (P <0,001) relative to the group without parenchymatous processes. Conclusion Performing of resection interventions in focal liver disease with chronic diffuse pathology of a liver increases the risk of PHF, which is associated with reduced functional reserve of hepatocytes and slowing compensatory regeneration process.

Intestinal barrier dysfunction in cirrhosis: Current concepts in pathophysiology and clinical implications.

The intestinal lumen is a host place for a wide range of microbiota and sets a unique interplay between local immune system, inflammatory cells and intestinal epithelium, forming a physical barrier against microbial invaders and toxins. Bacterial translocation is the migration of viable or nonviable microorganisms or their pathogen-associated molecular patterns, such as lipopolysaccharide, from the gut lumen to the mesenteric lymph nodes, systemic circulation and other normally sterile extraintestinal sites. A series of studies have shown that translocation of bacteria and their products across the intestinal barrier is a commonplace in patients with liver disease. The deterioration of intestinal barrier integrity and the consulting increased intestinal permeability in cirrhotic patients play a pivotal pathophysiological role in the development of severe complications as high rate of infections, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, variceal bleeding, progression of liver injury and hepatocellular carcinoma. Nevertheless, the exact cellular and molecular mechanisms implicated in the phenomenon of microbial translocation in liver cirrhosis have not been fully elucidated yet.

Impact of HbA1c, followed from onset of type 1 diabetes, on the development of severe retinopathy and nephropathy: the VISS Study (Vascular Diabetic Complications in Southeast Sweden).

HbA1c is strongly related to the development of diabetes complications, but it is still controversial which HbA1c level to strive for in the treatment of type 1 diabetes. The aim of the current study was to evaluate HbA1c, followed from diagnosis, as a predictor of severe microvascular complications and to formulate HbA1c target levels for treatment. A longitudinal observation study followed an unselected population of 451 patients diagnosed with type 1 diabetes during 1983-1987 before the age of 35 years in a region of Southeast Sweden. Retinopathy was evaluated by fundus photography and nephropathy data collected from medical records. HbA1c was measured starting from diagnosis and during the whole follow-up period of 20-24 years. Long-term weighted mean HbA1c was then calculated. Complications were analyzed in relation to HbA1c levels. The incidence of proliferative retinopathy and persistent macroalbuminuria increased sharply and occurred earlier with increasing long-term mean HbA1c. None of the 451 patients developed proliferative retinopathy or persistent macroalbuminuria below long-term weighted mean HbA1c 7.6% (60 mmol/mol); 51% of the patients with long-term mean HbA1c above 9.5% (80 mmol/mol) developed proliferative retinopathy and 23% persistent macroalbuminuria. Long-term weighted mean HbA1c, measured from diagnosis, is closely associated with the development of severe complications in type 1 diabetes. Keeping HbA1c below 7.6% (60 mmol/mol) as a treatment target seems to prevent proliferative retinopathy and persistent macroalbuminuria for up to 20 years.

Highlights in this issue

Highlights in this issue

Severe complications in influenza-like illnesses.

Data on complications from upper respiratory infection are limited. We examined development of severe complications in children presenting to the emergency department (ED) for moderate to severe influenza-like illness (ILI). Prospective cohort study of children 0 to 19 years presenting to a tertiary care children's hospital ED during peak respiratory viral seasons from 2008 to 2010. Subjects included had moderate to severe ILI, defined by performance of venipuncture and nasopharyngeal multiplex polymerase chain reaction for respiratory viruses. Severe complications (respiratory failure, encephalopathy, seizures, pneumonia, bacteremia, death) were prospectively determined. Risk factors for severe complications were collected, including demographics, comorbidities, and household exposures. There were 241 enrolled subjects with median age of 27.4 months (interquartile range 8.9-68.5); 59.3% were boys and 48.5% were black. High-risk conditions were present in 53.5%. Severe complications developed in 35.3% (95% confidence interval [CI] 29.3-41.3), most frequently pneumonia (26.1%). The risk for severe complications was increased in subjects with neurologic or neuromuscular conditions (relative risk 4.0; 95% CI 1.9-8.2). No specific respiratory virus was associated with development of severe complications. Among patients with influenza, severe complications were greater with subtype H1N1 infection (relative risk 1.45, 95% CI 0.99-2.13, P = .048), and were at highest risk for pneumonia (relative risk 4.2, 95% CI 1.2-15.9). In children presenting to the ED for moderate to severe ILI, those with neurologic and neuromuscular disease are at increased risk for severe complications. Development of severe complications did not differ by infecting virus; however, risk of severe complications was greater with subtype H1N1 compared with other influenza.

Acidosis: progression of chronic kidney disease and quality of life.

Metabolic acidosis (MA) is relatively common in patients with chronic kidney disease (CKD) particularly in stages 4 and 5. It is assumed to play a contributory role in the development of several complications including bone disease, skeletal muscle wasting, altered protein synthesis, and degradation. Recent evidence also suggests that even mild acidosis might play a role in progressive glomerular filtration rate loss. Experimental and clinical studies suggest that correction of acidosis by alkali therapy attenuates these complications and improves quality of life. Despite several recent small and single-center studies supporting this notion, more robust evidence is required with regard to the long-term benefits of alkali therapy, type of alkali supplements, and the optimal level of serum bicarbonate.

MTOR inhibitors and renal allograft: Yin and Yang.

Mammalian target of rapamycin inhibitors (mTOR-I), everolimus and sirolimus, are immunosuppressive drugs extensively used in renal transplantation. Their main mechanism of action is the inhibition of cell signaling through the PI3 K/Akt/mTOR pathway. This interesting mechanism of action confers to these medications both great immunosuppressive potential and important anti-neoplastic properties. Although the clinical utility of this drug category, as with other antineoplastic/immunosuppressants, is clear, the use of mTOR-I commonly results in the development of several complications. In particular, these agents may determine severe renal toxicity that, as recent studies report, seems clearly correlated to dose and duration of drug use. The mTOR-I-induced renal allograft spectrum of toxicity includes the enhanced incidence of delayed graft function, nephrotoxicity in particular when co-administered with calcineurin inhibitors (CNI) and onset of proteinuria. The latter effect appears highly frequent in patients undergoing mTOR-I treatment and significantly associated with a rapid graft lost. The damage leading to this complication interests both the glomerular and tubular area. mTOR-I cause an inhibition of proliferation in podocytes and the epithelial-to-mesenchymal transition in tubular cells. Interestingly, all these side effects are mostly reversible and dose related. Therefore, it is unquestionable that these particular drugs should be administered at the lowest dose able to maintain relatively low trough levels, in order to maximize their important and specific therapeutic effects while minimizing or avoiding drug toxicities. Utilization of low dosages of mTOR-I should be encouraged not only in CNI-combined schemas, but also when administered alone in a CNI-free immunosuppressive protocol.

Does Gluten Intake Influence the Development of Celiac Disease–associated Complications?

Celiac disease (CD) is regarded as the most common autoimmune enteropathy in western countries. Epidemiological studies indicate that approximately 1:100 individuals may present with histologically proven CD. CD develops in genetically predisposed subjects after gluten ingestion. It usually subsides after gluten is withdrawn from their diet. Gluten is the only known environmental factor that affects the progression/regression of the intestinal villous atrophy, which is the hallmark of this disease. CD generally follows a benign course after gluten elimination. However, it is also associated with the development of other autoimmune disorders or of intestinal malignancies. The issue of whether such complications, sometimes of significant clinical and prognostic impact, are or are not the result of ongoing gluten ingestion, is an important one that has been investigated over the recent years with conflicting results. In terms of practical implications, the presence of a positive correlation between gluten intake and the development of severe complications would lead to the need for early diagnosis and mass screening. The lack of such correlation would instead suggest a less aggressive diagnostic strategy. This review aims at critically summarizing the evidence supporting either hypothesis.

The Cytokine and Chemokine Profiles in Patients with Hand, Foot and Mouth Disease of Different Severities in Shanghai, China, 2010

Background and purposeSystemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients.MethodWe measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone.ResultsOur present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD.ConclusionWhether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.

Decompensated Cirrhotics Have Slower Intestinal Transit Times as Compared With Compensated Cirrhotics and Healthy Controls

Altered small intestinal motility in cirrhotics may play a major role in the development of bacterial translocation (BT) by leading to small intestinal bacterial overgrowth. BT has been implicated in the development of several complications including spontaneous bacterial peritonitis, esophageal variceal hemorrhage, and hepatorenal syndrome. Prior studies using antroduodenal manometry to evaluate intestinal motility have shown discrepancies regarding the relationship between dysmotility and the severity of cirrhosis. (1) To characterize the frequency of small bowel motility disturbances in cirrhotic patients using a wireless motility capsule (SmartPill); (2) To assess the relationship of intestinal dysmotility with liver disease severity and cirrhosis complications; and (3) To compare intestinal transit times and motility indices among cirrhotics and healthy controls. We conducted a prospective study of 20 patients with cirrhosis (10 compensated, 10 decompensated) who were recruited from Yale New Haven Hospital and Hepatology clinics (February 2011 to July 2011). All patients underwent and completed SmartPill studies. Intestinal transit times were calculated, analyzed, and compared among compensated versus decompensated cirrhotics versus historical, healthy controls. Intestinal transit delays/motility indices were correlated with disease severity and complications. Decompensated cirrhotics had significantly longer small bowel transit times (SBTT) as compared with compensated cirrhotics (6.17 vs. 3.56 h, P=0.036). There was a significant correlation (r=0.77, P=0.0003) between SBTT and cirrhosis severity as assessed by Child-Pugh score. There were no statistical differences noted between the groups for gastric or colonic transit times, although there was a trend toward prolonged transit throughout the gut in decompensated. Cirrhotics with spontaneous bacterial peritonitis and ascites also had significantly longer SBTT as compared with those without. This study demonstrates that decompensated cirrhotics have slower intestinal transit times as compared with compensated cirrhotics and healthy controls. Additional prospective studies are needed to further characterize dysmotility in cirrhotics and its relationship to complications related to BT. This would aid in the identification of patients at risk for developing severe complications and who may benefit from prophylactic prokinetic and/or antimicrobial therapy.

URGENT PROPHYLAXIS, PATHOGENETIC TREATMENT AND PREVENTION OF COMPLICATIONS OF INFLUENZA AND ACUTE RESPIRATORY INFECTIONS IN CHILDREN

Influenza — is an acute viral infection, transmitted by droplet contact. Influenza virus is characterized by its ability to provoke yearly seasonal epidemics, which have great influence on all age populations and are a significant problem for the public health care. This disease can lead to development of severe complications, especially in infants. There are two methods of influenza prophylaxis — specific (vaccination) and non-specific (immunotropic agents). The article contains data on usage of the Russian antiviral agent, which stimulates non-specific protection against influenza virus and other causative agents of respiratory viral infections, especially in infants. A new powder form of the drug which can be used in children from the 1st year of life is represented in the article.

Distinct Deleterious Effects of Cyclosporine and Tacrolimus and Combined Tacrolimus–Sirolimus on Endothelial Cells: Protective Effect of Defibrotide

Endothelial dysfunction seems to be a key factor in the development of several complications observed early after hematopoietic stem cell transplantation (HSCT). The conditioning regimen and many other factors associated with the procedure are responsible for this endothelial damage. The effects of immunosuppressive agents on endothelial function have not been explored in detail. We evaluated the effects of 3 drugs commonly used in HSCT: 2 calcineurin inhibitors, cyclosporine A (CSA) and tacrolimus (TAC), and an inhibitor of mTOR, sirolimus (SIR). We also evaluated the effect of the combination of TAC and SIR (TAC+SIR), which is used increasingly in clinical practice. Microvascular endothelial cells (HMEC-1) were exposed to these drugs to evaluate changes in (1) intercellular adhesion molecule (ICAM)-1 expression on the cell surface, assessed by immunofluorescence labeling and expressed as the mean gray value (MGV); (2) reactivity of the extracellular matrix (ECM) toward platelets, upon exposure of the ECM to circulating blood; and (3) whole-blood clot formation, assessed by thromboelastometry. Studies were conducted in the absence and presence of defibrotide (DF) to assess its possible protective effect. The exposure of HMEC-1 to CSA and TAC+SIR significantly increased the expression of ICAM-1 (157.5 ± 11.6 and 153.4 ± 9.5 MGV, respectively, versus 105.7 ± 6.5 MGV in controls [both P < .05]). TAC applied alone increased ICAM-1 slightly (120.3 ± 8.2 MGV), and SIR had no effect (108.9 ± 7.4 MGV). ECM reactivity increased significantly only in response to CSA (surface covered by platelets of 41.2% ± 5.4% versus 30.1% ± 2.0%, P < .05). DF attenuated all these changes. No significant changes in the viscoelastic properties of clot formation were observed in any condition with blood samples incubated in vitro. In conclusion, CSA and TAC+SIR had a proinflammatory effect, but only CSA exhibited an additional prothrombotic effect. Interestingly, DF exerted clear protective anti-inflammatory and antithrombotic effects on the endothelium.

Third cranial nerve palsy (ptosis, diplopia) accompanied by orbital swelling: case report of unusual clinical presentation of giant cell arteritis associated with polymyalgia rheumatica

IntroductionGiant cell arteritis (GCA) is the most common systemic vasculitis in older individuals, characterized by granulomatosus inflammation of the wall of large and medium-sized arteries. The wide spectrum of arterial sites involved leads to ischemia of different organs resulting in a wide range of clinical signs and symptoms. Temporal artery is commonly involved (temporal arteritis). Unusual patterns of presentation, such as extraocular motility disorders and orbital swelling, may be early and transient manifestations of GCA and precede the permanent visual loss due to ischemic optic neuropathy.Case reportWe describe a patient with uncommon manifestations of GCA consisting of transient recurrent diplopia, ptosis, orbital swelling together with more typical clinical features of the disease such as musculoskeletal manifestations (polymyalgia rheumatica) and facial pain: all signs and symptoms promptly resolved under corticosteroid therapy without relapse.Conclusions A high level of suspicion of GCA in individuals over the age of 50 years is needed to prevent the development of severe complications. Clinicians should be aware of uncommon manifestations of the disease such as head–neck swelling and ophthalmoplegia: management guidelines have stated that prompt administration of adequate dose of corticosteroids as soon as ocular manifestations of GCA are noted may almost totally prevent blindness.

Ptosi palpebrale con diplopia da paralisi del terzo nervo cranico e tumefazione orbitaria: manifestazioni inusuali in un caso di arterite a cellule giganti associata a polimialgia reumatica

Summary Introduction Giant cell arteritis (GCA) is the most common systemic vasculitis in older individuals, characterized by granulomatosus inflammation of the wall of large and medium-sized arteries. The wide spectrum of arterial sites involved leads to ischemia of different organs resulting in a wide range of clinical signs and symptoms. Temporal artery is commonly involved (temporal arteritis). Unusual patterns of presentation, such as extraocular motility disorders and orbital swelling, may be early and transient manifestations of GCA and precede the permanent visual loss due to ischemic optic neuropathy. Case report We describe a patient with uncommon manifestations of GCA consisting of transient recurrent diplopia, ptosis, orbital swelling together with more typical clinical features of the disease such as musculoskeletal manifestations (polymyalgia rheumatica) and facial pain: all signs and symptoms promptly resolved under corticosteroid therapy without relapse. Conclusions A high level of suspicion of GCA in individuals over the age of 50 years is needed to prevent the development of severe complications. Clinicians should be aware of uncommon manifestations of the disease such as head–neck swelling and ophthalmoplegia: management guidelines have stated that prompt administration of adequate dose of corticosteroids as soon as ocular manifestations of GCA are noted may almost totally prevent blindness.

Genetic polymorphisms of antioxidant enzymes in preterm infants

Background: Oxidative stress (OS) is significantly involved in the development of several complications associated with preterm birth, such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) and intraventricular hemorrhage (IVH). Evidence is growing about the associations between single nucleotide polymorphisms (SNPs) in genes involved in OS or antioxidant response and the occurrence of neonatal morbidities. Aim of the study: To assess whether SNPs in genes of superoxide dismutase (SOD) and catalase (CAT), involved in antioxidant pathways, correlate with the occurrence of RDS, BPD, IVH and ROP in preterm neonates. Methods: We performed a retrospective study involving neonates <28 weeks of gestational age. Results: We demonstrated that rs8192287 SOD3 polymorphism is an independent protective factor for IVH, while rs4880 and rs5746136 SOD2 polymorphisms are associated with lower gestational age and birth weight. Haplotypes reconstruction showed that SOD1 (GG) decreased the risk of RDS, IVH and ROP; SOD2 (GT) increased the risk of BPD and decreased the risk of RDS, IVH, and ROP; SOD3 (TGC) decreased the risk of BPD and IVH; and CAT (CTC) decreased the risk of RDS. Conclusions: The study of SNPs or haplotypes reconstruction in genes involved in OS or scavenging activity may be helpful in identifying preterm newborns with a particularly high risk of morbidities, who may benefit from specific prevention strategies.

Cytokine profiles of patients with enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome

Proinflammatory cytokines are related to the pathogenesis of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic-uremic syndrome (HUS). We assessed the kinetics of the release of cytokines such as neopterin, interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α and the soluble forms of type I and II TNF receptors during EHEC O111-induced HUS (EHEC O111/HUS). Fourteen patients with EHEC O111/HUS were enrolled in this study. Serum concentrations of all cytokines other than TNF-α were significantly elevated in patients with severe HUS compared with those in patients with mild HUS. Although serum concentrations of TNF-α were not significantly higher in patients with severe HUS, most patients with acute encephalopathy showed elevated TNF-α levels. Serum concentrations of these cytokines rapidly and markedly increased, and massive hypercytokinaemia developed 1day before the diagnosis of HUS in patients with severe HUS. Changes in the number of white blood cells and concentration of serum lactate dehydrogenase were significantly larger between the onset of hemorrhagic colitis and the time of the diagnosis of HUS in patients with severe HUS compared with those in patients with mild HUS. Proinflammatory cytokines play an important role in the pathogenesis of EHEC infection and development of severe complications, including HUS and encephalopathy. Monitoring the cytokine profile may be useful for assessing disease activity of EHEC O111 infections.

Is it time to draw such a conclusion concerning the use of washed donor blood during paediatric cardiopulmonary bypass?

We read with great interest the recent retrospective series by Boks et al. [1]. The authors concluded that cell saver washing of packed red blood cells (RBCs) does not help prevent hyperkalaemia and hyperlactaemia during paediatric cardiopulmonary bypass (CPB) procedure. Consequently, they did not recommend routinely using this technique during paediatric CPB. However, there are some controversial issues concerning the use of washed RBCs during paediatric CPB: Swindell et al. [2] concluded that cell saver washing of packed RBCs helps prevent hyperkalaemia during CPB but does not prevent hyperlactaemia in paediatric patients; Liu et al. [3] concluded that the levels of potassium, blood glucose and lactate were significantly lower than in the unprocessed group at the beginning and end of CPB. Currently, although smaller circuits and oxygenators have been used for small children and neonates, it is difficult to avoid using donor blood during CPB. Moreover, packed RBCs are an essential part of the CPB priming solution to maintain sufficient oxygen supply in small children and neonates. The storage media in packed RBCs may cause significant acid-base, glucose and electrolyte imbalances, which have been implicated in the development of severe complications [4]. For providing better priming for paediatric patients, many measures have been implemented pre-CPB, such as cell saver and ultrafiltration. In the Boks et al. study, they did not find any benefit in using cell saver to process packed RBCs during CPB. They also suggested that an estimated addition of unwashed RBCs might increase the lactate, K and other measurable variables above acceptable levels. If not, however, pre-washing should not be applied under such specific CPB circumstances. We do not agree with Boks’ opinions. First, their conclusion was based on a retrospective study. Furthermore, they did not compare the results between the two groups regarding postoperative pulmonary function since another recent study [5] reported that washed blood transfusions in cardiac surgery reduced inflammatory biomarkers and may have an impact on post-operative pulmonary function. Consequently, it seems too early to draw such a conclusion based solely on this retrospective study. We think this issue is still under debate and requires a larger number of patients for further clinical investigation to prove whether paediatric patients are benefited by this clinical practice during paediatric CPB.

Seroprevalence of hepatitis-A virus among children aged 1-16 years in Eastern Anatolia, Turkey

This study aims to determine the seroprevalence of hepatitis A among children aged 1-16 years in eastern region of Turkey. The study was conducted at Tunceli State Hospital in Eastern Anatolia, Turkey. Anti-HAV IgM and Anti-HAV IgG antibodies were evaluated among 351 patients admitted to our pediatric policlinic. Anti-HAV IgM and Anti-HAV IgG serologic markers were determined using the ELISA method. The mean age of 351 pediatric patients was 7.5±4.2; of these, 198 (56.4%) were male and 153 (43.6%) were female. A total of 305 (86.9%) cases in this study were seronegative against hepatitis A. Anti-HAV IgG was positive among 46 (13.1%) patients, of these 22 (47.8%) were male and 24 (52.2%) were female. The mean age of seropositive cases was 8.4±4.8. Anti-HAV IgM seropositivity was not detected in the study. The application of a routine hepatitis A vaccine among children will reduce the potential for the development of severe complications. Key words: Hepatitis A, seroprevalence, children, vaccination.

Biomarkers for susceptibility to infection and disease severity in human malaria

Malaria remains a major infectious disease that affects millions of people. Once infected with Plasmodium parasites, a host can develop a broad range of clinical presentations, which result from complex interactions between factors derived from the host, the parasite and the environment. Intense research has focused on the identification of reliable predictors for exposure, susceptibility to infection and the development of severe complications during malaria. Although most promising markers are based on the current understanding of malaria immunopathogenesis, some are also focused more broadly on mechanisms of tissue damage and inflammation. Taken together, these markers can help optimise therapeutic strategies and reduce disease burden. Here, we review the recent advances in the identification of malarial biomarkers, focusing on those related to parasite exposure and disease susceptibility. We also discuss priorities for research in biomarkers for severe malaria.

Soluble Angiogenic Factors in Patients With Acute Pancreatitis

Angiogenic factors are involved in the physiopathology of several inflammatory diseases and they probably play a role in the pathogenesis of acute pancreatitis (AP). To investigate if angiogenic factors are elevated in patients with AP, their relationship with severity and clinical evolution of AP, and their use as prognosis markers of AP. A case (25)-control (30) study was carried out. Patients with AP were classified according to severity (using Ranson and Glasgow scores) and according to their clinical evolution (taking into account the development of complications during hospital stay). Platelet-derived growth factor (PDGFBB), angiopoietin-1, angiopoietin-2 (Ang-2), angiopoietin tyrosine-kinase receptor, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), VEGF tyrosine-kinase receptor 1, and VEGF tyrosine-kinase receptor 2 were determined at 12 hours and then at 5 days after hospitalization. PDGFBB, Ang-2, angiopoietin tyrosine-kinase receptor, and HGF were significantly higher in cases (P<0.001), and in patients with unfavorable clinical evolution (P<0.001). PDGFBB and HGF were significantly higher in patients with severe AP (P<0.05). To predict unfavorable clinical evolution, PDGFBB, Ang-2, and HGF showed an area under receiver operating characteristic curve of 0.97. PDGFBB and HGF are related to severity of AP. These factors along with Ang-2 are related to clinical evolution and are useful in predicting the development of several complications during hospital stay. Therefore, these angiogenic factors could be useful as prognosis markers of AP.