Hepatitis E: current status

Acute hepatitis E is a very common disease in developing countries, to the point that, according to World Health Organization estimates, one third of the world's population has been exposed to HEV. It also causes outbreaks in refugee camps or after natural disasters such as floods or earthquakes. Sporadic cases of acute hepatitis have been observed in practically all European countries and other developed geographical areas, not only in travelers from endemic countries but also in people with no risk factors. But, lately, new aspects of this infection are appearing in industrialized countries such as the possibility of the disease becoming chronic in transplant patients, the immunocompromised in general, and even in patients with previous liver disease who are immunocompetent. In this comprehensive review, we summarize the current knowledge on HEV infection. Copyright © 2013 John Wiley & Sons, Ltd.     

Impacto de la infección por el nuevo coronavirus en los pacientes con uveítis asociada a una enfermedad autoinmune: resultado de la encuesta COVID-19-GEAS pacientes

IntroductionThe objetive of these study is to know the characteristics of COVID-19 in patients with uveitis associated with Systemic Autoimmune Disease (SAD) through telematic survey.Material and methodsInternal Medicine Society and Group of Systemic Autoimmune disease conducted a telematic survey of patients with SAD to learn about the characteristics of COVID-19 in this population.ResultsA total of 2,789 patients answered the survey, of which 28 had a diagnosis of uveitis associated with SAE. The majority (82%) were female and caucasian (82%), with a mean age of 48 years. The most frequent SAEs were Behçet's disease followed by sarcoidosis and systemic lupus erythematosus. 46% of the patients were receiving corticosteroid treatment at a mean prednisone dose of 11 mg/day. Regarding infection, 14 (50%) patients reported symptoms compatible with SARS-CoV-2 infection. RT-PCR was performed on the nasopharyngeal smear in two patients and in one of them (4%) it was positive.ConclusionsBoth asymptomatic and symptomatic COVID-19 patients with ASD-associated UNI had received similar immunosuppressive treatment.     

GnRH agonist with low-dose hCG (dual trigger) is associated with higher risk of severe ovarian hyperstimulation syndrome compared to GnRH agonist alone

Purpose

The purpose of this study was to compare rates of ovarian hyperstimulation syndrome (OHSS) after using gonadotropin-releasing hormone agonists (GnRHa) alone and GnRHa in combination with low-dose human chorionic gonadotropin (hCG, dual trigger) for final oocyte maturation in women undergoing controlled ovarian hyperstimulation (COH).

Methods

A retrospective cohort study was conducted at an academic center. Study population included 108 women who received GnRHa trigger and 66 women who received dual trigger (GnRHa?+?low-dose [1000 IU] hCG trigger). The main outcome measure was OHSS. Secondary outcomes included total oocyte yield and oocyte maturity.

Results

The incidence of early OHSS was significantly higher after dual trigger than GnRHa trigger (8.6 vs 0 %). Moreover, four of the six patients that developed OHSS developed severe OHSS. Logistic modeling revealed that the combination of age, BMI, baseline AFC, and E2 >4000 pg/mL was predictive of OHSS with an area under the receiver operating characteristic curve of 0.84 and was superior to each factor alone. Adjusted analyses revealed that dual trigger was associated with a higher number of total oocytes (adjusted OR 1.27; 95 % confidence interval, 1.18, 1.38) and percentage of mature oocytes (AOR 1.10; 95 % confidence interval, 1.03, 1.17) obtained compared to GnRHa trigger alone.

Conclusions

Dual trigger for final oocyte maturation using GnRHa and low-dose hCG is associated with a significantly increased risk of severe OHSS compared to GnRH alone. However, dual trigger may be associated with a modest increase in oocyte yield, both in terms of number and maturity.

     

Risk factors for congenital diaphragmatic hernia in the Bogota birth defects surveillance and follow-up program,Colombia

Purpose

The mortality rate for congenital diaphragmatic hernia (CDH) remains high and prevention efforts are limited by the lack of known risk factors. The aim of this study was to determine prevalence, risk factors, and neonatal results associated with CDH on a surveillance system hospital-based in Bogotá, Colombia.

Methods

The data used in this study were obtained from The Bogota Birth Defects Surveillance and Follow-up Program (BBDSFP), between January 2001 and December 2013. With 386,419 births, there were 81 cases of CDH. A case–control methodology was conducted with 48 of the total cases of CDH and 192 controls for association analysis.

Results

The prevalence of CDH was 2.1 per 10,000 births. In the case–control analysis, risk factors found were maternal age ≥35 years (OR, 33.53; 95 % CI, 7.02–160.11), infants with CDH were more likely to be born before 37 weeks of gestation (OR, 5.57; 95 % CI, 2.05–15.14), to weigh less than 2500 g at birth (OR, 9.05; 95 % CI, 3.51–23.32), and be small for gestational age (OR, 5.72; 95 % CI, 2.18–14.99) with a high rate of death before hospital discharge in the CDH population (CDH: 38 % vs BBDSFP: <1 %; p < 0.001).

Conclusions

The prevalence of CDH calculated was similar to the one reported in the literature. CDH is strongly associated with a high rate of death before hospital discharge and the risk factors found were maternal age ≥35 years, preterm birth, be small for gestational age, and have low weight at birth. These neonatal characteristics in developing countries would help to identify early CDH. Prevention efforts have been limited by the lack of known risk factors and established epidemiological profiles, especially in developing countries.

     

The Effect of High‐Mobility Group Box 1 in Rat Steatotic and Nonsteatotic Liver Transplantation From Donors After Brain Death

High‐mobility group box 1 (HMGB1) has been described in different inflammatory disorders, and the deleterious effects of brain death (BD) may counteract the protection conferred by ischemic preconditioning (IP), the only surgical strategy that is being applied in clinical liver transplantation. Our study examined how HMGB1 may affect preconditioned and unpreconditioned steatotic and nonsteatotic liver grafts from donors after BD (DBDs) for transplantation. HMGB1 was pharmacologically modulated in liver grafts from DBDs, and HMGB1‐underlying mechanisms were characterized. We found that BD decreased HMGB1 in preconditioned and unpreconditioned livers and was associated with inflammation and damage. Exogenous HMGB1 in DBDs activates phosphoinositide‐3‐kinase and Akt and reduces hepatic inflammation and damage, increasing the survival of recipients. Combination of IP and exogenous HMGB1 shows additional benefits compared with HMGB1 alone. This study provides new mechanistic insights into the pathophysiology of BD‐derived liver graft damage and contributes to the development of novel and efficient strategies to ultimately improve liver graft quality.     

Timing of CMV‐specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation

The aim of this study was to characterize timing, kinetic, and magnitude of CMV‐specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV‐specific T‐cell response was measured in blood, while CMV viral load and chimerism were determined by real‐time PCR. Patients that reconstituted CMV‐specific T‐cell response within 6 weeks after Allo‐SCT showed a more robust immune response (CD8⁺: 0.7 cells/μl vs. 0.3/μl; P‐value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P‐value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P‐value = 0.04), and better overall survival (72%; CI: 0.53–0.96 vs. 42% CI: 0.24–0.71; P‐value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant‐related mortality than nonviremic patients after 1 year (33% CI: 0.15–0.52 vs. 0% CI: 0.05–0.34; P‐value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV‐positive serostatus (P‐value = 0.02) and acquiring CMV‐specific T‐cell response after 6 weeks post‐transplantation (P‐value = 0.009). In conclusion, timing of acquiring a positive CMV‐specific T‐cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.     

A missense mutation in the chloride/proton ClC-5 antiporter gene results in increased expression of an alternative mRNA form that lacks exons 10 and 11. Identification of seven new CLCN5 mutations in patients with Dent’s disease

Mutations in the voltage-gated chloride/proton antiporter ClC-5 gene, CLCN5, are associated with Dent’s disease, an X-linked renal tubulopathy. Our interest is to identify and characterize disease-causing CLCN5 mutations, especially those that alter the splicing of the pre-mRNA. We analyzed the CLCN5 gene from nine unrelated Spanish Dent’s disease patients and their relatives by DNA sequencing. Pre-mRNA splicing analysis was performed by RT-PCR. Seven new mutations were identified, consisting of three missense mutations (C219R, F273L, and W547G), one splice-site mutation (IVS-2A > G), one deletion (976delG), and two non-sense mutations (Y140X and W314X). We found that missense mutation W547G also led to increased expression of a new alternative isoform lacking exons 10 and 11 that was expressed in several human tissues. In addition, we describe another novel CLCN5 splicing variant lacking exon 11 alone, which was expressed only in human skeletal muscle. We conclude that missense mutation W547G can also alter the expression levels of a CLCN5 mRNA splicing variant. This type of mutation has not been previously described in the CLCN5 gene. Our results support the importance of a routine analysis at the pre-mRNA level of mutations that are commonly assumed to cause single amino acids alterations.     

Fibrinolytic therapy in spontaneous intraventricular haemorrhage: efficacy and safety of the treatment

Intraventricular haemorrhage (IVH) is associated with a poor outcome. Simple external ventricular drainage has not modified the high morbidity and mortality of these patients. Our objective was to review our experience using intraventricular urokinase (UK) in treating patients with moderate to severe IVH. Prospective analysis of medical records of 14 patients diagnosed with spontaneous IVH who received ventriculostomy and intraventricular infusion of UK from January 2002 to December 2005. Patients with the following characteristics were included: 18-70 years of age, GCS between 5 and 14, and moderate to severe IVH (Graeb > or = 6) without simultaneous intraparenchymal haematoma > 30 ml. The final results were compared to historic control group (14 patients) treated between January 1999 to December 2001 with ventriculostomy alone. All 28 patients accomplished the inclusion criteria. Patient age, initial GCS and Graeb classification of IVH were similar in the two groups of treatment. There was higher ventriculostomy obstruction rate in the non-UK group (33.3 vs. 0%; p > 0.05), a higher rate of intracranial hypertension in the non-UK group (66.6 vs. 16.6%; p = 0.036) and a lower mortality rate in the UK group (25 vs. 58.3%, p > 0.05). There was no rebleeding associated with UK treatment. Intraventricular UK appears to be a safe treatment. It is effective in the prevention of catheter blockage, speeding the clearance of IVH, and it is associated with lower rate of intracranial hypertension and death.