Pediatric transplantation in Europe during the COVID-19 pandemic: Early impact on activity and healthcare

The current pandemic SARS-CoV-2 has required an unusual allocation of resources that can negatively impact chronically ill patients and high-complexity procedures. Across the European Reference Network on Pediatric Transplantation (ERN TransplantChild), we conducted a survey to investigate the impact of the COVID-19 outbreak on pediatric transplant activity and healthcare practices in both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). The replies of 30 professionals from 18 centers in Europe were collected. Twelve of 18 centers (67%) showed a reduction in their usual transplant activity. Additionally, outpatient visits have been modified and restricted to selected ones, and the use of telemedicine tools has increased. Additionally, a total of 14 COVID-19 pediatric transplanted patients were identified at the time of the survey, including eight transplant recipients and six candidates for transplantation. Only two moderate-severe cases were reported, both in HSCT setting. These survey results demonstrate the limitations in healthcare resources for pediatric transplantation patients during early stages of this pandemic. COVID-19 disease is a major worldwide challenge for the field of pediatric transplantation, where there will be a need for systematic data collection, encouraging regular discussions to address the long-term consequences for pediatric transplantation candidates, recipients, and their families.     

Severe hyperglycemia: a determinant factor for hypofiltration in alloxan diabetic rats

Abstract. The relationships among glomerular filtration rate, renal plasma flow and extracellular fluid volume were investigated in control and severely hyperglycemic (442±33 mg/dl) untreated, alloxan diabetc rats. Most of diabetic animals showed significant lower values of inulin clearance (diabetics, 0.55±0.07 ml/min·100 g; controls, 0.97±0.04) and p-aminohippurate clearance (diabetics, 2.11±0.39 ml/min·100 g; controls, 3.93±0.25). Diabetic rats exhibited reduced efficiency in tubular Na⁺ reabsorption, increased urinary Na⁺ excretion (diabetics, 3.12±0.27 mEq/day; controls, 1.25±0.14) and diminished values of plasma renin activity (diabetics, 3.34±0.44 ng/ml·h; controls, 8.64±0.79). Significant negative correlations were found between glycemia and renal hemodynamic variables. Acute overload with glucose further decreased these variables in both groups: inulin clearance in diabetics vs. controls, 0.26±0.04 vs. 0.44±0.05 ml/min·100 g; p-aminohippuric acid clearance in diabetics vs. controls, 1.09±0.20 vs. 1.55±0.21 ml/min·100 g. We conclude that chronically hyperglycemic alloxan diabetic rats showed diminished glomerular filtration rates (inulin clearance), renal plasma flow (p-aminohippurate clearance) and extracellular fluid volume associated with urinary Na⁺ losses and alterations in the renin-angiotensin system. Decreased reninangiotensin system activity might reduce aldosterone secretion, which in turn could result in (succesively) urinary sodium loss, extracellular fluid volume contraction and reductions in glomerular filtration and renal plasma flow.     

Observational study of optimization of biologic therapies in rheumatoid arthritis: a single-centre experience

To analyse the effectiveness of optimization of biologics in rheumatoid arthritis (RA). It was a single-centre retrospective observational study from January 2009 to September 2012. The effectiveness of the optimization of TNF antagonists, tocilizumab and abatacept in RA was studied. Optimization included predefined dose down-titration and/or expansion of dose interval in early arthritis with sustained DAS28-ESR <2.6 and established arthritis with a sustained DAS28-ESR <3.2. Primary outcome was time to relapse defined as increase in DAS28-ESR greater than 20 % over baseline. Cox’s regression analysis was performed to identify predictors of relapse. Sixty-four patients were included in the study. In the survival analysis, rates of relapse were 9.8 % at 6 months, 31.4 % at 12 months and 44.6 % at 18 months. Rates of patients with an increase in DAS28-ESR > 20 % and ≥1 inflamed joint at 6, 9 and 18 months were 1.6, 17.2 and 27.1 %, respectively. In relapsing patients, mean DAS28-ESR at relapse was 3.44 (2.94–4.79) and mean DAS28-ESR following the return to the prior dose of the biologic was 2.52 (1.42–3.21). No predictors of relapse were found in multivariate analysis. Optimization of the treatment with biologics in RA is an efficacious and safe treatment option.     

Rare cause of abdominal incidentaloma: Hepatoduodenal ligament teratoma

The occurrence of a hepatoduodenal ligament teratoma is extremely rare,with only a few cases reported in the literature.This case report describes the discovery of a hepatoduodenal ligament lesion revealed during abdominal ultrasonography for cholelithiasis-related abdominal pain in a 27-year-old female.Cross-sectional imaging identified a 5 cm×4 cm heterogeneous mass of fat tissue with irregular calcification located in the posterior-superior aspect of the head of the pancreas.An encapsulated lesion showing no invasion to the common bile duct or adjacent organs and vessels was exposed during laparotomy and resected.Intraop-erative cholangiography during the cholecystectomy showed no abnormalities.The postoperative course was uneventful.Pathological analysis of the resected mass indicated hepatoduodenal ligament teratoma.This case report demonstrates that cross-sectional im-aging,such as computed tomography,can reveal sus-pected incidences of this rare type of teratoma,which can then be confirmed after pathologic analysis of the specimen.The prognosis after complete surgical resec-tion of lesions presenting with benign pathological fea-tures is excellent.     

Chronic pelvic pain syndrome: Highlighting medicinal plants toward biomolecules discovery for upcoming drugs formulation

Chronic pelvic pain syndrome (CPPS) can be triggered by a various types of gynecological, gastrointestinal, urological, and musculoskeletal disorders. Recently, the role of the central nervous system has proven to be an integral part on the development of any chronic pain syndrome, including CPPS. However, owing to the complex and heterogeneous etiology and pathophysiology of CPPS, the establishment of effective therapeutic interventions remains challenging for both physicians and patients. Nonetheless, recent studies have pointed that medicinal plants and their secondary metabolites can be effectively used in CPPS therapy, besides contributing to restore the patients' quality of life and potentiate the conventional CPPS management. In this sense, this review aims to provide a careful overview on the biomedical data for the use of medicinal plants use and their secondary metabolites on CPPS management.     

Apigenin as an anticancer agent

Apigenin is an edible plant‐derived flavonoid that has been reported as an anticancer agent in several experimental and biological studies. It exhibits cell growth arrest and apoptosis in different types of tumors such as breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach, by modulating several signaling pathways. Apigenin induces apoptosis by the activation of extrinsic caspase‐dependent pathway by upregulating the mRNA expressions of caspase‐3, caspase‐8, and TNF‐α. It induces intrinsic apoptosis pathway as evidenced by the induction of cytochrome c, Bax, and caspase‐3, while caspase‐8, TNF‐α, and B‐cell lymphoma 2 levels remained unchanged in human prostate cancer PC‐3 cells. Apigenin treatment leads to significant downregulation of matrix metallopeptidases‐2, ?9, Snail, and Slug, suppressing invasion. The expressions of NF‐κB p105/p50, PI3K, Akt, and the phosphorylation of p‐Akt decreases after treatment with apigenin. However, apigenin‐mediated treatment significantly reduces pluripotency marker Oct3/4 protein expression which might be associated with the downregulation of PI3K/Akt/NF‐κB signaling.     

Omega-3 Fatty Acid Intake during Pregnancy and Child Neuropsychological Development: A Multi-Centre Population-Based Birth Cohort Study in Spain

Background: There are few studies that look at the intake of all types of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during the different stages of pregnancy along with a long-term neuropsychological follow-up of the child. This study aims to explore the association between maternal n-3 PUFA intake during two periods of pregnancy and the child’s neuropsychological scores at different ages. Methods: Prospective data were obtained for 2644 pregnant women recruited between 2004 and 2008 in population-based birth cohorts in Spain. Maternal n-3 PUFA intake during the first and third trimester of pregnancy was estimated using validated food frequency questionnaires. Child neuropsychological functions were assessed using Bayley Scales of Infant Development version one (BSID) at 1 year old, the McCarthy Scale of Children’s Abilities (MSCA) at 4 years old, and the Attention Network Test (ANT) at 7 years old. Data were analysed using multivariate linear regression models and adjusted for potential covariates, such as maternal social class, education, cohort location, alcohol consumption, smoking, breastfeeding duration, and energy intake. Results: Compared to participants in the lowest quartile (<1.262 g/day) of n-3 PUFA consumption during the first trimester, those in the highest quartile (>1.657 g/day) had a 2.26 points (95% confidence interval (CI): 0.41, 4.11) higher MSCA general cognitive score, a 2.48 points (95% CI: 0.53, 4.43) higher MSCA verbal score, and a 2.06 points (95% CI: 0.166, 3.95) higher MSCA executive function score, and a 11.52 milliseconds (95% CI: −22.95, −0.09) lower ANT hit reaction time standard error. In the third pregnancy trimester, the associations were weaker. Conclusions: Positive associations between n-3 PUFA intake during early pregnancy and child neuropsychological functions at 4 and 7 years of age were found, and further clinical research is needed to confirm these findings.     

Novel genetic markers of rheumatoid arthritis in chilean patients,by dr serotyping and restriction fragment length polymorphism analysis

Objective. The analysis of genetic markers of rheumatoid arthritis (RA) in a population in which the DR4 serotype is not strongly associated with the disease. Methods. Chilean RA patients (56 seropositive and 22 seronegative) and 141 controls were studied by serotyping. Southern blot analysis of Bam HI restriction fragment length polymorphism (RFLP) was done in genomic DNA from 46 patients with seropositive RA, 17 patients with seronegative RA, and 45 controls, using a complementary DNA probe specific for DRB1 genes. Results. The prevalence of the HLA—DR9 haplotype was strikingly higher in seropositive RA patients (21%) than in controls (3%) (P_corr < 0.0008, by Fisher's exact test; relative risk [RR] = 9.34). The prevalence of DR4 and DR1 haplotypes, although slightly increased, did not achieve a significant preponderance. The simultaneous presence of two Bam HI fragments (3.6 kb and 4.5 kb) was found with higher prevalence in seropositive patients (83%; RR = 9; P_corr < 0.00002) than in controls (36%), and seemed higher in seronegative RA patients as well (71%; RR = 4). Furthermore, its prevalence remained increased in comparisons of DR4 positive controls (36%) with DR4 positive seropositive patients (100%; RR = 67; P_corr < 0.0002) and DR4 positive seronegative patients (100%; RR = 36; P_corr < 0.006), even after excluding the DR9 positive individuals. A tendency toward higher association with DR1 seropositive RA patients (67%; RR = 12), a group with no DR4 or DR9 positive individuals, than in DR1 positive controls (14%), was also observed. Conclusion. The HLA—DR9 haplotype was definitively consolidated as a very strong genetic marker exclusively for seropositive RA in Chilean patients, as suggested by our previous observations. RFLP analysis showed that the simultaneous presence of 3.6-kb and 4.5-kb Bam HI fragments constituted a better RA marker than did any of the heretofore studied haplotypes. These fragments together would be linked to RA independently of the DR1, DR4, and DR9 haplotypes. The overall evidence indicates that Chilean seropositive RA patients display a genetic background that is different from that underlying RA susceptibility in other populations and suggests the existence of common, as well as distinct, genetic elements predisposing to seronegative and seropositive RA.     

The Application of Beta-Tricalcium Phosphate in Implant Dentistry: A Systematic Evaluation of Clinical Studies

The demand for synthetic graft materials in implant dentistry is rising. This systematic review aims to evaluate the survival rate of dental implants placed simultaneously with bone regeneration procedures using the material β-tricalcium phosphate, one of the most promising synthetic graft materials. The electronic search was conducted in PubMed, Scielo, and the Cochrane Central Register of Controlled Trials. Five randomized clinical trials, one non-randomized controlled clinical trial and four observational studies without control group were include. Implant survival rate and other clinical, radiographic, and histological parameters did not differ from those of implants placed simultaneously with another type of graft material, or placed in blood clots or natural alveolar ridges. Based on the available literature, β-tricalcium phosphate seems to be a promising graft material in implant dentistry. Nevertheless, more randomized clinical trials, with long follow-up periods, preoperative and postoperative CBCT, and histological analysis, are necessary to assess its long-term behavior.     

El síndrome de apnea del sueño,la ventilación mecánica y los cuidados críticos en archivos de bronconeumología (diciembre 2009-diciembre 2010)

The present study aims to review all the major articles on respiratory sleep disorders, mechanical ventilation, and respiratory critical care published in the last year in Archivos de bronconeumología. Between December 2009 and November 2010, 15 studies on these topics were published in Archivos de bronconeumología. Ten of these studies dealt with respiratory sleep disorders, consisting of six original articles, one special article, one review article, one letter to the editor and one supplement on chronic obstructive pulmonary disease and its association with sleep apneas. Five articles were published on non-invasive mechanical ventilation: one editorial, one special article, one article in a supplement and two original articles. As in previous years, there was a marked difference in the number of articles published on non-invasive mechanical ventilation and sleep-apnea syndrome, with a greater number of articles being published on the latter. Although some articles highlight the importance of the place where ventilation is commenced, no study specifically dealing with intermediate care units was published in Archivos de bronconeumología in 2010. This absence could be interpreted as a result of the low implantation of this type of unit in Spain, contrasting with the high activity undertaken in this field by pneumology services.