Epilepsy, status epilepticus, and hemiplegic migraine coexisting with a novel SLC4A4 mutation.

BACKGROUND: Recessive mutations in the SLC4A4 gene cause a syndrome characterised by proximal renal tubular acidosis (pRTA), mental retardation, dental and ocular abnormalities, and hemiplegic migraine. Rare cases involving the development of epilepsy or its severe complication-status epilepticus-have been described. METHODS: The clinical and genetic status of four affected members in a Spanish family was studied. The SLC4A4 gene mutation was detected with a next-generation sequencing (NGS) panel in the proband, and Sanger confirmed the putative mutations in affected relatives. In silico analysis was performed to elucidate the putative effect of mutation on the splicing process. RESULTS: A novel mutation, c.2562+2T>G, was identified in the homozygous state in all diseased members of the family. This mutation affected a canonical splice site and is predicted to abolish the wild-type donor site, which predicts a premature truncated NBCe1 protein with cotransport activity. The resulting protein lacks the 190 amino acids of the carboxyl-terminus, and the effect is likely to be a loss of function. All patients suffered from severe pRTA and ocular abnormalities, and the adults also suffered from neurological complications, such as hemiplegic migraine and/or epilepsy. Two developed life-threatening status epilepticus, although they fully recovered and remained free of seizures with valproate. CONCLUSION: These results expand the clinical and mutational spectra of SLC4A4-related disease and have implications for understanding the potential role of NBCe1 in the pathophysiologic processes of hemiplegic migraine and epilepsy/status epilepticus associated with the mutation.

Impact of isolated hepatitis C virus (HCV) core-specific antibody detection and viral RNA amplification among HCV-seronegative dialysis patients at risk for infection.

Amplification of hepatitis C virus (HCV) RNA from blood detected occult HCV infections in 30.9% of 210 HCV-seronegative dialysis patients with abnormal liver enzyme levels that had evaded standard HCV testing practices. Isolated HCV core-specific antibody detection identified three additional anti-HCV screening-negative patients lacking HCV RNA amplification in blood who were considered potentially infectious. Together, these findings may affect management of the dialysis setting.

[OPINION OF HEALTH PROFESSIONALS ON ADHERENCE AND MANAGEMENT OF LONG-TERM TREATMENTS IN ADOLESCENTS]. / Opinión de los profesionales sanitarios sobre a adherencia y manejo de tratamientos de larga duración en adolescents.

OBJECTIVE: To assess opinion of health professionals about adherence and management of long-term treatments in adolescents in a tertiary hospital. METHOD: A cross-sectional study was carried out in the Vall d'Hebron University Hospital in Barcelona, Spain. Participants were health professionals who care adolescents with solid organ transplant, hematologic disease, diabetes, cystic fibrosis or HIV+. Data collection was performed by self-administered questionnaire, developed specifically for this study. RESULTS: A total of 105 professionals (70%) participated in the study, 80% were nurses, 56% of them indicated that treatment compliance was good. 43% indicated that adherence was not addressed well and 79% of professionals did not have planned time to conduct health education related to treatment. 19.5% of nurses and 72.2% of physicians reported having adherence assessment tools. 39% of participants made suggestions for improvement. CONCLUSIONS: Almost half of the professional indicate that the adherence is not adequately addressed. It is important to evaluate adherence to treatment to identify causes of low compliance and establish and evaluate appropriate interventions.

Case report: Efficacy of immunotherapy as conversion therapy in dMMR/MSI-H colorectal cancer: a case series and review of the literature.

Immunotherapy has demonstrated a role in the therapeutic landscape of a small subset of patients with colorectal carcinoma (CRC) that harbor a microsatellite instability (MSI-H) status due to a deficient DNA mismatch repair (dMMR) system. The remarkable responses to immune checkpoint inhibitors (ICIs) are now being tested in the neoadjuvant setting in localized CRC, where the dMMR/MSI-H status can be found in up to 15% of patients, with remarkable results obtained in NICHE2 and 3 trials, among others. This case series aims to report our experience at a tertiary center and provide a comprehensive analysis of the possible questions and challenges to overcome if ICIs were established as standard of care in a neoadjuvant setting, as well as the potential role they may have as conversion therapy not only in locoregional advanced CRC but also in oligometastatic disease.

A multi-country study of intussusception in children under 2 years of age in Latin America: analysis of prospective surveillance data.

BACKGROUND: Intussusception (IS) is a form of acute intestinal obstruction that occurs mainly in infants and is usually of unknown cause. An association between IS and the first licensed rotavirus vaccine, a reassortant-tetravalent, rhesus-based rotavirus vaccine (RRV-TV), led to the withdrawal of the vaccine. New rotavirus vaccines have now been developed and extensively studied for their potential association with IS. This study aimed to describe the epidemiology and to estimate the incidence of IS in Latin American infants prior to new vaccine introduction. METHODS: Children under 2 years of age representing potential IS cases were enrolled in 16 centers in 11 Latin American countries from January 2003 to May 2005. IS cases were classified as definite, probable, possible or suspected as stated on the Brighton Collaboration Working Group guidelines. RESULTS: From 517 potential cases identified, 476 (92%) cases were classified as definite, 21 probable, 10 possible and 10 suspected for intussusception. Among the 476 definite IS cases, the median age at presentation was 6.4 months with 89% of cases aged <1 year. The male to female ratio was 1.5:1. The incidence of definite IS per 100,000 subject-years ranged from 1.9 in Brazil to 62.4 in Argentina for children <2 years of age, and from 3.8 in Brazil to 105.3 in Argentina for children aged <1 year. Median hospital stay was 4 days with a high prevalence of surgery as the primary treatment (65%). Most cases (88%) made a complete recovery, but 13 (3%) died. No clear seasonal pattern of IS cases emerged. CONCLUSIONS: This study describes the epidemiology and estimates the incidence of IS in Latin American infants prior to the introduction of new rotavirus vaccines. The incidence of IS was found to vary between different countries, as observed in previous studies. TRIAL REGISTRATION: Clinical study identifier 999910/204 (SERO-EPI-IS-204).

Six-month safety follow-up of an adjuvanted SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019) in adults: A phase 2/3, double-blind, randomized study.

BACKGROUND: We evaluated the safety of SCB-2019, a protein subunit vaccine candidate containing a recombinant SARS-CoV-2 spike (S) trimer fusion protein, combined with CpG-1018/alum adjuvants. METHODS: This ongoing phase 2/3, double-blind, placebo-controlled, randomized trial is being conducted in Belgium, Brazil, Colombia, the Philippines, and South Africa in participants ≥ 12 years of age. Participants were randomly assigned to receive 2 doses of SCB-2019 or placebo administered intramuscularly 21 days apart. Here, we present the safety results of SCB-2019 over the 6-month period following 2-dose primary vaccination series in all adult participants (≥18 years of age). RESULTS: A total of 30,137 adult participants received at least one dose of study vaccine (n = 15,070) or placebo (n = 15,067) between 24 March 2021 and 01 December 2021. Unsolicited adverse events, medically-attended adverse events, adverse events of special interest, and serious adverse events were reported in similar frequencies in both study arms over the 6-month follow-up period. Vaccine-related SAEs were reported by 4 of 15,070 SCB-2019 recipients (hypersensitivity reactions in two participants, Bell's palsy, and spontaneous abortion) and 2 of 15,067 placebo recipients (COVID-19, pneumonia, and acute respiratory distress syndrome in one participant and spontaneous abortion in the other one). No signs of vaccine-associated enhanced disease were observed. CONCLUSIONS: SCB-2019 administered as a 2-dose series has an acceptable safety profile. No safety concerns were identified during the 6-month follow-up after the primary vaccination. CLINICAL TRIALS REGISTRATION: NCT04672395; EudraCT: 2020-004272-17.

Localized Colonic Small-Cell Carcinoma with Pathological Complete Response after Neoadjuvant Cisplatin and Etoposide: A Case Report.

Extrapulmonary small-cell carcinoma (SCC) is a rare neoplasm that shares certain features with its pulmonary counterpart and occurs predominantly in the gastrointestinal tract (GIT). It is a high-grade and poorly differentiated neuroendocrine tumor, usually diagnosed in advanced stages, with a poor prognosis and few therapeutic options in that setting. This is a case report of a 77-year-old Spanish male patient with localized SCC of the colon, who presented a pathological complete response in the surgical specimen after neoadjuvant chemotherapy with cisplatin and etoposide. To date, 5 years after surgery, the patient remains without evidence of tumor recurrence. As clinical guidelines for the management of this entity are lacking, and therefore its management has not been standardized, an attempt to summarize the current evidence in the literature was made.

Impact after 10-year use of pneumococcal conjugate vaccine in the Brazilian national immunization program: an updated systematic literature review from 2015 to 2020.

In 2010, a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was introduced in the Brazilian national immunization program; the 3 + 1 dose schedule was replaced by a 2 + 1 dose schedule in 2016. This systematic review presents the latest published evidence (2015-2020) on the impact after 10-year use of PHiD-CV in Brazil from a total of 29 publications. Overall, the PHiD-CV program had a positive impact on the morbidity and mortality associated with invasive pneumococcal disease (IPD), pneumonia and acute otitis media (AOM) in children <5 years-old. A reduction in the vaccine-type invasive disease was observed in all-ages; suggesting indirect protection unvaccinated older children and adults. The occurrence of non-vaccine type disease was evidenced in some studies. Higher vaccination coverage is required at national and state level for sustained population impact. Given the change in the vaccination schedule and the dynamics of pneumococcal disease epidemiology, continuous surveillance is warranted.GSK Study identifier: HO-18-19438.

10Vida: A Mental and Physical Health Intervention for Chronically Ill Adolescents and Their Caregivers in the Hospital Setting: An Open Study.

Suffering from a chronic disease (CD) in adolescence can significantly impact the emotional health of adolescents and their families. MHealth can be a useful tool for these groups. However, few intervention programmes include the family system. The aim is to design an intervention programme (10Vida) for a paediatric population with a CD, and their families, to improve their adaptation to the disease. The study is a quasi-experimental repeated measures design in a open study, where the patients themselves, and their families, are their own control group. Participants will receive an intervention of seven individual sessions: five sessions with each patient, and two sessions with their caregivers. In the case of the patients, the aim is to improve their emotional state, their self-esteem, and their emotional competencies, reducing their perceived threat of illness. Furthermore, in the case of the caregivers, the aim is to improve their emotional state and reduce their burden. Indirectly, working with caregivers and those being cared for will improve family ties. The pilot study will involve 25 to 30 chronically ill adolescents aged between 12 and 16 years and their primary caregivers. Following the results, the necessary modifications will be included, and the programme will be offered to adolescents and their families who are willing to participate.

Corneal graft surgery: A monocentric long-term analysis.

PURPOSE: To investigate indications, outcomes and changes in clinical patterns of keratoplasty surgery in a Spanish tertiary eye center. SETTING: Vissum Instituto Oftalmológico, Alicante, Spain. METHODS: A retrospective review was performed on clinical records of patients that underwent any kind of corneal transplant from 2001 to 2017 in the study center. Inclusion criteria involved the presence of detailed preoperative examination, surgical report and at least 12 months follow-up after the surgery. A statistical analysis was performed on the indications for keratoplasty, survival rates, type of graft failures, and visual outcomes. RESULTS: A total of 907 keratoplasties procedures were identified. About 432 penetrating keratoplasty (PK), 148 deep anterior lamellar keratoplasty (DALK), and 134 endothelial keratoplasty (EK) met the inclusion criteria. Cumulative survival rate ranged from 94% to 69% in a 1-year period and from 85% to 45% in a 5-years period according to the different graft types. The main cause for failure was immunological rejection for PK, surface diseases for DALK and primary graft failure for EK. Postoperative visual function improved for all the surgical techniques. CONCLUSION: Corneal transplant is a challenging surgery still complicated by a relevant risk of failure. Our study offers a useful opinion of the current trends on keratoplasty in our country, where the outcomes of the grafts differ considerably in relation to the indications and the different surgical techniques, with lamellar procedures that showed higher rates of success and better visual outcomes than full-thickness grafts.

Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.

BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)

Effect of the seasoning method on the chemical composition of oak heartwood to cooperage.

The effect of various oak wood seasoning methods, natural seasoning in open air, artificial seasoning in a kiln, and a mixed method that combines open air and kiln drying, on the chemical composition in American ( Quercus alba) and French ( Quercus petraea) oak was studied. The results confirm the evolution of ellagitannins in wood, low molecular polyphenols, and volatile compounds in relation to oak species and seasoning method. Natural seasoning in open air can be considered a superior method to mixed or artificial drying for wood seasoning in cooperage. It was more effective in reducing the excess of ellagitannins, especially in French oak wood. Moreover, the evolution of wood volatile compounds was more positive in the natural seasoning than mixed or artificial drying, since it led to woods with higher aromatic potential (larger concentrations of compounds such as volatile phenols, phenolic aldehydes, furanic compounds, and cis- and trans-beta-methyl-gamma-octalactones) than mixed or artificial methods. However, the three seasoning methods showed similar effectiveness regarding the desired reduction of off-flavors compounds.

Hepatitis A as an etiologic agent of acute liver failure in Latin America.

BACKGROUND: This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. METHODS: The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. RESULTS: Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). CONCLUSIONS: HAV was the main etiologic agent of ALF in the population studied.

Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.

OBJECTIVE: To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. METHODS: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE. RESULTS: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. CONCLUSIONS: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

[Homocysteine and progression of carotid atherosclerosis in patients with coronary disease]. / Homocisteína y progresión de la aterosclerosis de la arteria carótida en pacientes con enfermedad coronaria.

BACKGROUND AND OBJECTIVE: Carotid intima-media thickness (IMT) is a marker of generalized atherosclerosis. Sequential evaluation of carotid IMT has permitted to know the factors involved in its progression. However, there are few studies about the influence of homocysteine in such progression. The aim of this work was to know the effect of homocysteine values on the evolution of carotid IMT in patients with coronary disease. PATIENTS AND METHOD: Carotid IMT (baseline and after 4 years of follow-up) was evaluated by a B-mode ultrasonography in 187 patients with coronary disease (166 males and 21 females; age: mean [standard deviation], 60 [7] years); 185 patients were treated with statins from the beginning of the study. RESULTS: Carotid IMT progression was confirmed in 59 patients (31.6%; 95% confidence interval [CI], 25.0-38.7%). Cardiovascular risk factors, basal biochemical parameters and methylenetetrahydrofolate reductase-C677T polymorphism were similar in patients with and without progression except for homocysteine values which were higher in the former (13.3 [5.3]; 95% CI, 12.0-14.6 vs 11.1 [3.5]; 95% CI, 10.5-11.7 (mol/l; p = 0.001). Biochemical changes at the end of the study were similar in both groups. In the multivariate analysis, IMT progression was associated with basal values of homocysteine (odds ratio [OR] 1.19; 95% CI, 1.07-1.31; p = 0.0008), female gender (OR 3.50; 95% CI, 1.17-10.50; p = 0.02), hypertension (OR 2.52; 95% CI, 1.14-5.59; p = 0.02) and basal high-density lipoprotein (HDL)-cholesterol values (OR, 0.94; 95% CI, 0.90-0.98; p = 0.009). CONCLUSIONS: The concentration of homocysteine is associated with the progression of carotid atherosclerosis in patients with coronary heart disease treated with statins.

Reproductive phenology and pre-dispersal fruit predation in Atriplex halimus L. (Chenopodiaceae).

BACKGROUND: The flowering phenology pattern of Atriplex halimus was studied in a Mediterranean habitat in order to analyze protandry effectiveness. Fruit set evolution was recorded over two years and the impact of pre-dispersal predation by insects was also evaluated. RESULTS: The flowering phenology coincided in 2006 and 2007, starting in mid-July and reaching full flowering at the end of August in both years. Inflorescences are composed of glomerules with 8.78 ± 2.79 male flowers and 4.57 ± 2.58 female flowers, with no significant differences in position on the inflorescence. The peaks of male and female flower anthesis were reached in mid-August, but the male maximum occurred one week before the female. Plants at the start of flowering only bear male flowers, but female flowers soon appear. Fruit set starts at the end of August; all the flowers were transformed into fruit by mid-September and their development continued to the beginning of October, when fruit structures had matured and began to drop. Fruit predation started at the end of September and reached maximum intensity in mid-October. CONCLUSIONS: At population level, male and female flowers seemed to open in the same weeks, but at plant and glomerule level male flowers opened one week before the females. Fruit predation levels were 62.42 and 43.14% in 2006 and 2007 respectively, with no significant differences between different parts of the inflorescence. And larvae of Coleophoridae were the most abundant predators.

Sorption of 2,4-d on natural and organic amended soils of different characteristics.

The effect of one organic amendment consisting of an urban waste compost (UWC) was assessed on the sorption properties of the herbicide 2,4-D on four soils of different physicochemical characteristics. The soils chosen were a Typic Haphorthod (ST), a Typic Endoaquept (SR), an Entic Pelloxerert (TO), and a Typic Eutrochrept (AL). Adsorption experiments were performed on the original soils, and on mixtures of these soils with UWC at a rate of 6.25% (w/w). These mixtures were used just after preparation, and after aging for 8 and 25 weeks. 2,4-D adsorption was the highest on ST soil, whereas the lowest adsorption was for SR soil. This behavior is related to the high amount of organic matter (OM) and amorphous iron and aluminum oxides content on soil ST, whereas soil SR had the lowest OM content and specific surface area of the soils of this study. Addition of exogenous OM to soils caused an increase in the 2,4-D adsorption by three of the soils treated with UWC, with the only exception being ST soil, due to an observed decrease in its specific surface area. The adsorbed amounts of the herbicide on aged organic fertilized soils diminished in three of the amended soils, but was still greater than on unammended soils. In contrast, the ST soil showed the largest adsorption for unammended soil.

DTPw-HB and Hib primary and booster vaccination: combined versus separate administration to Latin American children.

This multicentre study was designed to establish the reactogenicity and immunogenicity profiles of primary and booster vaccination with diphtheria, tetanus, and pertussis whole-cell-hepatitis B/Haemophilus influenzae type-b (DTPw-HB/Hib) administered as either a syringe mix or as separate injections in 400 Latin American children. Both vaccine regimens were equally well tolerated and elicited post-primary excellent seropositivity rates at or close to 100% for all five component antigens. With regard to HB, 100% of subjects in the combined vaccination group, and 98.8% subjects in the separate injection vaccination group reached seroprotective antibody concentrations (>or=10 mIU/ml) 1 month after the primary vaccination course. Equally high anti-PRP antibody concentrations were reached 1 month after vaccination, with 100% of seroprotected subjects in the combined vaccination group (antibody concentrations >or=0.15 microg/ml), against 99.4% in the separate injection vaccination group. Seroprotective anti-HBs and anti-PRP antibody concentration levels persisted approximately 1 year after the primary vaccination course, just prior to booster vaccination. Finally, a significant increase of all antibody concentrations could be observed after the booster vaccination, since all but one subject in the separate injection vaccination group had protective levels of anti-HBs and anti-PRP antibodies 1 month after the booster dose. These results suggest that the combination of DTPw-HB and Hib vaccines provides an effective means for increasing vaccine coverage in childhood vaccination programmes.