Immunological features in pediatric patients with recurrent and severe infection: Identification of Primary Immunodeficiency Diseases in Merida, Venezuela.

INTRODUCTION AND OBJECTIVES: Primary immunodeficiency diseases (PIDs) are disorders associated mainly with recurrent and severe infection and an increase in susceptibility to autoimmune conditions and cancer. In Venezuela, PIDs are underdiagnosed and there is usually a delay in their diagnosis. Hence there are no data concerning the frequency and type of PIDs that occur. The aim of this study was to identify and quantify the types of PIDs that occur in Merida, a population within Venezuela. PATIENTS OR MATERIALS AND METHODS: Following an informative program designed to alert local health professionals to the warning signs for PIDs, patients with a history of recurrent infections were referred to the Instituto de Inmunologia Clinica, Universidad de Los Andes. RESULTS AND CONCLUSIONS: During the three-year period January 2014 to January 2017, thirty-two cases of PIDs were identified in pediatric patients, and 17 different types of PIDs, were identified. Predominantly antibody deficiencies were most frequent (40.6%), followed by immunodeficiencies affecting cellular and humoral immunity (21.8%), congenital defects of phagocyte (18.7%), CID with associated or syndromic features (9.3%), defects in intrinsic and innate immunity (6.4%) and diseases of immune dysregulation (3.2%). These results have important implications not only to the future approach for management of patients in our regions, but add important knowledge concerning PIDs in Latin America and worldwide.

T-cell profiles elicited by Toxoplasma gondii in acutely/chronically infected humans.

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that can infect almost all warm-blooded species and induce a chronic infection in human hosts. The aim of this work was to investigate Th1, Th2, Th17 and Treg polarization, induced by four important T. gondii antigens (SAG1, ROP1, GRA8 and MAG1) in acutely and chronically infected patients. For this purpose, SAG1, ROP1, GRA8 and MAG1 were expressed as recombinant proteins, purified, and used to evaluate the proinflammatory and regulatory immune response profiles in seropositive and seronegative individuals. Our results show that SAG1 and ROP1 elicited a proinflammatory profile (INF-γ, IL-12 and IL-17) in individuals in the acute phase, whereas MAG1 and GRA8 induced a regulatory pattern (Treg and TGF-ß) in chronically infected patients. These results reveal fundamental differences in T-cell polarization induced by T. gondii antigens, which could have important implications in the immunopathogenesis of the disease and in future proposals of therapeutic strategies.

Saturation mapping of regions determining resistance to Ascochyta blight and broomrape in faba bean using transcriptome-based SNP genotyping.

KEY MESSAGE: Transcriptome-based SNP markers were genotyped in a faba bean map to saturate regions bearing QTL for Ascochyta fabae and broomrape and distinguish positional and functional candidates underlying both resistances. Faba bean is an important food crop worldwide. Marker-assisted selection for disease resistance is a top priority in current faba bean research programs, with pathogens such as Ascochyta fabae and broomrape (Orobanche crenata) being among the major constraints in global faba bean production. However, progress in genetics and genomics in this species has lagged behind that of other grain legumes. Although genetic maps are available, most markers are not in or are too distant from target genes to enable an accurate prediction of the desired phenotypes. In this study, a set of SNP markers located in gene coding regions was selected using transcriptomic data. Ninety-two new SNP markers were genotyped to obtain the most complete map reported so far in the 29H × Vf136 faba bean population. Most of the QTL regions previously described in this cross were enriched with SNP markers. Two QTLs for O. crenata resistance (Oc7 and Oc8) were confirmed. Oc7 and Oc10 located nearby a QTL for A. fabae resistance suggested that these genomic regions might encode common resistance mechanisms and could be targets for selection strategies against both pathogens. We also confirmed three regions in chromosomes II (Af2), III (Af3) and VI associated with Ascochyta blight resistance. The QTLs ratified in the present study are now flanked by or include reliable SNP markers in their intervals. This new information provides a valuable starting point in the search for relevant positional and functional candidates underlying both types of resistance.

Quantitative PCR: an alternative approach to detect common copy number alterations in multiple myeloma.

Chromosome 1q gains and 13q deletions are common cytogenetic aberrations in multiple myeloma (MM) that confer a poor prognosis. There are several techniques for the targeted study of these alterations, but interphase fluorescence in situ hybridization (FISH) is the current gold standard. The aim of the present study was to validate quantitative PCR (qPCR) as an alternative to FISH studies in CD138+-enriched plasma cells (PCs) from MM patients at diagnosis. We analyzed 1q gains and 13q deletions by qPCR in 57 and 60 MM patients, respectively. qPCR applicability was 84 and 88% for 1q and 13q, respectively. The qPCR and FISH methods had a sensitivity and specificity of 88 and 71% for 1q gains, and 79 and 100% for 13q deletions. A second qPCR assay for each region was carried out to confirm the previous results. Paired qPCR (two assays) and FISH results were available from 53 MM patients: 26 for 1q amplification and 27 for 13q deletion. qPCR assays gave concordant results (qPCR-consistent) in 20 of the 26 (77%) 1q gains and 25 of the 27 (93%) 13q deletions. Considering only the consistent data, the overall concordance among qPCR and FISH was 85 and 100% for 1q gains and 13q deletions, respectively. Our results show a substantial agreement between qPCR and the gold standard FISH technique, indicating the potential of qPCR as an alternative approach, particularly when the starting material is too scarce or cells are too damaged to obtain accurate results from FISH studies.

Autologous stem cell transplantation (ASCT) in patients with mantle cell lymphoma: a retrospective study of the Spanish lymphoma group (GELTAMO).

Guidelines recommend autologous stem cell transplantation (ASCT) consolidation in first complete or partial response after regimens including rituximab (R) and high-dose AraC (HDAC), but its use beyond that response is questioned. We present a retrospective analysis of 268 patients with MCL who received ASCT. With a median follow-up for survival patients of 54 months, progression-free survival and overall survival for the whole series were 38 and 74 months, respectively, and for patients transplanted in first CR 49 and 97 months, respectively. Patients without CR before transplant were analyzed separately, those who achieved CR after transplantation had better PFS (48 vs 0.03 months, p < 0.001) and OS (92 vs 16 months, p < 0.001) than the remaining. In univariate analysis, first CR at transplant (p = 0.01) and prior rituximab (p = 0.02) were the variables associated with PFS. For OS, the same variables resulted significant (p = 0.03 and p < 0.001, respectively). In multivariate analysis, only the status at transplant (first CR) remained significant. This retrospective study concludes that ASCT consolidation in first CR induces high survival rates. In other stages of disease, the need of ASCT as consolidation may be questioned.

The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

School-based individualised lifestyle intervention decreases obesity and the metabolic syndrome in Mexican children.

BACKGROUND: Currently, there is limited evidence about effective strategies to manage childhood obesity and the metabolic syndrome in school settings. The present study aims to analyse changes in the prevalence of being overweight/obese and having the metabolic syndrome in relation to a 10-month lifestyle intervention based on individualised face-to-face sessions and parental education in school settings. METHODS: The study sample comprised a cross-sectional sample of 96 overweight/obese Mexican children aged 6-12 years from eight schools. Clinical, anthropometric measurements and 24-h recalls were obtained during each of 13 visits. Laboratory measurements were determined at the beginning and end. The energy-reduced diet was based on dietary recommended intakes. Individualised structured daily meals and a physical activity plan, tailored-made for each child, were provided every 3 weeks at the schools. Parental attendance was required. Student's t-test, McNemar and Shapiro-Wilk tests and simple linear regression were used for the statistical analysis. RESULTS: The prevalence of metabolic syndrome fell significantly from 44% to 16% (P < 0.01), high blood pressure fell from 19% to 0%, hypertrigliceridaemia fell from 64% to 35%, high-density lipoprotein-cholesterol ≤ 40 fell from 60% to 41%, hyperglycaemia fell from 1% to 0%, and waist circumference ≥90th percentile fell from 72% to 57%. There was a 2.84 [95% confidence interval (CI) = -4.10 to -1.58; P < 0.01] significant decrease in body mass index percentile and in body-fat percentage (95% CI = -3.31 to -1.55; P < 0.01). Of the overweight children, 32% achieved normal-weight, whereas 24% of the obese ones converted to overweight and 1% reached normal-weight. Physical activity increased 16 min/day(-1) (P = 0.02) and 2 days/week(-1) . CONCLUSIONS: A school-setting lifestyle intervention led to a decreased prevalence of being overweight/obese and to a striking reduction in the prevalence of the metabolic syndrome in a sample of Mexican children.

Efficacy of mouth rinses and toothpaste on tooth whitening.

OBJECTIVES: People increasingly desire tooth whitening. Considering the wide range of whitening products on the market, this study evaluated the efficacy of whitening toothpastes and mouth rinses compared with the 10% carbamide peroxide (CP) whitening gel. METHODS: We obtained 120 cylindrical specimens from bovine teeth, which were darkened for 24 hours in a coffee solution. The color measurement was performed by a spectrophotometer using the CIE L*a*b* system, and specimens were divided into six groups according to the use of the following agents: group 1, conventional fluoridated toothpaste; group 2, Close Up White Now; group 3, Listerine Whitening; group 4, Colgate Plax Whitening; group 5, experimental mouth rinse with Plasdone; and group 6, 10% CP Whiteness Perfect. After the simulation of 12 weeks of treatment for groups 1 to 5 and 14 days of treatment for group 6, the specimens were subjected to a new color reading. RESULTS: Data were subjected to one-way analysis of variance (α=0.05), which showed significant differences among groups after 12 weeks for ΔE (p=0.001). Results of the Tukey test revealed that groups 3, 4, and 6 presented significantly higher color alteration than groups 1, 2, and 5. CONCLUSIONS: The whitening toothpaste Close Up White Now and the experimental mouth rinse with Plasdone showed similar color alteration as conventional toothpaste after a 12-week treatment simulation. These groups presented significantly lower color alteration compared with whitening mouth rinses Listerine and Colgate Plax Whitening, which showed similar results to those observed after 14 days of bleaching with 10% CP treatment.

[Diaphyseal osteoporotic nonunion of the humerus in elderly patients. Surgical treatment and long-term results]. / No-consolidación diafisaria de húmero en pacientes adultos con osteoporosis. Tratamiento quirúrgico y resultados a largo plazo.

INTRODUCTION: to evaluate the long term radiographic and functional results achieved in adult patients with osteoporotic, atrophic, non-unions of the diaphyseal humerus, treated surgically by open reduction and internal fixation with plates and bone graft. MATERIAL AND METHODS: we retrospectively evaluated 22 patients. Patient's age averaged 72 years. Time from initial trauma to definitive surgery averaged 18 months. Eleven patients were smokers, and four had active infection. Pre-operative Constant score and DASH score averaged 23.13 and 81.04, respectively. Pre-operative pain scale averaged 7.45 points. RESULTS: follow-up averaged 69 months. Union was achieved in all cases after an average of 4.68 months. DASH score at last follow-up averaged 20.27 points and Constant score 79.31 points. Analog pain scale averaged 0.77 points. Stabilization was performed using locking blade plates in 12 non-unions, locking compression plates in six cases, and double plating in four non-unions. Patients with active infection were treated in two stages using Masquelet's technique. Bone graft was associated in all cases (cancellous iliac crest autograft in 17, allograft in three, and combined structural allograft and cancellous autograft in two). Two grams of vancomycin powder were associated to the bone graft in all cases. CONCLUSION: the use of open reduction and internal fixation with plates associated to bone graft with local antibiotics, aloud achieving bony union and good predictable long-term objective and subjective functional results in all cases, without major complications or the need of further surgical intervention.

INTRODUCCIÓN: evaluar los resultados radiográficos y funcionales obtenidos a largo plazo en pacientes adultos que presentaron no-consolidaciones atróficas diafisarias de húmero asociadas a osteoporosis; tratadas quirúrgicamente mediante reducción abierta y fijación interna con placas e injerto óseo. MATERIAL Y MÉTODOS: evaluamos retrospectivamente 22 pacientes, con edad promedio de 72 años, el tiempo desde el trauma inicial hasta la cirugía definitiva promedió, 18 meses. Once pacientes eran fumadores y cuatro presentaban infección activa. El score de Constant y el DASH preoperatorios promediaron 23.13 y 81.04, respectivamente. El valor de la escala analógica del dolor preoperatorio promedió 7.45 puntos. RESULTADOS: el seguimiento promedió 69 meses. Se obtuvo la consolidación en todos los casos, luego de un promedio de 4.68 meses. Al último seguimiento, los valores del DASH promediaron 20.27 puntos y el score de Constant promedió 79.31 puntos. La escala analógica del dolor promedió 0.77 puntos. La estabilización se realizó utilizando clavos placa bloqueados en 12 no-consolidaciones, placas bloqueadas de compresión en seis y doble placa en cuatro. Los pacientes con infección activa fueron tratados en dos etapas utilizando la técnica descripta por Masquelet. Se asoció injerto óseo en todas las reconstrucciones (autoinjerto esponjoso de cresta ilíaca en 17, aloinjerto en tres y se combinó aloinjerto estructural con autoinjerto esponjoso en dos). Dos gramos de vancomicina en polvo fueron asociados localmente al injerto óseo. CONCLUSIÓN: la combinación de reducción abierta y fijación interna con placas e injerto óseo permitió obtener la consolidación y resultados funcionales objetivos y subjetivos buenos y predecibles a largo plazo en todos los casos, sin complicaciones mayores ni la necesidad de intervenciones quirúrgicas sucesivas.

Optical characterization of high performance mirrors based on cavity ringdown time measurements with 6 degrees of freedom mirror positioning.

An instrument capable of measuring optical losses, transmission, and the radius of curvature of high reflectivity mirrors is presented. The measurement setup consists of two remote controlled hexapod systems with 6 degrees of freedom placed inside a vacuum enclosure. Mirror loss measurements are performed via the cavity ring-down time method using a linear resonant two-mirror Fabry-Perot cavity configuration. The use of high-precision positioning systems enables cavity loss mapping by transversely scanning the position of the cavity end mirror. Mirror surfaces of up to 30 mm in diameter can be scanned, and the cavity length can be tuned by 120 mm.

Identification of a novel recurrent gain on 20q13 in chronic lymphocytic leukemia by array CGH and gene expression profiling.

BACKGROUND: The presence of genetic changes is a hallmark of chronic lymphocytic leukemia (CLL). The most common cytogenetic abnormalities with independent prognostic significance in CLL are 13q14, ATM and TP53 deletions and trisomy 12. However, CLL displays a great genetic and biological heterogeneity. The aim of this study was to analyze the genomic imbalances in CLL cytogenetic subsets from both genomic and gene expression perspectives to identify new recurrent alterations. PATIENTS AND METHODS: The genomic imbalances and expression levels of 67 patients were analyzed. The novel recurrent abnormalities detected with bacterial artificial chromosome array were confirmed by FISH and oligonucleotide microarrays. In all cases, gene expression profiling was assessed. RESULTS: Copy number alterations were identified in 75% of cases. Overall, the results confirmed FISH studies for the regions frequently involved in CLL and also defined a new recurrent gain on chromosome 20q13.12, in 19% (13/67) of the CLL patients. Oligonucleotide expression correlated with the regions of loss or gain of genomic material, suggesting that the changes in gene expression are related to alterations in copy number. CONCLUSION: Our study demonstrates the presence of a recurrent gain in 20q13.12 associated with overexpression of the genes located in this region, in CLL cytogenetic subgroups.

Development of wild barley (Hordeum chilense)-derived DArT markers and their use into genetic and physical mapping.

Diversity arrays technology (DArT) genomic libraries were developed from H. chilense accessions to support robust genotyping of this species and a novel crop comprising H. chilense genome (e.g., tritordeums). Over 11,000 DArT clones were obtained using two complexity reduction methods. A subset of 2,209 DArT markers was identified on the arrays containing these clones as polymorphic between parents and segregating in a population of 92 recombinant inbred lines (RIL) developed from the cross between H. chilense accessions H1 and H7. Using the segregation data a high-density map of 1,503 cM was constructed with average inter-bin density of 2.33 cM. A subset of DArT markers was also mapped physically using a set of wheat-H. chilense chromosome addition lines. It allowed the unambiguous assignment of linkage groups to chromosomes. Four segregation distortion regions (SDRs) were found on the chromosomes 2H(ch), 3H(ch) and 5H(ch) in agreement with previous findings in barley. The new map improves the genome coverage of previous H. chilense maps. H. chilense-derived DArT markers will enable further genetic studies in ongoing projects on hybrid wheat, seed carotenoid content improvement or tritordeum breeding program. Besides, the genetic map reported here will be very useful as the basis to develop comparative genomics studies with barley and model species.

Comparative genomics to bridge Vicia faba with model and closely-related legume species: stability of QTLs for flowering and yield-related traits.

This study presents the development of an enhanced map in faba bean. The map contains 258 loci, mostly gene-based markers, organized in 16 linkage groups that expand 1,875 cM, with an average inter-marker distance of 7.26 cM. The combination of EST-derived markers with a number of markers physically located or previously ascribed to chromosomes by trisomic segregation, allowed the allocation of eight linkage groups (229 markers), to specific chromosomes. Moreover, this approach provided anchor points to establish a global homology among the faba bean chromosomes and those of closely-related legumes species. The map was used to identify and validate, for the first time, QTLs controlling five flowering and reproductive traits: days to flowering, flowering length, pod length, number of seeds per pod and number of ovules per pod. Twelve QTLs stable in the 2 years of evaluation were identified in chromosomes II, V and VI. Comparative mapping suggested the conservation of one of the faba bean genomic regions controlling the character days to flowering in other five legume species (Medicago, Lotus, pea, lupine, chickpea). Additional syntenic co-localizations of QTLs controlling pod length and number of seeds per pod between faba bean and Lotus japonicus are likely. The new genetic map opens the way for further translational studies between faba bean and related legume species, and provides an efficient tool for breeding applications such as QTL analysis and marker-assisted selection.

[Bone revascularization: structural allograft intramedullary vs extramedullary. Experimental work]. / Revascularización ósea: aloinjerto estructural intramedular versus extramedular. Trabajo experimental.

INTRODUCTION: successful treatment in patients with significant bone defects secondary to infection, non-union and osteoporotic fractures resulting from previous trauma is challenging. In the current literature we did not find any reports that compare the use of intramedullary allograft boards versus the same ones placed lateral to the lesion. MATERIAL AND METHODS: we worked on a sample of 20 rabbits (2 groups of 10 rabbits each). Group 1 underwent surgery using the extramedullary allograft placement technique, while group 2 with the intramedullary technique. Four months after surgery, imaging and histology studies were performed to compare between groups. RESULTS: the analysis of the imaging studies showed a statistically significant difference between both groups with greater resorption and bone integration of the intramedullary placed allograft. Regarding histology, there were no statistically significant differences, but there was a significant prediction with a p value < 0.10 in favor of the intramedullary allograft. CONCLUSION: through our work we were able to show the great difference between the allograft placement technique with respect to imaging and histological analysis using revascularization markers. Although the intramedullary placed allograft shows us greater bone integration, the extramedullary graft will provide more support and structure in patients who require it.

INTRODUCCIÓN: el tratamiento exitoso en pacientes con importantes defectos óseos secundarios a infección, no consolidación y fracturas osteoporóticas consecuentes a traumatismos previos representa un desafío. En la literatura actual no encontramos ningún reporte que compare el uso de tablas de aloinjerto intramedular versus las mismas colocadas lateral a la lesión. MATERIAL Y MÉTODOS: se trabajó sobre una muestra de 20 conejos (dos grupos de 10 conejos cada uno). El grupo 1 fue operado mediante la técnica de colocación extramedular del aloinjerto, mientras que el grupo 2 con técnica intramedular. A los cuatro meses postquirúrgico se realizaron estudios por imágenes e histología para comparar un grupo con el otro. RESULTADOS: el análisis de los estudios por imágenes evidenció una diferencia estadísticamente significativa entre ambos grupos con mayor reabsorción e integración ósea del aloinjerto colocado intramedular. Respecto a la histología, no hubo diferencias estadísticamente significativas, pero sí una predicción significativa con p valor < 0.10 a favor del aloinjerto intramedular. CONCLUSIÓN: mediante nuestro trabajo pudimos mostrar la gran diferencia que hay entre la técnica de colocación del aloinjerto respecto al análisis imagenológico e histológico utilizando marcadores de revascularización. Si bien el aloinjerto colocado de manera intramedular nos muestra mayor integración ósea, el injerto extramedular brindará más soporte y estructura en pacientes que así lo requieran.

High success and low recurrence with shorter treatment regimen for multidrug-resistant TB in Nepal.

SETTING: Nine drug-resistant TB centres, some of them supported by Damien Foundation in Nepal where >80% of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) patients are treated. OBJECTIVE: To assess the uptake, effectiveness and safety of the 9-12-month shorter treatment regimen (STR) in MDR/RR-TB patients registered from January 2018 to December 2019. DESIGN: This was a cohort study involving secondary programme data. RESULTS: Of 631 patients, 301 (48.0%) started and continued STR. Key reasons for ineligibility to start/continue STR were baseline resistance or exposure to second-line drugs (62.0%), contact with extensively drug-resistant TB (XDR-TB) or pre-XDR-TB (7.0%) patients and unavailability of STR drugs (6.0%). Treatment success was 79.6%; unsuccessful outcomes were death (12.0%), lost to follow-up (5.3%), failure (2.7%) and not evaluated (0.7%). Unsuccessful outcomes were significantly associated with HIV positivity and patient age ⩾55 years, with adjusted relative risk of respectively 2.39 (95% CI 1.52-3.77) and 3.86 (95% CI 2.30-6.46). Post-treatment recurrence at 6 and 12 months was respectively 0.5% and 2.4%. Serious adverse events (SAEs) were seen in 15.3% patients - hepatotoxicity and ototoxicity were most common. CONCLUSION: STR had a modest uptake, high treatment success and low post-treatment recurrence. For proper detection and management of SAEs, improving pharmacovigilance might be considered. Availability of rapid diagnostic test for second-line drugs is crucial for correct patient management.

CADRE: Neuf centres de traitement de la TB pharmacorésistante, dont certains sont financés par Action Damien au Népal où >80% des patients atteints de TB multirésistante/résistante à la rifampicine (MDR/RR-TB) sont traités. OBJECTIF: Évaluer l'utilisation, l'efficacité et l'innocuité d'un schéma thérapeutique plus court (STR) de 9-12 mois chez les patients atteints de MDR/RR-TB enregistrés de janvier 2018 à décembre 2019. MÉTHODE: Étude de cohorte comprenant des données programmatiques secondaires. RÉSULTATS: Sur 631 patients, 301 (48,0%) ont démarré et poursuivi un STR. Les raisons principales d'inéligibilité à l'instauration/la poursuite d'un STR étaient une résistance initiale ou une exposition aux médicaments de deuxième intention (62,0%), un contact avec des patients atteints de TB ultrarésistante (XDR-TB) ou de pré-XDR-TB (7,0%) et la non-disponibilité des médicaments pour le STR (6,0%). Le taux de réussite thérapeutique était de 79,6%. Les résultats liés à la non-réussite thérapeutique étaient décès (12,0%), perte de vue (5,3%), échec thérapeutique (2,7%) et absence d'évaluation (0,7%). Les résultats liés à la non-réussite thérapeutique étaient significativement associés à l'infection par le VIH et aux patients âgés ⩾55 ans avec un risque relatif ajusté de 2,39 (IC 95% 1,52­3,77) et de 3,86 (IC 95% 2,30­6,46), respectivement. Le taux de récidive post-traitement à 6 et 12 mois était de 0,5% et 2,4%, respectivement. Des évènements indésirables graves (SAE) ont été observés chez 15,3% des patients, le plus souvent hépatotoxicité et ototoxicité. CONCLUSION: Le STR a été associé à une utilisation modérée, à une réussite thérapeutique élevée et à un faible taux de récidive post-traitement. Pour une détection et une prise en charge adéquates des SAE, l'amélioration de la pharmacovigilance peut être envisagée. La disponibilité de tests diagnostiques rapides pour les médicaments de deuxième intention est essentielle à une prise en charge adéquate des patients.

Low yield but high levels of multidrug resistance in urinary tract infections in a tertiary hospital, Nepal.

SETTING: There are concerns about the occurrence of multidrug resistance (MDR) in patients with urine tract infections (UTI) in Nepal. OBJECTIVE: To determine culture positivity, trends in MDR among Escherichia coli and Klebsiella pneumoniae infections and seasonal changes in culture-positive UTI specimens isolated from 2014 to 2018 at the B P Koirala Institute of Health Sciences, Dharan, Eastern Nepal. DESIGN: This was a cross-sectional study using secondary laboratory data. RESULTS: Among 116,417 urine samples tested, 19,671 (16.9%) were culture-positive, with an increasing trend in the number of samples tested and culture positivity. E. coli was the most common bacteria (54.3%), followed by K. pneumoniae (8.8%). Among E. coli and K. pneumoniae isolates, MDR was found in respectively 42.5% and 36.0%. MDR was higher in males and people aged >55 years, but showed a decreasing trend over the years. The numbers of isolates increased over the years, with a peak always observed from July to August. CONCLUSION: Low culture positivity is worrying and requires further work into improving diagnostic protocols. Decreasing trends in MDR are a welcome sign. Information on seasonal changes that peak in July-August can help laboratories better prepare for this time with adequate buffer stocks to ensure culture and antibiotic susceptibility testing.

CONTEXTE: La résistance à plusieurs médicaments (MDR) chez les patients atteints d'infections urinaires (UTI) au Népal est un sujet de préoccupations. OBJECTIF: Déterminer le taux de positivité des cultures, les tendances de MDR parmi les infections à Escherichia coli et Klebsiella pneumoniae et les variations saisonnières dans les échantillons d'UTI positifs par culture de 2014 à 2018 au BP Koirala Institute of Health Sciences, Dharan, Népal oriental. MÉTHODE: Il s'agissait d'une étude transversale réalisée en utilisant des données de laboratoire secondaires. RÉSULTATS: Parmi les 116 417 échantillons urinaires testés, 19 671 (16,9%) étaient positifs par culture, avec une tendance à la hausse du nombre d'échantillons testés et du taux de positivité par culture. E. coli était la bactérie la plus fréquente (54,3%), suivie de K. pneumoniae (8,8%). Une MDR a été observée chez respectivement 42,5% et 36,0% des isolats de E. coli et de K. pneumoniae. La MDR était plus élevée chez les hommes et les personnes âgées >55 ans, mais une tendance à la baisse a été observée au fil des ans. Le nombre d'isolats a augmenté au fil des ans, avec un pic toujours observé de juillet à août. CONCLUSION: Le faible taux de positivité par culture est préoccupant et d'autres études sont nécessaires pour améliorer les protocoles diagnostiques. Les tendances à la baisse en matière de MDR sont un signe encourageant. Les informations relatives aux variations saisonnières avec un pic en juillet-août peuvent aider les laboratoires à mieux se préparer en prévision de cette période, en renouvelant les stocks de solutions tampons afin de pouvoir réaliser les cultures et les tests de sensibilité aux médicaments.

[Model of care for the treatment of patients with osteoarthritis from the first to the third level]. / Modelo de atención para el tratamiento de pacientes con osteoartritis del primer al tercer nivel.

INTRODUCTION: Osteoarthritis in Mexico is one of the ten most frequent causes of disability. Early diagnosis and detection of risk factors are determinant for treatment. The institutional organization establishes therapeutic guidelines according to each level of care, but effective management is not achieved. MATERIAL AND METHODS: A prospective, pilot, interventional, clinical study was conducted, which included patients diagnosed with different degrees of knee osteoarthritis in the first, second and third level of care, with an integrative model that includes a group of professionals for the intervention of nutritional, physiotherapeutic, social and psychological evaluation from the first level. RESULTS: The intervention of a multidisciplinary care group allows a correct evaluation and assignment of the level of care, optimizing human and material resources. The participation of different disciplines in nutrition, psychology, social work, physiotherapy and rehabilitation modifies the global lifestyle by involving the patients themselves in their treatment. The intervention group had improvements in the visual analog pain scale, mobility arcs, low body mass index and improvement in the psychological aspect. CONCLUSIONS: The proposed model of care demonstrates that implementation in the institution and in each clinical care unit should be considered to improve outcomes.

INTRODUCCIÓN: La osteoartritis en México es una de las 10 causas más frecuentes de discapacidad. El diagnóstico temprano y la detección de factores de riesgo son determinantes para el tratamiento. La organización institucional establece las pautas terapéuticas de acuerdo con cada nivel de atención, pero no se logra un manejo efectivo. MATERIAL Y MÉTODOS: Se realizó un estudio prospectivo, piloto, de intervención, clínico conformado por pacientes diagnosticados con diferentes grados de osteoartritis de rodilla en el primer, segundo y tercer nivel de atención, con un modelo integrador que incluyó un grupo de profesionales para la intervención de la evaluación nutricional, fisioterapéutica, social y sicológica desde el primer nivel. RESULTADOS: La intervención de un grupo de atención multidisciplinaria permite una correcta evaluación y asignación del nivel de atención optimizando los recursos humanos y materiales. La participación de diferentes disciplinas en nutrición, sicología, trabajo social, fisioterapia y rehabilitación modifica el estilo de vida global al involucrar a los propios pacientes en su tratamiento. El grupo de intervención tuvo mejoras en la escala de dolor análogo visual, arcos de movilidad, bajo índice de masa corporal y mejoría en el aspecto sicológico. CONCLUSIONES: El modelo de atención propuesto demuestra que la implementación en la institución y en cada unidad clínica de atención debe considerarse para mejorar los resultados.

[Application of vancomycin powder on graft. Does the fusion of the rabbits spine is affected?] / Aplicación de vancomicina en polvo sobre el injerto. ¿Afecta la fusión de columna en conejos?

INTRODUCTION: In vitro studies suggest that vancomycin is highly cytotoxic for osteoblasts. However, several clinical studies in vivo have not provided evidence or determined that effect on osteogenesis. The aim of this work was to investigate the effect of topical vancomycin on a lumbar arthrodesis model on New Zealand white rabbits. MATERIAL AND METHODS: Double-blind randomized experimental study. Posterolateral spinal fusion was performed on 30 rabbits, divided into two groups, A: graft/placebo, B: graft/vancomycin. After sacrificing them, the bone callus was evaluated with axial tomography and classified into three groups: no fusion (0), partial/incomplete fusion (1) and fusion (2). The samples were also histologically analyzed. The associations between the presence of fusion (complete/incomplete) and the group tested were estimated using Poisson log-linear models with two covariates. Adherences to histologically obtained responses were studied using contingency tables and 2 tests. The significance level was set equal to 0.05. RESULTS: Treatment with vancomycin has 30% (0.30. CI 95%: 0.12-0.94) less chance compared to the placebo group, of presenting complete fusion. In other words, the vancomycin group has 2.3 times (CI 95%: 1.02-4.91) more likelyhood, compared to placebo, to have incomplete fusion. CONCLUSION: The application of vancomycin powder mixed with graft reduces fusion rates by 30%, but at doses 5 times higher than those routinely used in arthrodesis by the authors medical team.

INTRODUCCIÓN: Estudios in vitro sugieren que la vancomicina es altamente citotóxica para los osteoblastos. No obstante, diversos estudios clínicos in vivo no han aportado evidencias o determinado ese efecto en la osteogénesis. El objetivo del presente trabajo fue investigar el efecto de la vancomicina tópica, en un modelo de artrodesis lumbar sobre conejos blancos neozelandeses. MATERIAL Y MÉTODOS: Estudio experimental randomizado doble ciego. Se realizó fusión espinal posterolateral a 30 conejos, divididos en dos grupos, A: injerto/placebo, B: injerto/vancomicina. Luego de sacrificarlos, se evaluó el callo óseo con tomografía axial, clasificándolos en tres grupos: sin fusión (0), fusión parcial/incompleta (1) y fusión (2). Las muestras también fueron analizadas histológicamente. Las asociaciones entre presencia de fusión (completa/incompleta) y el grupo ensayado fueron estimadas con modelos log-lineales de Poisson con dos covariables. Las adherencias con las respuestas obtenidas histológicamente fueron estudiadas usando tablas de contingencia y test 2. El nivel de significación se fijó igual a 0.05. RESULTADOS: El tratamiento con vancomicina tiene 30% (0.30. IC 95%: 0.12-0.94) menos probabilidad respecto al grupo placebo de presentar fusión completa. En otros términos, el grupo vancomicina tiene 2.3 veces (IC 95%: 1.02-4.91) más probabilidad, respecto del placebo, de tener fusión incompleta. CONCLUSIÓN: La aplicación de vancomicina en polvo mezclada con injerto reduce 30% las tasas de fusión, pero a dosis cinco veces más alta que las usadas rutinariamente en artrodesis por el equipo médico de los autores.

Renoportal anastomosis as a rescue technique in postoperative portal thrombosis in liver transplantation.

Renoportal anastomosis has been used as the primary portal revascularization technique in grade 4 portal thrombosis, but never after posttransplant portal thrombosis. A cirrhotic patient with hepatocellular carcinoma and partial portal thrombosis of two-thirds of the lumen was transplanted. The thrombus was removed and good portal flow obtained upon reperfusion (2.8 L/min). On the ninth postoperative day Doppler ultrasound revealed complete portal thrombosis extending from the splenomesenteric confluence. At emergency reoperation, we removed the newly formed thrombus. Portal vein branches were flushed with heparin and urokinase. After reconstruction of the anastomosis, we achieved a flow of 1.1 L/min. Rethrombosis occurred again on day 13. At reoperation, thrombus was removed again. However, this time portal flow was not recovered, due to hepatofugal flow associated with both the presence of collaterals and pancreatic edema. A left renoportal anastomosis was performed using an interposed iliac vein graft. A catheter was placed into the portal vein through a recanalization of the umbilical vein of the graft. After urokinase perfusion, portal inflow was 1.7 L/min. The postoperative course was satisfactory, with progressive normalization of liver tests and no further thrombosis. Persistent ascites improved with treatment. Angiography on day 41 showed good portal flow from the renal vein, with uniform distribution within the liver. A renoportal anastomosis can be useful for recovery of liver failure after posttransplant portal thrombosis, in the absence of portal flow.

Multi-antigenic recombinant subunit vaccine against Lawsonia intracellularis: The etiological agent of porcine proliferative enteropathy.

Proliferative enteropathy, caused by Lawsonia intracellularis, represents a threat for swine industry. Current vaccines are effective but difficult to obtain and scaled up, because of demanding bacterial culture conditions. In this work, a subunit vaccine candidate against L. intracellularis was developed and its efficacy was evaluated in vivo, alone or co-formulated with pig recombinant IFN-α. The vaccine formulation contains three chimeric antigens: two outer membrane proteins and a secreted one, which were engineered by adding T epitopes using bioinformatics tools. After simultaneously expressing the three antigens in E. coli, its immunogenicity was tested in mice and pigs. Antigens co-formulated with porcine IFN-α were also assayed in the last species. Immune response was assessed by ELISA and qPCR, and histopathological studies of intestinal epithelial tissue were performed after challenge. Mice and pigs showed an increased IgG response against chimeric antigens. Particularly, there were significant differences in the antibody response when porcine IFN-α was co-administrated with L. intracellularis antigens. Besides, mRNAs from il12 and cd4 marker were detected during the first week after immunization of pigs, suggesting a Th1-type cellular immune response. The significant enhancement of oas2 gene expression indicates the effect exerted by porcine IFN-α. Post-mortem histopathological analysis post-challenge revealed damage only into epithelial cells of the gastrointestinal tract from animals of the negative control group. Injuries were related to atrophy of the intestinal villi, where a decrease of globet cells and a greater migration of lymphocytes were observed. Overall, our results demonstrated that the vaccine candidate elicited significant humoral and cellular immune responses. Besides, histopathological analysis suggested that vaccinated animals were protected against experimental L. intracellularis infection. This research constitutes a step forward to the generation of the first recombinant chimeric vaccine against L. intracellularis, representing a faster, easier and cost effective approach to counteract the porcine proliferative enteropathy.