Clinical and Genetic Analysis of Patients With TK2 Deficiency.

Objectives: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive disorder that stems from a perturbation of the mitochondrial DNA maintenance. Nucleoside treatment has recently shown promise as a disease-modifying therapy. TK2d was initially associated with rapidly progressive fatal myopathy in children featuring mitochondrial DNA depletion. Subsequently, less severe variants of the disease were described, with onset of symptoms during adolescence or adulthood and associated with the presence of multiple mtDNA deletions. These less severe phenotypes have been reported in only 15% of the approximately 120 patients described worldwide. However, some reports suggest that these juvenile and adult-onset presentations may be more common. The objective of this study was to describe the clinical phenotype in a sample of patients from Spain. Methods: This study includes 53 patients harboring biallelic TK2 pathogenic variants, compiling data retrospectively from 7 Spanish centers. We analyzed allele frequency, investigated the most recent common ancestor of core haplotypes, and used the Runs of Homozygosity approach to investigate variant coalescence. Results: Symptom onset distribution revealed that 32 patients (60%) experienced symptoms beyond 12 years of age. Approximately 30% of patients died of respiratory insufficiency, while 56% of surviving patients needed mechanical ventilation. Genetic analysis identified 16 distinct variants in TK2. Two variants, p.Lys202del and p.Thr108Met, exhibited significantly higher prevalence in the Spanish population than that reported in gnomAD database (86-fold and 13-fold, respectively). These variants are estimated to have originated approximately 16.8 generations ago for p.Thr108Met and 95.2 generations ago for p.Lys202del within the Spanish population, with the increase in frequency attributed to various forms of inbreeding. In late-onset cases, 46.9% carried the p.Lys202del variant. Discussion: The higher frequency of TK2d in Spain can be partially attributed to the increased prevalence of 2 variants and consanguinity. Notably, in 60% of the cohort, the disease was late-onset, emphasizing the potential underdiagnosis of this subgroup of patients in other regions. Raising awareness of this potentially treatable disorder is of utmost importance because early interventions can significantly affect the quality of life and survival of affected individuals.

A comprehensive examination of small-bowel capsule endoscopy in Spanish centers to meet European Society of Gastrointestinal Endoscopy standards.

Background and study aims In 2019, the European Society of Gastrointestinal Endoscopy (ESGE) created a working group to develop technical and quality standards for small-bowel capsule endoscopy (SBCE) to improve the daily practice of endoscopy services. They developed 10 quality parameters, which have yet to be tested in a real-life setting. Our study aimed to evaluate the accomplishment of the quality standards in SBCE established by the ESGE in several Spanish centers. Materials and methods An online survey of 11 multiple-choice questions related to the ESGE performance measures was sent to Spanish centers with experience in SBCE. In order to participate and obtain reliable data, at least 100 questionnaires had to be answered per center because that is the minimum number established by ESGE. Results 20 centers participated in the study, compiling 2049 SBCEs for the analysis. Only one of 10 performance measures (cecal visualization) reached the minimum standard established by the ESGE. In five of 10 performance measures (Indication, lesion detection rate, terminology, and retention rate) the minimum standard was nearly achieved. Conclusions Our study is the first multicenter study regarding SBCE quality performance measures in a real setting. Our results show that the minimum standard is hardly reached in most procedures, which calls into question their clinical applicability in real life. We suggest performing similar studies in other countries to evaluate whether there is a need for quality improvement programs or a need to reevaluate the minimum and target values published so far.

Gene Co-Expression Networks Offer New Perspectives on Sepsis Pathophysiology.

Sepsis is among the most common causes of death in intensive care units. Septic shock is a type of circulatory shock that shows signs and symptoms that are similar to non-septic shock. Despite the impact of shock on patients and the economic burden, knowledge of the pathophysiology of septic shock is scarce. In this context, weighted gene co-expression network analysis can help to elucidate the molecular mechanisms of this condition. The gene expression dataset used in this study was downloaded from the Gene Expression Omnibus, which contains 80 patients with septic shock, 33 patients with non-septic shock, and 15 healthy controls. Our novel analysis revealed five gene modules specific for patients with septic shock and three specific gene modules for patients with non-septic shock. Interestingly, genes related to septic shock were mainly involved in the immune system and endothelial cells, while genes related to non-septic shock were primarily associated with endothelial cells. Together, the results revealed the specificity of the genes related to the immune system in septic shock. The novel approach developed here showed its potential to identify critical pathways for the occurrence and progression of these conditions while offering new treatment strategies and effective therapies.

Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis.

Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifying genetic markers that can predict a patient's response to MTX. However, the field of MTX pharmacogenetics is still in its early stages and there is a lack of consistency among studies. This study aimed to identify genetic markers associated with MTX efficacy and toxicity in a large sample of RA patients, and to investigate the role of clinical covariates and sex-specific effects. Our results have identified an association of ITPA rs1127354 and ABCB1 rs1045642 with response to MTX, polymorphisms of FPGS rs1544105, GGH rs1800909, and MTHFR genes with disease remission, GGH rs1800909 and MTHFR rs1801131 polymorphisms with all adverse events, and ADA rs244076 and MTHFR rs1801131 and rs1801133, However, clinical covariates were more important factors to consider when building predictive models. These findings highlight the potential of pharmacogenetics to improve personalized treatment of RA, but also emphasize the need for further research to fully understand the complex mechanisms involved.

Frequency, location, and diameter of the anastomosis between the posterior superior alveolar artery and the infraorbital artery in imaging studies: systematic review and meta-analysis.

The anastomosis between the posterior superior alveolar artery (PSAA) and the infraorbital artery (IOA) courses along half of the lateral wall of the maxillary sinus. Risk of injury to the anastomosis between PSAA and IOA during surgical procedures has been reported. The aim of the present study was to carry out a systematic review and meta-analysis to determine the frequency, location, and diameter of the anastomosis between PSAA and IOA in imaging studies (cone-beam computed tomography, spiral cone-beam computed tomography, and computed tomography). A search was carried out in the PubMed, EMBASE, and LILACS. Original works were included reporting imaging studies to analyze the frequency, location, and diameter of the anastomosis in humans. The risks of bias were analyzed using the AQUA tool. Generalized linear mixed models were used to estimate the frequency and the 95% CI in the meta-analysis. The variance in prevalence estimates was stabilized by logit transformation. The qualitative analysis included 49 studies with 10,837 patients. The frequency of the anastomosis between PSAA and IOA was 74% (prediction interval 0.20-0.97%). The anastomosis was most frequently located in the intraosseous region (60.0%), followed by the submembranous region (33.0%), and least frequently in an extraosseous location (5.0%). Arteries with diameter of 1.0-1.9 mm were most frequent (32.0%), followed by arteries with diameter less than 1 mm (23.0%); a small number with diameter greater than 2 mm was recorded (4.0%). These data can be used as a reference to help surgeons when planning interventions in the lateral wall of the maxillary sinus. Registration number: INPLASY, number 202120071.

Influence of Renal Dysfunction on the Differential Behaviour of Procalcitonin for the Diagnosis of Postoperative Infection in Cardiac Surgery.

Background: procalcitonin is a valuable marker in the diagnosis of bacterial infections; however, the impairment of renal function can influence its diagnostic precision. The objective of this study is to evaluate the differential behaviour of procalcitonin, as well as its usefulness in the diagnosis of postoperative pulmonary infection after cardiac surgery, depending on the presence or absence of impaired renal function. Materials and methods: A total of 805 adult patients undergoing cardiac surgery with extracorporeal circulation (CBP) were prospectively recruited, comparing the behaviour of biomarkers between the groups with and without postoperative pneumonia and according to the presence or absence of renal dysfunction. Results: Pulmonary infection was diagnosed in 42 patients (5.21%). In total, 228 patients (28.32%) presented postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, even in the presence of renal dysfunction. The optimal procalcitonin threshold differed markedly in patients with renal dysfunction compared to patients without renal dysfunction (1 vs. 0.78 ng/mL p < 0.05). The diagnostic accuracy of procalcitonin increased significantly when the procalcitonin threshold was adapted to renal function. Conclusions: Procalcitonin is an accurate marker of postoperative infection in cardiac surgery, even in the presence of renal dysfunction. Renal function is an important determinant of procalcitonin levels and, therefore, its diagnostic thresholds must be adapted in the presence of renal dysfunction.

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation.

Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and Methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.

Novel genes and sex differences in COVID-19 severity.

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Dolutegravir plus rilpivirine: benefits beyond viral suppression: DORIPEX retrospective study.

ABSTRACT: Switching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.A multicentric retrospective cohort study.Treatment-experienced virologically suppressed HIV-1-infected patients who were switched to DTG plus RPV were included. Using different models for paired data, we evaluated the efficacy and immune status in terms of CD4+ and CD8+ T-cell counts and CD4/CD8 ratio at 24 and 48 weeks of treatment.The study population comprised of 524 patients from 34 centers in Spain. Men accounted for 76.9% of patients, with a median age of 53 years. Patients receiving DTG plus RPV reached weeks 24 and 48 in 99.4% and 83.8% of cases, respectively, with only three (0.57%) virological failures. We found a significant decrease in CD8+ T-cell count (log OR -40) at week 24 and an increase in CD4+ T-cell count at week 48 (log OR +22.8). In acquired immunodeficiency syndrome-diagnosed patients, we found a significant increase in the CD4+ T-cell count at week 48 (log OR = 41.7, P = .0038), but no significant changes in the CD8+ T-cell count (log OR = -23.4, P = .54). No differences were found in the CD4/CD8 ratio between the acquired immunodeficiency syndrome subgroup and sex or age.In patients with controlled treatment, dual therapy with DTG plus RPV slightly improved the immune status during the first 48 weeks after switching, not only in terms of CD4+ T-cell count but also in terms of CD8+ T-cell count, with persistently high rates of viral control.

Plasma miRNA profile at COVID-19 onset predicts severity status and mortality.

BACKGROUND: MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to analyze the plasma miRNA profile at COVID-19 onset to identify miRNAs as early prognostic biomarkers of severity and survival. METHODS AND RESULTS: Plasma miRNome of 96 COVID-19 patients that developed asymptomatic/mild, moderate and severe disease was sequenced together with a group of healthy controls. Plasma immune-related biomarkers were also assessed. COVID-19 patients showed 200 significant differentially expressed (SDE) miRNAs concerning healthy controls, with upregulated putative targets of SARS-CoV-2, and inflammatory miRNAs. Among COVID-19 patients, 75 SDE miRNAs were observed in asymptomatic/mild compared to symptomatic patients, which were involved in platelet aggregation and cytokine pathways, among others. Moreover, 137 SDE miRNAs were identified between severe and moderate patients, where miRNAs targeting the SARS CoV-2 genome were the most strongly disrupted. Finally, we constructed a mortality predictive risk score (miRNA-MRS) with ten miRNAs. Patients with higher values had a higher risk of 90-days mortality (hazard ratio = 4.60; p-value < 0.001). Besides, the discriminant power of miRNA-MRS was significantly higher than the observed for age and gender (AUROC = 0.970 vs. 0.881; p = 0.042). CONCLUSIONS: SARS-CoV-2 infection deeply disturbs the plasma miRNome from an early stage of COVID-19, making miRNAs highly valuable as early predictors of severity and mortality.

Anastomosis between the posterior superior alveolar artery and the infra-orbital artery: a review of current terminology / Anastomosis entre la arteria alveolar superior posterior y la arteria infra-orbital: una revisión de la terminología actual

SUMMARY: The posterior superior alveolar artery (PSAA) and the infra-orbital artery (IOA) present intraosseous and extraosseous rami which form an anastomosis in the lateral wall of the maxillary sinus. This anastomosis is always present, however it has not yet been included in anatomical terminology (AT), and different terms are used in scientific communication to refer to it. The aim of this study was to carry out a review of the different terms used to name this vascular structure. A literature review was carried out on the terms used to name the anastomosis between the PSAA and IOA in imaging studies and human cadavers that assessed the presence/frequency of this anatomical structure. The search was carried out in the Medline, EMBASE and LILACS databases, in Portuguese, Spanish and English, with no date restrictions. Qualitative analysis was applied to the studies selected, analysing the terminology used to refer to the anastomosis between the PSAA and IOA. Of the 2108 original articles found, 60 were selected as potentially relevant and 54 studies were finally included for qualitative analysis. Sixteen terms were found to refer to the anastomosis between the PSAA and IOA, the most frequent being Posterior Superior Alveolar Artery (PSAA), followed by Alveolar Antral Artery (AAA). Many terms are used in the medical literature to designate the anastomosis between the PSAA and IOA, the most frequent being PSAA and AAA. There is a need to unify the terms used to designate this vascular structure, and to incorporate the selected term into anatomical terminology, in order to avoid confusion in scientific communication.

RESUMEN: La arteria alveolar superior posterior (AASP) y la arteria infra-orbital (AIO) tienen ramas intra y extra óseas que forman una anastomosis en la pared lateral del seno maxilar. Esta anastomosis está siempre presente, sin embargo, aún no ha sido incluida en la terminología anatómica (TA), por lo que en la comunicación científica se utilizan diferentes términos para referirse a ella. El objetivo de este estudio fue realizar una revisión sobre los diferentes términos utilizados para nombrar esta estructura vascular. Se realizó una revisión de la literatura sobre los términos utilizados para nombrar la anastomosis entre AASP y AIO en estudios imagenológicos y en cadáveres humanos que evaluaron la presencia/frecuencia de esta estructura anatómica. La búsqueda fue realizada en las bases de datosMedline, EMBASE y LILACS, en los idiomas portugués, español e inglés, sin restricción de fecha. Los estudios seleccionados fueron evaluados de forma cualitativa, analizando la terminología empleada para referirse a la anastomosis entre AASP y AIO. Fueron encontrados 2108 artículos originales, siendo seleccionados 60 artículos potencialmente relevantes y finalmente fueron incluidos 54 estudios para análisis cualitativo. Fueron encontrados 16 términos para referirse a la anastomosis entre AASP y AIO, siendo AASP el más frecuente seguido de arteria alveolo-antral (AAA). Son muchos los términos utilizados en la literatura médica para designar la anastomosis entre AASP y AIO, siendo AASP y AAA los más usados. La unificación de los términos utilizados para designar esta estructura vascular y su incorporación en la Terminología Anatómica contribuiría a evitar equívocos en la comunicación científica.

Implication of mucus-secreting cells, acidophilic granulocytes and monocytes/macrophages in the resolution of skin inflammation caused by subcutaneous injection of λ/κ-carrageenin to gilthead seabream (Sparus aurata) specimens.

To date, the mechanisms of inflammation have been poorly studied in fish of commercial interest, due to the lack of development of appropriate experimental models. The current study evaluated a local inflammation triggered by a polymeric carrageenin mixture (a mucopolysaccharide derived from the red seaweed Chondrus crispus) in the skin of gilthead seabream (Sparus aurata). Fish were injected subcutaneously with phosphate-buffered saline (as control) or λ/κ-carrageenin (1%), and skin samples from the injection sites were collected 1.5, 3 and 6 hr post-injection, processed for inclusion in paraplast and stained with haematoxylin-eosin, Alcian blue or periodic acid-Schiff. Furthermore, immunohistochemistry and expression analyses of several cells' markers and proinflammatory genes were also analysed in samples of the injected sites. Microscopic results indicated an increased number of skin mucus-secreting cells and acidophilic granulocytes in the skin of fish studied at 1.5 hr and 3 hr post-injection with carrageenin, respectively, with respect to the data obtained in control fish. Otherwise, both the gene expression of the non-specific cytotoxic cell marker (granzyme B, grb) and the proinflammatory cytokine (interleukin-1ß, il-1ß) were up-regulated at 1.5 hr in the skin of fish injected with carrageenin compared with the control fish, whilst the gene expression of acidophilic granulocyte markers (NADPH oxidase subunit Phox22 and Phox40, phox22 and phox40) was up-regulated at 3 and 6 hr in the carrageenin group, compared with the control group. In addition, the gene expression of myeloperoxidase (mpo) was also up-regulated at 6 hr in the skin of fish injected with carrageenin in comparison with control samples. The present results indicate the chronological participation of two important immune cells involved in the resolution of the inflammation in the skin of gilthead seabream.

Differences in the hepatitis C virus cascade of care and time to initiation of therapy among vulnerable subpopulations using a mobile unit as point-of-care.

BACKGROUND AND AIMS: People who inject drugs (PWID) and other marginalized populations with high hepatitis C virus (HCV) infection rates represent a unique challenge for treatment initiation due to health, administrative and social barriers. We analysed the HCV cascade of care (CoC) in some vulnerable subpopulations in Madrid, Spain, when using a mobile point-of-care (PoC). METHODS: From 2019 to 2021, a mobile unit was used to screen active HCV using a linkage-to-care and two-step PoC-based strategy. Viremic participants were grouped into four subgroups: PWID, homeless individuals and people with a mental health disorder (MHD) and alcohol use disorder (AUD). Logistic regression, and Cox and Aalen's additive models were used to analyse associated factors and differences between groups. RESULTS: A prospectively recruited cohort of 214 HCV-infected individuals (73 PWID, 141 homeless, 57 with a MHD and 91 with AUD) participated in the study. The overall HCV CoC analysis found that 178 (83.1%) attended a hospital, 164 (76.6%) initiated direct-acting antiviral therapy and 141 (65.8%) completed therapy, of which 99 (95.2%) achieved sustained virological response (SVR). PWID were significantly less likely to initiate treatment, whereas individuals with AUD waited longer before starting the treatment. Both people with AUD and PWID were significantly less likely to complete HCV treatment. CONCLUSIONS: Overall, SVR was achieved in the majority of the participants treated. However, PWID need better linkage to care and treatment, whereas PWID and AUD need more support for treatment completion.

Sex estimation by metric analysis of the angle of mandible and the mandibular ramus: a systematic review / Estimación sexual mediante análisis métrico del ángulo de la mandíbula y de la rama mandibular: revisión sistemática

SUMMARY: Sex estimation is the first step in human identification. The mandibular ramus and the condyle have been widely used as indicators for sexual diagnosis because they are regions that undergo important morphological changes which increase sexual dimorphism. The object of the present study was to carry out a systematic review to determine the metric parameters of the mandibular ramus that present the greatest sexual dimorphism, and to sex estimation from the angle of mandible (MA). We included documents in English, Spanish and Portuguese which analysed sex estimation or sex diagnosis by metric analysis of the mandibular ramus in humans. The search was conducted in PubMed/MEDLINE, EMBASE, LILACS, up to December 2020. The risks of bias were analysed using the AQUA tool. The search identified 538 studies. After exclusion of duplicates and irrelevant articles, 39 studies were included for qualitative analysis. Of these, 18 studies were carried out on dry mandibles and 21 by imaging techniques, totalling 7270 participants of 14 different nationalities. We found 14 sex-estimation parameters in the mandibular ramus, plus the MA. Sex estimation by the MA is variable; it is a good predictor only for some populations. The height of the mandibular ramus, the angle of mandible, the bicondylar angle and the height of the coronoid process were the estimation parameters cited in the greatest number of studies. The mandibular ramus presents great sexual dimorphism and can be used as a sex predictor in different populations. Although some parameters of the mandibular ramus can present accuracy of almost 80 % when analysed in isolation, more accurate sex estimation is achieved when the parameters are analysed in conjunction.

RESUMEN: La estimación sexual es el primer paso en la identificación humana. La rama mandibular y el cóndilo se han utilizado ampliamente como indicadores para el diagnóstico sexual debido a que son regiones que sufren cambios morfológicos importantes, aumentando el dimorfismo sexual. El objetivo del presente estudio fue realizar una revisión sistemática a fin de determinar los parámetros métricos de la rama mandibular que presentan mayor dimorfismo sexual, bien estimar el sexo a través del ángulo de la mandíbula (AM). Se incluyeron artículos en Inglés, Español y Portugués que analizaron la predicción sexual o el diagnóstico sexual mediante análisis métrico de la rama mandibular en humanos. La búsqueda fue realizada a través de PubMed/MEDLINE, EMBASE, LILACS, con límite hasta Diciembre 2020. El análisis de los riesgos de sesgos se realizó con la herramienta AQUA. Fueron identificados 538 estudios. Tras la exclusión de duplicados y estudios fuera del tema fueron incluidos 39 estudios para análisis cualitativa. De estos, 18 estudios fueron realizados en mandíbulas secas y 21 en exámenes de imagen, totalizando 7270 participantes de 14 nacionalidades distintas. Fueron encontrados 14 parámetros predictores del sexo en la rama mandibular más el AM. La predicción sexual a través del AM es variable, siendo un buen predictor solamente para algunas poblaciones. La altura de la rama mandibular, ángulo bigoníaco, ángulo bicondilar y la altura del proceso coronoides fueron los parámetros predictivos citados en mayor número de estudios. La rama mandibular presenta gran dimorfismo sexual y puede ser utilizada como predictor del sexo en diferentes poblaciones. A pesar que algunos parámetros de la rama mandibular pueden presentar una precisión de casi 80 % cuando analizadas de forma aislada, una mayor predicción sexual es alcanzada cuando los parámetros son analizados en conjunto.

Oral ingestion versus endoscopic delivery of endoscopic capsule in patients with previous gastrointestinal surgery (ORENCES study): A Spanish multicentre observational study / Ingesta oral versus colocación endoscópica de la cápsula endoscópica en pacientes con cirugía gastrointestinal previa (estudio ORENCES): un estudio observacional multicéntrico español

Background: Small Bowel Capsule Endoscopy is the first-choice technique for investigating the majority of small bowel diseases. Its most common complications are related to incomplete examinations and capsule retention. There is no consensus on how patients with previous gastrointestinal surgery should receive the capsule. Objective: The primary endpoint was to compare the rate of complete small-bowel examinations (completion rate) between oral ingestion and endoscopic delivery of the capsule. The secondary endpoint was to compare diagnostic yield and adverse events in the two groups. Methods: A retrospective observational study was conducted in nine hospitals in Spain. Demographic data, previous surgery, indication for capsule endoscopy, intestinal transit time, diagnosis, completion rate (percentage of capsules reaching the caecum), diagnostic yield (percentage of results compatible with indication for the exam) and adverse events were collected. Results: From January 2009 to May 2019 fifty-seven patients were included (39 male, mean age 66±15 years). The most common indications for the exam were “overt” (50.9%) and “occult” (35.1%) small bowel bleeding. Previous Billroth II gastrectomy and Roux-en-Y gastric bypass were present in 52.6% and 17.5% of patients respectively. The capsule was swallowed in 34 patients and placed endoscopically in 23 patients. No significant differences were observed between the oral ingestion and endoscopic delivery groups in terms of completion rate (82.4% vs. 78.3%; p=0.742), diagnostic yield (41.2% vs. 52.2%; p=0.432) or small bowel transit time (301 vs. 377min, p=0.118). No capsule retention occurred. Only one severe adverse event (anastomotic perforation) was observed in the endoscopic delivery group. Conclusions: In our case series, there were no significant differences between oral ingestion and endoscopic delivery in terms of completion rate, diagnostic yield or safety.(AU)

Antecedentes: La cápsula endoscópica representa la técnica de primera elección para investigar la mayoría de las enfermedades del intestino delgado. Sus complicaciones más comunes frecuentes son las exploraciones incompletas y la retención a nivel de intestino delgado. Hasta el momento no hay acuerdo sobre cómo administrar la cápsula a los pacientes que han sido sometidos a una cirugía gastrointestinal previa. Objetivo: El objetivo principal fue comparar la tasa de estudios completos entre la ingestión oral y la administración endoscópica de la cápsula. Los objetivos secundarios fueron comparar el rendimiento diagnóstico y los eventos adversos en ambos grupos. Métodos: Se realizó un estudio observacional retrospectivo en 9 hospitales de España. Se recogieron datos demográficos, cirugía previa, indicación de cápsula endoscópica, tiempo de tránsito intestinal, diagnóstico, tasa de estudios completos (porcentaje de cápsulas que llegan al ciego), rendimiento diagnóstico (porcentaje de resultados compatibles con la indicación del examen) y eventos adversos. Resultados: Desde enero de 2009 hasta mayo de 2019 se incluyeron 57 pacientes (39 hombres, edad media 66 ± 15 años). Las indicaciones más frecuentes para el examen fueron hemorragia de intestino delgado «manifiesta» (50,9%) y «oculta» (35,1%). El 52,6% de los pacientes presentaba gastrectomía Billroth II y el 17,5% bypass gástrico en Y de Roux. La cápsula fue ingerida en 34 pacientes y colocada endoscópicamente en 23 pacientes. No se observaron diferencias significativas entre los grupos de ingesta oral y de colocación endoscópica en cuanto a tasa de estudios completos (82,4% vs. 78,3%; p = 0,742), rendimiento diagnóstico (41,2% vs. 52,2%; p = 0,432) y tiempo de tránsito del intestino delgado (301 vs. 377 min, p = 0,118). No hubo casos de cápsulas retenidas. Solo se observó un evento adverso severo (perforación anastomótica) en el grupo de colocación endoscópica...(AU)

Manejo de fracturas abiertas de tibia en Cuba / Management of Open Tibial Fractures in Cuba

Introducción: Las fracturas abiertas de tibia son un subconjunto de la carga de traumatismos en América Latina. Se examinaron cuestiones relacionadas con el tratamiento potencialmente críticas en Cuba, país con recursos limitados, pero con un programa nacional de salud estandarizado, coherencia en educación y similitudes de programas de posgrado. Objetivos: Describir los patrones de tratamiento de la fractura abierta de tibia en Cuba, y comparar las características del manejo agudo y tardío en siete provincias del país. Métodos: Se encuestaron 67 cirujanos ortopédicos para evaluar cuatro aspectos en el tratamiento de la fractura abierta: profilaxis antibiótica, irrigación y desbridamiento, estabilización y tratamiento de heridas. Se utilizó el método de muestreo por conveniencia para identificar a los cirujanos y el análisis se realizó mediante la prueba exacta de Fisher (p < 0,05). Resultados: Se administraron antibióticos posoperatorios durante más de 72 horas para las fracturas GA-I/II (49 por ciento) y las fracturas GA-III (70 por ciento). Los cirujanos de La Habana (n= 32) utilizaron con más frecuencia la fijación interna primaria para las fracturas GA-I/II, que los cirujanos en las restantes provincias (n= 35) (64,3 porciento vs. 30,3 por ciento, p= 0,008). Los cirujanos de otras provincias realizaron cierre primario en el momento de la fijación definitiva de fracturas GA-I /II con más frecuencia que los de La Habana (62,9 por ciento vs. 32,3 por ciento, p= 0,013). Para fracturas GA-III, la mayoría de los cirujanos habaneros (88,6 %), al igual que los de las restantes provincias (96,8 por ciento) prefirieron realizar cierre diferido.Conclusiones: El tratamiento de fracturas abiertas de tibia en Cuba es generalmente consistente con otros países de América Latina. Se describen las características del manejo de fracturas abiertas de tibia en Cuba y se comparan las diferencias en los métodos de estabilización y tratamiento de heridas entre provincias, lo cual resulta útil para evaluar si son resultado de diferencias en la práctica quirúrgica, o en la disponibilidad de recursos. Esto representa una ayuda al abordar las formas de optimizar la atención al paciente, a través de la capacitación especializada y la asignación de los recursos(AU)

Introduction: Open tibia fractures are a significant subset of the overall trauma burden in Latin America. Latin American countries vary in their access to orthopaedic care resources, and country-specific orthopaedic recommendations are necessary. Cuba, a country with limited resources, has a standardized national health program, consistencies in education, and similarities across post-graduate training programs. This study aimed to identify management preferences for open tibia factures in Cuba. Objectives: To describe the treatment of open tibial fractures in Cuba, and to compare the characteristics of acute and delayed management across seven Cuban provinces. Methods: Sixty-seven orthopaedic surgeons were surveyed to evaluate four aspects of open fracture management, regarding antibiotic prophylaxis, irrigation and debridement, stabilization, and wound management. The convenience sampling method was used to identify surgeons and the analysis was performed using Fisher's exact test (p <0.05). Results: Postoperative antibiotics were administered for more than 72 hours for GA-I / II fractures (49 pecent) and GA-III fractures (70 percent). Surgeons in Havana (n = 32) used primary internal fixation for GA-I / II fractures more frequently than surgeons in the remaining provinces (n = 35) (64.3 pecent vs. 30.3 percent p = 0.008). Surgeons from other provinces performed primary closure at the time of definitive fixation of GA-I / II fractures more frequently than those from Havana (62.9 percent vs. 32.3 percent, p = 0.013). For GA-III fractures, the majority of Havana surgeons (88.6 percent), as well as those of the remaining provinces (96.8 percent) preferred to perform deferred closure. Conclusions: The treatment of open tibial fractures in Cuba is generally consistent with other Latin American countries. The characteristics of the management of open tibial fractures in Cuba are described and differences in wound stabilization and treatment methods between provinces are compared, which is useful to assess whether they are the result of differences in surgical practice, or in availability of resources. This is helpful in addressing ways to optimize patient care through specialized training and resource allocation(AU)

Restauración de la biomecánica en artroplastia total de cadera por luxación congénita alta / Restoration of Biomechanics in Total Hip Arthroplasty Due to High Congenital Dislocation

La osteoartritis secundaria a displasia o luxación congénita de cadera conlleva grandes dificultades para el cirujano que reconstruye la cadera. Los casos con escasa deformidad no difieren prácticamente de la reconstrucción primaria convencional. En el extremo opuesto están los casos con graves hipoplasias del acetábulo, escaso desarrollo femoral, luxación completa, discrepancia importante de las extremidades y gran cabalgamiento del trocánter mayor. Por las enormes dificultades que pueden representar para la cirugía, nos trazamos el objetivo de discutir nuestro caso, con las consideraciones y resultados del tratamiento elegido. Se presenta paciente femenina de 54 años de edad, con antecedentes de salud previa, que nos llegó a consulta con una grave deformidad congénita, acortamiento del miembro inferior derecho (6 cm) y limitación dolorosa de todos los movimientos de la cadera. Se constata una luxación congénita grado C de Hartofilakidis y IV de Crowe, que muestra como parte del tratamiento, la artroplastia total con injerto autólogo y reimplantación del cótilo en el acetábulo verdadero, para recuperar el centro de rotación del acetábulo y la osteotomía femoral de acortamiento para la implantación del vástago femoral. Se exponen los requerimientos, procederes técnicos y resultados alcanzados(AU)

Osteoarthritis secondary to congenital hip dysplasia or dislocation poses great difficulties for the surgeon reconstructing the hip. Cases with little deformity do not differ practically from conventional primary reconstruction. At the opposite end there are cases with severe acetabulum hypoplasia, poor femoral development, complete dislocation, significant limb discrepancy, and great thrust of the greater trochanter. Due to the enormous difficulties that they can represent for surgery, we set the objective of discussing our case, with the considerations and results of the chosen treatment. A 54-year-old female patient is reported, she has previous health history, and she came for consultation with severe congenital deformity, shortening of her right lower limb (6 cm) and painful limitation of all hip movements. Congenital dislocation grade C of Hartofilakidis and IV of Crowe was confirmed, which showed as part of the treatment, the total arthroplasty with autologous graft and reimplantation of the cup in the true acetabulum, to recover the center of rotation of the acetabulum and the shortening femoral osteotomy for implantation of the femoral stem. Requirements, technical procedures and results achieved are informed(AU)

Componentes protésicos más usados en la artroplastia total de cadera en las provincias centrales / Most Used Prosthetic Components in Total Hip Arthroplasty in Central Provinces

Introducción: La cirugía de la artroplastia y el recambio de una prótesis de cadera es una cirugía compleja y costosa. La estrategia quirúrgica y componentes protésicos son completamente diferentes en función de las deformidades óseas existentes y características anatómicas personales de cada paciente, por tanto, la planificación de suministros de los diferentes componentes es básica para cubrir las demandas de la población necesitada y la adecuada eficiencia económica para evitar gastos innecesarios por sobreestimación o infraestimación de las demandas. Objetivos: Determinar las necesidades por medidas de los diferentes tipos de componentes protésicos utilizados en la artroplastia total de cadera en las provincias centrales y de este modo optimizar las inversiones, con las ventajas económicas que supone. Métodos: Estudio longitudinal descriptivo retrospectivo de los casos operados de artroplastia total de cadera en el Hospital Arnaldo Milián Castro de Villa Clara, desde diciembre de 1998 hasta la fecha. Se analizan las variables edad, sexo, procedencia y componentes protésicos. Se recoge la información en la base de datos creada en SPSS, donde se realizan los análisis estadísticos. Resultados: La edad media fue 62,36 años. El grupo de 61 - 80 años fue el de mayor incidencia con 215 pacientes. Predominó el sexo masculino 51,8 por ciento. La mayor incidencia, correspondió a Villa Clara con 692 pacientes. Los componentes cementados 46 - 50 fueron los más usados y en los no cementados los más usados fueron 48-56. Vástagos Tipo Müller 7.5 - 12.5. RALCA Cementadas T0-T4, no cementados T1-T3. En las SLA, 11.5 y 13. Los cuellos estándar fueron los de mayor incidencia con 390 pacientes. Conclusiones: Con las incidencias de las diferentes medidas utilizadas por cada uno de los componentes expresados, se puede determinar con bastante exactitud la demanda de cada medida por cada 100 casos pendientes de operación. Esto permite satisfacer las demandas de las medidas más usadas y hacer una distribución apropiada a la hora del suministro, lo que redundaría en un beneficio económico vital en las actuales condiciones del país(AU)

Introduction: The arthroplasty surgery and the replacement of a hip replacement is a complex and expensive surgery. The surgical strategy and prosthetic components are completely different depending on the existing bone deformities and personal anatomical characteristics of each patient, therefore, the planning of supplies of the different components is essential to meet the demands of the needy population and adequate economic efficiency to avoid unnecessary expenses due to overestimation or underestimation of claims. Objective: To determine the needs by measurements of the different types of prosthetic components used in total hip arthroplasty in the central provinces and thus optimize investments, with the economic advantages that it entails. Methods: A retrospective descriptive longitudinal study was carried out of the total hip arthroplasty operated cases at Arnaldo Milián Castro Hospital in Villa Clara, from December 1998 to date. Age, sex, origin and prosthetic components are the variables examined. The information is collected in the database created in SPSS, statistical analyzes was performed. Results: The mean age was 62.36 years. The group of 61-80 years was the one with the highest incidence (215 patients). Male sex predominated (51.8 percent). The highest incidence corresponded to Villa Clara (692 patients). The cemented components 46-50 were the most used and in the uncemented components the most used were 48-56. Müller Stems 7.5 - 12.5. RALCA Cemented T0-T4, uncemented T1-T3. In the SLA the most used were 11.5 and 13 respectively. Standard necks were those with the highest incidence (390 patients). Conclusions: The demand for each measure can be determined quite accurately for every 100 cases pending operation with the incidents of the different measures used by each of the components expressed, allowing to meet the demands of the most used measures and appropriate distribution at supplying, which would result in vital economic benefit in the current conditions of the country(AU)

Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality?

Background: The link between coagulation system disorders and COVID-19 has not yet been fully elucidated. Aim: Evaluating the association of non-previously reported coagulation proteins with COVID-19 severity and mortality. Design: Cross-sectional study of 134 COVID-19 patients recruited at admission and classified according to the highest COVID-19 severity reached (asymptomatic/mild, moderate, or severe) and 16 healthy control individuals. Methods: Coagulation proteins levels (antithrombin, prothrombin, factor_XI, factor_XII, and factor_XIII) and CRP were measured in plasma by the ProcartaPlex Panel (Invitrogen) multiplex immunoassay upon diagnosis. Results: We found higher levels of antithrombin, prothrombin, factor XI, factor XII, and factor XIII in asymptomatic/mild and moderate COVID-19 patients compared to healthy individuals. Interestingly, decreased levels of antithrombin and factors XI, XII, and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death. Conclusion: COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might "paradoxically" imply a higher risk of progression to severe disease and COVID-19-related mortality.

Human inbreeding has decreased in time through the Holocene.

The history of human inbreeding is controversial.1 In particular, how the development of sedentary and/or agricultural societies may have influenced overall inbreeding levels, relative to those of hunter-gatherer communities, is unclear.2-5 Here, we present an approach for reliable estimation of runs of homozygosity (ROHs) in genomes with ≥3× mean sequence coverage across >1 million SNPs and apply this to 411 ancient Eurasian genomes from the last 15,000 years.5-34 We show that the frequency of inbreeding, as measured by ROHs, has decreased over time. The strongest effect is associated with the Neolithic transition, but the trend has since continued, indicating a population size effect on inbreeding prevalence. We further show that most inbreeding in our historical sample can be attributed to small population size instead of consanguinity. Cases of high consanguinity were rare and only observed among members of farming societies in our sample. Despite the lack of evidence for common consanguinity in our ancient sample, consanguineous traditions are today prevalent in various modern-day Eurasian societies,1,35-37 suggesting that such practices may have become widespread within the last few millennia.