The paradoxes of Mycobacterium tuberculosis molecular evolution and consequences for the inference of tuberculosis emergence date.

The date of Mycobacterium tuberculosis complex emergence has been the subject of long debates. New studies joining archaeological efforts with sequencing methods raise high hopes for solving whether this emergence is closer to 70,000 or to 6000 years before present. Inferring the date of emergence of this pathogen based on sequence data requires a molecular clock. Several clocks inferred from different types of loci and/or different samples, using both sound reasoning and reliable data, are actually very different, which we refer to as the paradoxes of M. tuberculosis molecular evolution. After having presented these paradoxes, we will remind the limits of the molecular clocks used in the different studies such as the assumption of homogeneous substitution rate. We will then review recent results that shed new light on the characteristics of M. tuberculosis molecular evolution: traces of diverse selection pressures, the impact of host dynamics, etc. We provide some ideas on what to do next to get nearer to a reliable dating of Mycobacterium tuberculosis complex emergence. Among them, the collection of additional remains from ancient tuberculosis seems still essential.

Independent inter and intra-observer agreement of the Schizas's classification of degenerative lumbar stenosis: Comparison among three levels of surgical training. / [Artículo traducido] Acuerdo inter- e intraobservador independiente de la clasificación de Schizas de estenosis lumbar degenerativa. Comparación entre tres niveles de entrenamiento quirúrgico.

INTRODUCTION AND OBJECTIVES: Lumbar spinal stenosis is a common age-related condition that affects the quality of life. Multiple classifications have been developed to quantify the severity of stenosis affecting comparison between studies and homogenous communication among surgeons and researchers. Even though this classification has not shown a direct clinical correlation, Schizas's classification appears to be a simple method to assess stenosis. Our objective was to evaluate the inter and intraobserver independent agreement of the Schizas's classification to assess stenosis severity. Additionally, we aimed to compare agreement among three levels of training in spine surgery. MATERIALS AND METHODS: An independent inter and intra observer agreement was conducted among junior, senior orthopedic residents and attending spine surgeons. Ninety lumbar levels from 30 patients were evaluated by 16 observers. Weighted kappa agreement was used. RESULTS: Overall interobserver and intraobserver agreement was of 0.57 (95% CI=0.52-0.63) and 0.69 (0.55-0.79), respectively. Interobserver agreement according to level of training yielded values of 0.53 (0.46-0.60) for junior residents, 0.61 (0.54-0.67) for senior residents and 0.67 (0.59-0.74) for attendings. Intraobserver agreement was of 0.54 (0.48-0.60) for junior, 0.60 (0.55-0.66) for senior and 0.66 (0.60-0.72) for attendings. CONCLUSION: The Schizas's classification showed moderate interobserver and substantial intraobserver agreement. Among attending surgeons, substantial inter and intraobserver agreement was observed. The classification allowed acceptable communication among trained spine surgeons.

Independent inter and intra-observer agreement of the Schizas's classification of degenerative lumbar stenosis: Comparison among three levels of surgical training.

INTRODUCTION AND OBJECTIVES: Lumbar spinal stenosis is a common age-related condition that affects the quality of life. Multiple classifications have been developed to quantify the severity of stenosis affecting comparison between studies and homogenous communication among surgeons and researchers. Even though this classification has not shown a direct clinical correlation, Schizas's classification appears to be a simple method to assess stenosis. Our objective was to evaluate the inter and intraobserver independent agreement of the Schizas's classification to assess stenosis severity. Additionally, we aimed to compare agreement among three levels of training in spine surgery. MATERIALS AND METHODS: An independent inter and intra observer agreement was conducted among junior, senior orthopedic residents and attending spine surgeons. Ninety lumbar levels from 30 patients were evaluated by 16 observers. Weighted kappa agreement was used. RESULTS: Overall interobserver and intraobserver agreement was of 0.57 (95% CI=0.52-0.63) and 0.69 (0.55-0.79), respectively. Interobserver agreement according to level of training yielded values of 0.53 (0.46-0.60) for junior residents, 0.61 (0.54-0.67) for senior residents and 0.67 (0.59-0.74) for attendings. Intraobserver agreement was of 0.54 (0.48-0.60) for junior, 0.60 (0.55-0.66) for senior and 0.66 (0.60-0.72) for attendings. CONCLUSION: The Schizas's classification showed moderate interobserver and substantial intraobserver agreement. Among attending surgeons, substantial inter and intraobserver agreement was observed. The classification allowed acceptable communication among trained spine surgeons.

Wound-related complications in the surgical treatment of vertebral metastatic disease - A case series analysis. / [Artículo traducido] Complicaciones relacionadas con la herida en el tratamiento quirúrgico de la enfermedad metastásica vertebral: análisis de una serie de casos.

INTRODUCTION AND OBJECTIVES: Spinal metastases (SM) account for 5-30% of patients with cancer, causing pain, deformity and/or neurological deficit. Postoperative complications are a concerning subject and wound-related complications (WRC) may delay adjuvant treatment. The objective of this study was to analyze the incidence of WRC in patients with SM that underwent surgical treatment as well as possible risk factors related to the occurrence of complications. MATERIALS AND METHODS: Patients with SM operated between 2011 and 2021 were analyzed. Demographics characteristics, primary tumor, general and neurological status, Tokuhashi score, type of surgical treatment, surgical length, preoperative serum albumin and hemoglobin, pre and postoperative adjuvant treatment were analyzed. The incidence and risk factors of WRC -surgical site infection, hematoma, and/or dehiscence- at 90 days was evaluated. Patients were classified in two groups according to the absence/presence of WRC. RESULTS: 198 patients (121 males and 77 females) with an average age of 65 years (range 54-73 years) were analyzed. WRC were observed in 44 patients (22%). On multivariable analysis, significant predictors for developing WRC were low Tokuhashi score (OR=7.89, 95% CI=1.37-45.35, p=.021), prostate cancer as primary tumor (6.73, 1.14-39.65, p=.035), and preoperative serum albumin level ≤3.5g/dL (2.31, 1.02-5.22, p=.044). There was no difference between groups on 90 days survival rate (p=.714). CONCLUSIONS: In our series, the incidence of WRC was 22%, main risk factors for complications were low Tokuhashi score, lower preoperative serum albumin, and prostate cancer. Finally, short-term survival rate was not affected by the occurrence of WRC.

Could thymoglobulin increase hemorrhagic risk in the perioperative transplantation period of sensitized kidney recipients?

OBJECTIVE: It has been described that thymoglobulin could increase the risk of infections and malignancies, in comparison to basiliximab. Leukopenia and thrombocytopenia are also more common within the first days after transplantation among thymoglobulin patients. Our objective was to analyze bleeding complications in this subset of patients. MATERIAL AND METHODS: Bleeding complications were evaluated among 515 renal transplants carried out at our institution between 2012 and 2018. We compared patients treated with thymoglobulin (Group 1, N=91) with those treated with basiliximab (Group 2, N=424). RESULTS: We found differences in platelet decrease: 95,142.2 (55,339.6) in Group 1 and 52,364.3 (69,116.6) in Group 2 (P=0.001), number of patients with severe thrombocytopenia (<75,000/mm3) (20.8% vs. 3.7%, P=0.001), number of blood units transfused (3.25 (0.572) vs. 2.2 (0.191, P=0.028) and percentage of patients that required surgery due to bleeding (18.2% vs. 7.7%, P=0.046). In a multiple lineal regression multivariable analysis (dependent variable was number of blood units transfused), only age [OR 0.037, 95% CI (0.003-0.070)] and type of immunosuppression [OR 1.592, 95% CI (1.38-2.84)] showed statistical significance. CONCLUSIONS: The use of thymoglobulin in the perioperative transplantation period could increase bleeding complications. In our series, in the group of patients with thymoglobulin, severe thrombocytopenia was 6 times more frequent, and active bleeding that required surgery was also 2.5 times more frequent. One way to continue with the use of this immunosuppression agent, might be to adjust the dose instead of discontinuing it. The use of thymoglobulin should be a factor to consider in the postoperative period of these patients.

Wound-related complications in the surgical treatment of vertebral metastatic disease - A case series analysis.

INTRODUCTION AND OBJECTIVES: Spinal metastases (SM) account for 5-30% of patients with cancer, causing pain, deformity and/or neurological deficit. Postoperative complications are a concerning subject and wound-related complications (WRC) may delay adjuvant treatment. The objective of this study was to analyze the incidence of WRC in patients with SM that underwent surgical treatment as well as possible risk factors related to the occurrence of complications. MATERIALS AND METHODS: Patients with SM operated between 2011 and 2021 were analyzed. Demographics characteristics, primary tumor, general and neurological status, Tokuhashi score, type of surgical treatment, surgical length, preoperative serum albumin and hemoglobin, pre and postoperative adjuvant treatment were analyzed. The incidence and risk factors of WRC - surgical site infection, hematoma, and/or dehiscence - at 90 days was evaluated. Patients were classified in two groups according to the absence/presence of WRC. RESULTS: 198 patients (121 males and 77 females) with an average age of 65 years (range 54-73 years) were analyzed. WRC were observed in 44 patients (22%). On multivariable analysis, significant predictors for developing WRC were low Tokuhashi score (OR=7.89, 95% CI=1.37-45.35, p=0.021), prostate cancer as primary tumor (6.73, 1.14-39.65, p=0.035), and preoperative serum albumin level ≤3.5g/dL (2.31, 1.02-5.22, p=0.044). There was no difference between groups on 90 days survival rate (p=0.714). CONCLUSIONS: In our series, the incidence of WRC was 22%, main risk factors for complications were low Tokuhashi score, lower preoperative serum albumin, and prostate cancer. Finally, short-term survival rate was not affected by the occurrence of WRC.

[Descriptive analysis of the electroencephalogram in Angelman syndrome]. / Análisis descriptivo del electroencefalograma en el síndrome de Angelman.

INTRODUCTION: Angelman syndrome is a neurodevelopmental disorder of genetic origin, with important clinical motor, behavioural, communicative and electroencephalographic manifestations, with particular relevance as regards the presence of epileptic seizures. AIMS: To describe the electroencephalographic characteristics (qualitatively and quantitatively) of patients diagnosed with Angelman syndrome and to determine the electroencephalographic profile according to age and genetic alteration. PATIENTS AND METHODS: A retrospective observational study in which the demographic, clinical and electroencephalographic characteristics of 51 patients with Angelman syndrome were analysed. RESULTS: A higher delta power was evident in all brain regions, with a maximum peak in the frontopolar and temporal regions, and a lower power in the alpha and beta frequency range in all regions, with a greater preponderance in younger patients, and a trend that decreases with age. The coherence showed a predominance of delta and theta in the frontopolar region, which was higher for all frequencies in the deletion group, where delta was predominant, especially in the frontopolar region. CONCLUSION: The electroencephalogram could be a useful biomarker as a qualitative and quantitative tool in the investigation of Angelman syndrome and in measuring the response to possible therapies under investigation.

TITLE: Análisis descriptivo del electroencefalograma en el síndrome de Angelman.Introducción. El síndrome de Angelman es un trastorno del neurodesarrollo de origen genético, con importantes manifestaciones clínicas motoras, conductuales, comunicativas y electroencefalográficas, con especial relevancia en lo que concierne a la presencia de crisis epilépticas. Objetivos. Describir las características electroencefalográficas (cualitativa y cuantitativamente) de los pacientes con diagnóstico de síndrome de Angelman y determinar el perfil electroencefalográfico según la edad y la alteración genética. Pacientes y métodos. Estudio observacional retrospectivo donde se analizaron las características demográficas, clínicas y electroencefalográficas de 51 pacientes con síndrome de Angelman. Resultados. Se evidenció una mayor potencia delta en todas las regiones cerebrales, con un pico máximo en las regiones frontopolar y temporal, y una menor potencia en el rango de frecuencias alfa y beta en todas las regiones, con mayor preponderancia en los pacientes más jóvenes, con tendencia decreciente con la edad. La coherencia mostró un predominio delta y theta en la región frontopolar, que fue mayor para todas las frecuencias en el grupo de deleción, con predominio delta, especialmente en la región frontopolar. Conclusión. El electroencefalograma podría ser un biomarcador útil como herramienta cualitativa y cuantitativa en la investigación del síndrome de Angelman y en la medición de la respuesta a eventuales terapias en investigación.

Tuberculosis trends in a hot-spot region in Paris, France.

SETTING: Tuberculosis (TB) incidence is declining overall in France, but not in Paris where some areas remain relative hot spots for TB.OBJECTIVES: To obtain a better knowledge of local TB epidemiology in order to facilitate control measures.DESIGN: Analysis of demographic data of TB patients diagnosed at the Bichat-Claude Bernard Hospital from 2007 to 2016, with spoligotyping of Mycobacterium tuberculosis complex isolates.RESULTS: During the study period, 1096 TB patients were analysed. The incidence of TB diagnosis was stable, averaging 115 patients per year, predominantly males (71%), foreign-born (81%), with pulmonary TB (77%) and negative HIV serology (88%). The mean age of foreign-born TB patients decreased over the study period, most significantly in recent arrivals in France, whose average age decreased by two years (P = 0.001). The time period between arrival in France and being diagnosed with active TB decreased annually significantly by 0.75 years (P = 0.02). The proportion of L4.6.2/Cameroon and L2/Beijing sub-lineages increased annually by 0.7% (P < 0.05). Multi-drug resistant strains, representing 4% of all strains, increased annually by 0.75% (P = 0.03)CONCLUSION: The number of TB patients remained high in northern Paris and the surrounding suburbs, suggesting the need for increased control measures.

Successful Allogenic Stem Cell Transplantation in Patients with Inherited CARD9 Deficiency.

Autosomal recessive (AR) CARD9 (caspase recruitment domain-containing protein 9) deficiency underlies invasive infections by fungi of the ascomycete phylum in previously healthy individuals at almost any age. Although CARD9 is expressed mostly by myeloid cells, the cellular basis of fungal infections in patients with inherited CARD9 deficiency is unclear. Therapy for fungal infections is challenging, with at least 20% premature mortality. We report two unrelated patients from Brazil and Morocco with AR CARD9 deficiency, both successfully treated with hematopoietic stem cell transplantation (HSCT). From childhood onward, the patients had invasive dermatophytic disease, which persisted or recurred despite multiple courses of antifungal treatment. Sanger sequencing identified homozygous missense CARD9 variants at the same residue, c.302G>T (p.R101L) in the Brazilian patient and c.301C>T (p.R101C) in the Moroccan patient. At the ages of 25 and 44 years, respectively, they received a HSCT. The first patient received a HLA-matched HSCT from his CARD9-mutated heterozygous sister. There was 100% donor chimerism at D + 100. The other patient received a T cell-depleted haploidentical HSCT from his CARD9-mutated heterozygous brother. A second HSCT from the same donor was performed due to severe amegakaryocytic thrombocytopenia despite achieving full donor chimerism (100%). At last follow-up, more than 3 years after HSCT, both patients have achieved complete clinical remission and stopped antifungal therapy. HSCT might be a life-saving therapeutic option in patients with AR CARD9 deficiency. This observation strongly suggests that the pathogenesis of fungal infections in these patients is largely due to the disruption of leukocyte-mediated CARD9 immunity.

Genomic characterization of MDR/XDR-TB in Kazakhstan by a combination of high-throughput methods predominantly shows the ongoing transmission of L2/Beijing 94-32 central Asian/Russian clusters.

BACKGROUND: Kazakhstan remains a high-burden TB prevalence country with a concomitent high-burden of multi-drug resistant tuberculosis. For this reason, we performed an in depth genetic diversity and population structure characterization of Mycobacterium tuberculosis complex (MTC) genetic diversity in Kazakhstan with both patient and community benefit. METHODS: A convenience sample of 700 MTC DNA cultures extracts from 630 tuberculosis patients recruited from 12 out of 14 regions in Kazakhstan, between 2010 and 2015, was independently studied by high-throughput hybridization-based methods, TB-SPRINT (59-Plex, n = 700), TB-SNPID (50-Plex, n = 543). DNA from 391 clinical isolates was successfully typed by two methods. To resolve the population structure of drug-resistant clades in more detail two complementary assays were run on the L2 isolates: an IS6110-NTF insertion site typing assay and a SigE SNP polymorphism assay. RESULTS: Strains belonged to L2/Beijing and L4/Euro-American sublineages; L2/Beijing prevalence totaled almost 80%. 50% of all samples were resistant to RIF and to INH., Subtyping showed that: (1) all L2/Beijing were "modern" Beijing and (2) most of these belonged to the previously described 94-32 sublineage (Central Asian/Russian), (3) at least two populations of the Central Asian/Russian sublineages are circulating in Kazakhstan, with different evolutionary dynamics. CONCLUSIONS: For the first time, the global genetic diversity and population structure of M. tuberculosis genotypes circulating in Kazakhstan was obtained and compared to previous local studies. Results suggest a region-specific spread of a very limited number of L2/Beijing clonal complexes in Kazakhstan many strongly associated with an MDR phenotype.

Another coin bites the dust: an analysis of dust in UTXO-based cryptocurrencies.

Unspent Transaction Outputs (UTXOs) are the internal mechanism used in many cryptocurrencies to represent coins. Such representation has some clear benefits, but also entails some complexities that, if not properly handled, may leave the system in an inefficient state. Specifically, inefficiencies arise when wallets (the software responsible for transferring coins between parties) do not manage UTXOs properly when performing payments. In this paper, we study three cryptocurrencies: Bitcoin, Bitcoin Cash and Litecoin, by analysing the state of their UTXO sets, that is, the status of their sets of spendable coins. These three cryptocurrencies are the top-3 UTXO-based cryptocurrencies by market capitalization. Our analysis shows that the usage of each cryptocurrency presents some differences, and led to different results. Furthermore, it also points out that the management of the transactions has not always been performed efficiently and therefore, the current state of the UTXO sets is far from ideal.

[Knowledge about Biosimilars in Primary Care: a study by the Spanish Society of Primary Care Physicians (SEMERGEN)]. / Conocimiento sobre biosimilares en Atención Primaria: Un estudio de la Sociedad Española de Médicos de Atención Primaria (SEMERGEN).

INTRODUCTION: The objective of this study was to evaluate the awareness and training needs on biosimilar drugs in Primary Care (PC) physicians. MATERIAL AND METHODS: Descriptive cross-sectional study based on an on-line questionnaire with a total of 34 multiple choice questions, published on the SEMERGEN website. The main Knowledge areas were: biosimilar definition; regulatory and legal framework; prescription, traceability, interchangeability and pharmacovigilance; availability of biosimilars in the PC setting, and the biosimilars contribution to sustainability. The software used for the analysis and data processing was the Barbwin 7.5. RESULTS: An analysis was performed on the responses from 701 questionnaires completed. There was a slight majority (57%) of women participants. The majority of participant worked in urban centres (60.91%). The definition of biosimilar was not known by 58% of those that responded, and 73% were unaware that the management of biosimilars and generics was not comparable. Most (84%) of those that responded were not aware that the studies required for the approval of biosimilars is different from reference biological medicines. Around two-thirds (66%) those that responded did not know of any biosimilars available in PC setting, and the 94% were also unaware of the Spanish legal framework for the management of biosimilar medicines. CONCLUSIONS: The current knowledge about biosimilars among PC physicians is low. The critical areas in need of further training include specific information on biosimilars currently available in PC setting, as well as key aspects regarding prescription, interchangeability and pharmacovigilance requirements. Six out of ten doctors do not know of any biosimilar used in PC in Spain.

Predictors and consequences of health anxiety symptoms: a novel twin modeling study.

OBJECTIVE: The question of how to best conceptualize health anxiety (HA) from a diagnostic and etiological perspective remains debated. The aim was to examine the relationship between HA and the symptoms of anxiety and obsessive-compulsive-related disorders in a normative twin population. METHOD: Four hundred and ninety-six monozygotic adult twin pairs from the Australian Twin Registry participated in the study (age, 34.4 ± 7.72 years; 59% females). Validated scales were used to assess each domain. We applied a twin regression methodology-ICE FALCON-to determine whether there was evidence consistent with 'causal' relationships between HA and other symptoms by fitting and comparing model estimates. RESULTS: Estimates were consistent with higher levels of obsessing ('unwanted thoughts') (P = 0.008), social anxiety (P = 0.03), and body dysmorphic symptoms (P = 0.008) causing higher levels of HA symptoms, and with higher levels of HA symptoms causing higher levels of physical/somatic anxiety symptoms (P = 0.001). CONCLUSION: Obsessional thoughts, body dysmorphic concerns, and social anxiety symptoms may have a causal influence on HA. To report physical/somatic anxiety appears to be a consequence of the underlying presence of HA-related fears. Should our results be confirmed by longitudinal studies, the evaluation and treatment of HA may benefit from the consideration of these identified risk factors.

Spinal anaesthesia in neonates and infants: what about the cerebral oxygen saturation?

BACKGROUND: Spinal Anaesthesia (SA) has been firmly established as an efficient and safe technique, with minimal cardio-respiratory disturbance when administered in the neonatal period. Our objective was to assess the haemodynamic consequences of SA in infants, particularly its impact on cerebral perfusion using near-infrared spectroscopy (NIRS)-based cerebral oximetry (rSco2). METHODS: All infants up to 60 weeks' postmenstrual age, whether formerly preterm or not, and undergoing spinal anaesthesia, were enrolled. Haemodynamic data records, rSco2 and mean arterial blood pressure (MAP), were prospectively collected before SA (T0) and every five min for 30 min (T30) after the puncture. Compared with baseline measures, any changes of > 10% in rSco2 and of > 20% in MAP were considered clinically significant. Relative variations of data between T0 and T30 were analysed. RESULTS: Data of 103 infants were analysed. The mean relative changes in rSco2 were -2.25% (97.5% CI [-3.97; -0.5]) at T15, and 0.11% (97.5% CI [-1.67; 1.90]) at T30. No significant variation of rSco2 was recorded. The mean changes in MAP were respectively -13.94% (97.5% CI [-17.74; -10.14]) at T15 and -20.27% (97.5% CI [-24,25; -16.29]) at T30. MAP decrease was statistically and clinically significant 30 min after SA. No correlation between changes in MAP and rSco2 was found. The subgroup analysis did not reveal any effect of added intrathecal clonidine or preterm birth history on these results. CONCLUSIONS: In neonate and infants, SA did not cause clinically significant variation in cerebral oxygen saturation. Despite a significant decrease in MAP, cerebral auto-regulation seems to remain effective in neonates and not altered by spinal anaesthesia.

Factors associated with lumbar disc hernia recurrence after microdiscectomy. / Factores asociados a recidiva de hernia de disco lumbar luego de una microdiscectomía.

INTRODUCTION: Lumbar disc hernias are a common cause of spinal surgery. Hernia recurrence is a prevalent complication. OBJECTIVE: To analyse the risk factors associated with hernia recurrence in patients undergoing surgery in our institution. MATERIALS AND METHODS: Lumbar microdiscectomies between 2010 and 2014 were analysed, patients with previous surgeries, extraforaminales and foraminal hernias were excluded. Patients with recurrent hernia were the case group and those who showed no recurrence were the control group. RESULTS: 177 patients with lumbar microdiscectomy, of whom 30 experienced recurrence (16%), and of these 27 were reoperated. Among the risk factors associated with recurrence, we observed a higher rate of disc height, higher percentage of spinal canal occupied by the hernia and presence of degenerative facet joint changes; we observed no differences in sex, body mass index or age. DISCUSSION: Previous studies show increased disc height and young patients as possible factors associated with recurrence. CONCLUSION: In our series we found that the higher rate of disc height, the percentage of spinal canal occupied by the hernia and degenerative facet joint changes were associated with hernia recurrence.

The effects of stress-tension on depression and anxiety symptoms: evidence from a novel twin modelling analysis.

BACKGROUND: Negative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs. METHOD: A total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress-tension. We applied a recently developed twin regression methodology - Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) - to test for evidence consistent with the existence of 'causal' influences between the DASS factors. RESULTS: There was evidence consistent with the stress-tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001). CONCLUSIONS: Our findings suggest a critical role for stress-tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms.

Cerebrospinal fluid volume in neonates undergoing spinal anaesthesia: a descriptive magnetic resonance imaging study.

BACKGROUND: Spinal anaesthesia (SA) reduces the risk of postoperative apnoea after general anaesthesia in neonates. In 30% of patients, however, the duration of anaesthesia provided does not allow completion of surgery. When compared with term infants, formerly preterm neonates experience a shorter duration of anaesthesia after SA. A difference in the cerebrospinal fluid (CSF) volume between those two populations could explain this difference, but this has never been investigated. The study was designed to evaluate the relationship between the spinal CSF volume and patient characteristics in neonates. METHODS: Sixty-seven neonates, aged 30-60 weeks postconception, were included in this study. Their spinal CSF volumes were calculated using magnetic resonance imaging, and these volumes were plotted individually against sex, term at birth, birth weight, current gestational age, civil age, and weight. Correlations between CSF volume and these variables were investigated. RESULTS: Fifty-four neonates completed the study. The CSF volume was found to be closely and linearly correlated with weight and postconceptional age. The relationship between spinal CSF volume and weight can be described as follows: CSF volume (ml)=1.94 weight (kg)+0.13. The CSF volume was not correlated with sex, weight, or term at birth, nor with civil age. CONCLUSIONS: The amount of spinal CSF in neonates can be estimated as 2 ml kg(-1) in both term and formerly preterm neonates. A difference in the CSF volume between them does not provide an explanation for a shorter duration of SA in the latter. Our findings reinforce weight-adjusted dosage of SA in neonates.

Clinical considerations on the posology of direct oral anticoagulants. / Consideraciones clínicas sobre la posología de los anticoagulantes orales de acción directa.

The efficacy of dicoumarin anticoagulants has been shown in patients with nonvalvular atrial fibrillation. However, they have drawbacks such as the need to adjust the dosage and the interaction with drugs and food. Direct oral anticoagulants are an effective and safe alternative and have a less complicated clinical management. There is considerable debate on the selection criteria for the posology regimens of direct oral anticoagulants. The differences among them and their administration regimens have raised questions about the clinical, pharmacokinetic and pharmacodynamic selection criteria that support the posology. This review critically analyses the available evidence and its impact on the final selection of the dosage regimen.

Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia.

Common single-nucleotide polymorphisms (SNPs) account for a large proportion of the heritability of obsessive-compulsive disorder (OCD). Co-ocurrence of OCD and schizophrenia is commoner than expected based on their respective prevalences, complicating the clinical management of patients. This study addresses two main objectives: to identify particular genes associated with OCD by SNP-based and gene-based tests; and to test the existence of a polygenic risk shared with schizophrenia. The primary analysis was an exon-focused genome-wide association study of 370 OCD cases and 443 controls from Spain. A polygenic risk model based on the Psychiatric Genetics Consortium schizophrenia data set (PGC-SCZ2) was tested in our OCD data. A polygenic risk model based on our OCD data was tested on previous data of schizophrenia from our group. The most significant association at the gene-based test was found at DNM3 (P=7.9 × 10(-5)), a gene involved in synaptic vesicle endocytosis. The polygenic risk model from PGC-SCZ2 data was strongly associated with disease status in our OCD sample, reaching its most significant value after removal of the major histocompatibility complex region (lowest P=2.3 × 10(-6), explaining 3.7% of the variance). The shared polygenic risk was confirmed in our schizophrenia data. In conclusion, DNM3 may be involved in risk to OCD. The shared polygenic risk between schizophrenia and OCD may be partially responsible for the frequent comorbidity of both disorders, explaining epidemiological data on cross-disorder risk. This common etiology may have clinical implications.