Hypertensive states of pregnancy.

Hypertensive disorders in pregnancy (HDP) remain a leading cause of pregnancy-related maternal and foetal morbidity and mortality worldwide, including chronic hypertension, gestational hypertension, and pre-eclampsia. Affected women and newborns also have an increased risk of cardiovascular disease later in life, independent of traditional cardiovascular disease risks. Despite these risks, recommendations for optimal diagnosis and treatment have changed little in recent decades, probably due to fear of the foetal repercussions of decreased blood pressure and possible drug toxicity. In this document we review the diagnostic criteria and classification of (HDP), as well as important aspects regarding pathophysiology and early detection that allows early identification of women at risk, with the aim of preventing both immediate and long-term consequences. Prophylactic treatment with aspirin is also reviewed early and a therapeutic approach is carried out that involves close maternal and foetal monitoring, and if necessary, the use of safe drugs in each situation. This review aims to provide an updated vision for the prevention, diagnosis, and treatment of HDP that is useful in our usual clinical practice.

Long-term efficacy of percutaneous tibial nerve stimulation for faecal incontinence and a new approach for partial responders.

BACKGROUND: The aim of the present study was to evaluate the long-term efficacy of percutaneous tibial nerve stimulation (PTNS) for patients with faecal incontinence (FI) refractory to conservative treatment. Secondary aims were to identify predictors of response and validate new treatment pathways for partial responders. METHODS: A prospective, interventional study was carried out in a specialist defecatory disorder unit from a university hospital between January 2010 and June 2017 on patients > 18 years old with FI refractory to conservative treatment. Thirty-minute PTNS sessions were performed in three phases (weekly, biweekly and monthly) up to a year, with clinical reassessment at 3, 6, 12 and 36 months. Patients were classified as optimal responders when their pretreatment Wexner score decreased > 50%; partial responders when it decreased 25-50%; and insufficient responders if it decreased < 25%. Only optimal and partial responders progressed into successive phases. RESULTS: Between 2010 and 2017, 139 patients (110 women, median age 63 years [range 22-82 years]) were recruited. After the first phase, 4 patients were optimal responders, 93 were partial responders and 36 were insufficient responders. At 6 and 12 months, 66 and 89 patients respectively were optimal responders, with an optimal response rate of 64% at the end of treatment. A total of 93.3% patients with a partial response initially finally became optimal responders. Furthermore, at 36 months, 71.9% of patients were still optimal responders without supplementary treatment, although their quality of life did not improve significantly. Baseline Wexner scores ≤ 10 and symptom duration < 1 year were identified as predictive factors for positive responses to PTNS. CONCLUSIONS: Patients undergoing PTNS for 1 year following this protocol had optimal long-term responses. PTNS sessions for up to 1 year in patients who were partial responders prevents a high percentage of them from needing more invasive treatments, and maintains long-term continence in patients who were optimal responders.

Ecosystem productivity affected the spatiotemporal disappearance of Neanderthals in Iberia.

What role did fluctuations play in biomass availability for secondary consumers in the disappearance of Neanderthals and the survival of modern humans? To answer this, we quantify the effects of stadial and interstadial conditions on ecosystem productivity and human spatiotemporal distribution patterns during the Middle to Upper Palaeolithic transition (50,000-30,000 calibrated years before the present) in Iberia. First, we used summed probability distribution, optimal linear estimation and Bayesian age modelling to reconstruct an updated timescale for the transition. Next, we executed a generalized dynamic vegetation model to estimate the net primary productivity. Finally, we developed a macroecological model validated with present-day observations to calculate herbivore abundance. The results indicate that, in the Eurosiberian region, the disappearance of Neanderthal groups was contemporaneous with a significant decrease in the available biomass for secondary consumers, and the arrival of the first Homo sapiens populations coincided with an increase in herbivore carrying capacity. During stadials, the Mediterranean region had the most stable conditions and the highest biomass of medium and medium-large herbivores. These outcomes support an ecological cause for the hiatus between the Mousterian and Aurignacian technocomplexes in Northern Iberia and the longer persistence of Neanderthals in southern latitudes.

Internet, video game and mobile phone addiction in children and adolescents diagnosed with ADHD: A case-control study. / Adicción a Internet, videojuegos y teléfonos móviles en niños y adolescentes: Un estudio de casos y controles.

The use of new technologies has become widespread worldwide. There is increasing concern about "Internet addiction disorder" (IAD), "Internet gaming disorder" (IGD), and "Mobile phone addiction" (MPA). Attention Deficit Hyperactivity Disorder (ADHD) has been associated with IAD and IGD. However, evidence is lacking about the relationship between ADHD and MPA. Naturalistic case-control study. 112 patients (51 children with and 61 children without ADHD) between 7 and 17 years old were compared regarding IAD, IGD, and MPA. We used the TEA questionnaire for the assessment of executive function and ADHD (ATENTO), and the ADITEC questionnaire to get gender-differentiated information for IAD, IGD, and MPA. Female children scored higher on MPA (Mean ± Standard Deviation, M ± SD) (25.93 ±  17.64 vs. 14.77 ±  19.43, p=0.03), while male children scored higher on IGD (30.09 ± 21.65 vs. 12.51 ± 16.61, p < 10^-3). Severity of hyperactivity/impulsivity and IGD were moderately correlated (r=0.349, p=0.013), but the correlation disappeared after controlling for the impact on the social domain as measured by the ATENTO questionnaire (r=171, p=0.250). Most parents are concerned that their children may be addicted to IAD/IGD/MPA. Female gender is associated with MPA, while male gender is associated with IGD. ADHD is a risk factor for developing IAD and IGD. Combined type and predominantly hyperactive/impulsive ADHD are each associated with IGD. Good social adjustment protects against developing IGD. There are gender vulnerabilities for IAD/IGD/MPA. ADHD is a risk factor for IGD, but good social adjustment buffers this association.

El uso de las nuevas tecnologías se ha generalizado a nivel mundial. Hay una creciente preocupación respecto del «trastorno de adicción a Internet¼ (TAI), el «trastorno de juego en Internet¼ (TJI) y la «adicción al teléfono móvil¼ (ATM). El trastorno por el déficit de atención con hiperactividad (TDAH) se ha asociado con el TAI y el TJI. Sin embargo, falta evidencia sobre la relación entre el TDAH y la ATM. Estudio naturalista de casos y controles. Comparación de 112 pacientes (51 niños con el TDAH y 61 niños sin el TDAH) con edades entre 7-17 años respecto del TAI, el TJI y la ATM. Utilizamos el cuestionario de TEA para evaluar la función ejecutiva y el TDAH (ATENTO) y el cuestionario ADITEC para obtener información diferenciada por género para el TAI, el TJI y la ATM. Las niñas obtuvieron puntuaciones más altas en la ATM (desviación típica ± media, DT ± M) (25,93 ± 17,64 vs. 14,77 ± 19,43, p = ,03), mientras que los niños obtuvieron puntuaciones más altas en el TJI (30,09 ± 21,65 vs. 12,51 ± 16,61, p < 10

Obstructed defaecation syndrome: European consensus guidelines on the surgical management.

Clinical decision-making in the treatment of patients with obstructed defaecation remains controversial and no international guidelines have been provided so far. This study reports a consensus among European opinion leaders on the management of obstructed defaecation in different possible clinical scenarios.

Determinants of survival after severe acute respiratory syndrome coronavirus 2 infection in Mexican outpatients and hospitalised patients.

OBJECTIVES: This study aimed to evaluate the association of chronic diseases and indigenous ethnicity on the poor prognosis of outpatients with coronavirus disease 2019 (COVID-19) and hospitalised patients in Mexico. STUDY DESIGN: The study design is an observational study of consecutive COVID-19 cases that were treated in Mexican healthcare units and hospitals between February 27 and April 27, 2020. METHODS: Epidemiological, clinical and sociodemographic data were analysed from outpatients and hospitalised patients. Cox regression models were used to analyse the risk of mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: In total, 15,529 patients with COVID-19 were characterised; 62.6% of patients were aged older than 40 years, 57.8% were men and 1.4% were of indigenous ethnicity. A high proportion had a history of diabetes (18.4%), hypertension (21.9%) and obesity (20.9%). Among hospitalised patients, 11.2% received health care in the intensive care unit. Advanced age, male sex, indigenous ethnicity and having a history of chronic diseases, such as hypertension, diabetes and obesity, were significantly associated with a high risk of death after SARS-CoV-2 infection. Diabetes and obesity were the comorbidities most highly associated with death through the models used in this study. Moreover, living in Mexico City and Mexico State (where there is easy access to medical services) and walking (rather than driving or getting public transport) were negatively associated with mortality after SARS-CoV-2 infection. CONCLUSIONS: Diabetes, hypertension and obesity combined with older age, male sex and indigenous ethnicity increase the risk of death after SARS-CoV-2 infection in the Mexican population. It is recommended that the incidence of COVID-19 is monitored in indigenous communities, and access to health services is increased nationwide.

Segregation of four Agrobacterium tumefaciens replicons during polar growth: PopZ and PodJ control segregation of essential replicons.

Agrobacterium tumefaciens C58 contains four replicons, circular chromosome (CC), linear chromosome (LC), cryptic plasmid (pAt), and tumor-inducing plasmid (pTi), and grows by polar growth from a single growth pole (GP), while the old cell compartment and its old pole (OP) do not elongate. We monitored the replication and segregation of these four genetic elements during polar growth. The three largest replicons (CC, LC, pAt) reside in the OP compartment prior to replication; post replication one copy migrates to the GP prior to division. CC resides at a fixed location at the OP and replicates first. LC does not stay fixed at the OP once the cell cycle begins and replicates from varied locations 20 min later than CC. pAt localizes similarly to LC prior to replication, but replicates before the LC and after the CC. pTi does not have a fixed location, and post replication it segregates randomly throughout old and new cell compartments, while undergoing one to three rounds of replication during a single cell cycle. Segregation of the CC and LC is dependent on the GP and OP identity factors PopZ and PodJ, respectively. Without PopZ, replicated CC and LC do not efficiently partition, resulting in sibling cells without CC or LC. Without PodJ, the CC and LC exhibit abnormal localization to the GP at the beginning of the cell cycle and replicate from this position. These data reveal PodJ plays an essential role in CC and LC tethering to the OP during early stages of polar growth.

Publisher Correction: Feasibility and effects of enhanced recovery vs. conventional care after emergency colon surgery for patients with left colon perforation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Feasibility and effects of enhanced recovery vs. conventional care after emergency colon surgery for patients with left colon perforation.

The impact of an enhanced recovery after surgery (ERAS) programme in emergency colorectal surgery has not yet been reported. The objective of this study was to evaluate the feasibility and the results of patients included in an ERAS protocol following emergency colon surgery for left colon perforation. For this purpose, patients with a low to moderate risk of mortality, according to a Peritonitis Severity Score (PSS), and treated with an ERAS protocol (ERAS group) after emergency surgery for left colon perforation were compared for a period of 40 months (March 2014-June 2017) with a control group of patients treated with conventional care (CC group) during the 38 months prior to implementation of the new ERAS protocol (January 2011-February 2014). The main endpoint was 90-day postoperative morbidity according to the Clavien-Dindo classification. Secondary endpoints included length of postoperative hospital stay, 90-day readmission rate, protocol compliance and mortality. Fifty patients were included in the study, 29 in the ERAS group and 21 in the CC group. There were no significant differences between the groups in the demographic data or in the operative characteristics. A reduction in the incidence of postoperative complications (20.7% vs. 38%; p > 0.05) and in the postoperative hospital stay (7.7 + /- 3.85 vs. 10.9 + /- 5.6 days; p = 0.009) were observed in the ERAS group. The 90-day readmission rate did not differ significantly between the two groups (2 vs. 1). No 90-day mortality was observed in either group. The ERAS group showed better results than the CC group in protocol compliance. We conclude that ERAS protocols are feasible and help to reduce morbidity and length of hospital stay without adversely affecting the rate of readmission or mortality.

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk.

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a-/- mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling.

Safety and Efficacy of Prolonged Use of Dalbavancin in Bone and Joint Infections.

Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included. Staphylococcus epidermidis and Staphylococcus aureus were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.

Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery.

BACKGROUND: Systemic inflammation is pivotal in the pathogenesis of cardiovascular disease. As inflammation can directly cause cardiomyocyte injury, we hypothesised that established systemic inflammation, as reflected by elevated preoperative neutrophil-lymphocyte ratio (NLR) >4, predisposes patients to perioperative myocardial injury. METHODS: We prospectively recruited 1652 patients aged ≥45 yr who underwent non-cardiac surgery in two UK centres. Serum high sensitivity troponin T (hsTnT) concentrations were measured on the first three postoperative days. Clinicians and investigators were blinded to the troponin results. The primary outcome was perioperative myocardial injury, defined as hsTnT≥14 ng L-1 within 3 days after surgery. We assessed whether myocardial injury was associated with preoperative NLR>4, activated reactive oxygen species (ROS) generation in circulating monocytes, or both. Multivariable logistic regression analysis explored associations between age, sex, NLR, Revised Cardiac Risk Index, individual leukocyte subsets, and myocardial injury. Flow cytometric quantification of ROS was done in 21 patients. Data are presented as n (%) or odds ratio (OR) with 95% confidence intervals. RESULTS: Preoperative NLR>4 was present in 239/1652 (14.5%) patients. Myocardial injury occurred in 405/1652 (24.5%) patients and was more common in patients with preoperative NLR>4 [OR: 2.56 (1.92-3.41); P<0.0001]. Myocardial injury was independently associated with lower absolute preoperative lymphocyte count [OR 1.80 (1.50-2.17); P<0.0001] and higher absolute preoperative monocyte count [OR 1.93 (1.12-3.30); P=0.017]. Monocyte ROS generation correlated with NLR (r=0.47; P=0.03). CONCLUSIONS: Preoperative NLR>4 is associated with perioperative myocardial injury, independent of conventional risk factors. Systemic inflammation may contribute to the development of perioperative myocardial injury. CLINICAL TRIAL REGISTRATION: NCT01842568.

Role of leucocyte caspase-1 activity in epidural-related maternal fever: a single-centre, observational, mechanistic cohort study.

BACKGROUND: Epidural-related maternal fever (ERMF) has been reported in ∼26% of labouring women. The underlying mechanisms remain unclear. We hypothesised that ERMF is promoted by bupivacaine disrupting cytokine production/release from mononuclear leucocytes [mononuclear fraction (MNF)]. We examined whether bupivacaine (i) reduces caspase-1 activity and release of the anti-pyrogenic cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), and (ii) is pro-inflammatory through mitochondrial injury/IL-1ß. METHODS: In labouring women, blood samples were obtained before/after epidural analgesia was implemented. Maternal temperature was recorded hourly for the first 4 h of epidural analgesia. Time-matched samples/temperatures were obtained from labouring women without epidural analgesia, pregnant non-labouring, and non-pregnant women. The primary clinical outcome was change in maternal temperature over 4 h after the onset of siting epidural catheter/enrolment. The secondary clinical outcome was development of ERMF (temperature ≥ 38°C). The effect of bupivacaine/saline on apoptosis, caspase-1 activity, intracellular IL-1ra, and plasma IL-1ra/IL-1ß ratio was quantified in MNF from labouring women or THP-1 monocytes (using flow cytometry, respirometry, or enzyme-linked immunosorbent assay). RESULTS: Maternal temperature increased by 0.06°C h-1 [95% confidence interval (CI): 0.03-0.09; P=0.003; n=38] after labour epidural placement. ERMF only occurred in women receiving epidural analgesia (five of 38; 13.2%). Bupivacaine did not alter MNF or THP-1 apoptosis compared with saline control, but reduced caspase-1 activity by 11% (95% CI: 5-17; n=10) in MNF from women in established labour. Bupivacaine increased intracellular MNF IL-1ra by 25% (95% CI: 10-41; P<0.001; n=10) compared with saline-control. Epidural analgesia reduced plasma IL-1ra/IL-1ß ratio (mean reduction: 14; 95% CI: 7-30; n=30) compared with women without epidural analgesia. CONCLUSIONS: Impaired release of anti-pyrogenic IL-1ra might explain ERMF mechanistically. Immunomodulation by bupivacaine during labour could promote ERMF.