Perinatal outcomes in lesbian couples employing shared motherhood IVF compared with those performing artificial insemination with donor sperm.

STUDY QUESTION: In lesbian couples, is shared motherhood IVF (SMI) associated with an increase in perinatal complications compared with artificial insemination with donor sperm (AID)? SUMMARY ANSWER: Singleton pregnancies in SMI and AID had very similar outcomes, except for a non-significant increase in the rate of preeclampsia/hypertension (PE/HT) in SMI (recipient's age-adjusted odds ratio (OR) = 1.9, 95% CI = 0.7-5.2; P = 0.19), but twin SMI pregnancies had a much higher frequency of PE/HT than AID twins (recipient's age-adjusted OR = 21.7, 95% CI = 2.8-289.4; P = 0.01). WHAT IS KNOWN ALREADY: Oocyte donation (OD) pregnancies are associated with an increase in perinatal complications, in particular, preterm delivery and low birth weight, and PE/HT. However, it is unclear to what extent these complications are due to OD process or to the conditions why OD was performed, such as advanced age and underlying health conditions. Unfortunately, the literature concerning perinatal outcomes in SMI is scarce. STUDY DESIGN, SIZE, DURATION: Retrospective study involving 660 SMI cycles (299 pregnancies) and 4349 AID cycles (949 pregnancies) assisted over a 10-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: All cycles fulfilling the inclusion criteria performed in lesbian couples seeking fertility treatment in 17 Spanish clinics of the same group. Pregnancy rates of SMI and AID cycles were compared. Perinatal outcomes were compared: gestational length, newborn weight, preterm and low birth rates, PE/HT rates, cesarean section rates, perinatal mortality, and newborn malformations. MAIN RESULTS AND THE ROLE OF CHANCE: Pregnancy rates were higher in SMI than in AID (45.3% versus 21.8%, P < 0.001). There was a non-significant trend to higher multiple rate in AID (4.7% versus 8.5%, P = 0.08). In single pregnancies, there were no differences between SMI and AID in gestational age (278 days (268-285) versus 279 (272-284), P = 0.24), preterm rate (8.3% versus 7.3%, P = 0.80), preterm <28 weeks (0.6% versus 0.4%, P = 1.00), newborn weight (3195 g (2915-3620) versus 3270 g (2980-3600), P = 0.296), low birth rate (6.4% versus 6.4%, P = 1.00), extremely low birth weight (0.6% versus 0.5%, P = 1.00), and the distribution of newborns by weight groups. Cesarean section rate, newborn malformation rate, and perinatal mortality were also similar in SMI and AID. Additionally, there was non-significant trend in hypertensive disorders to an increase in PE/HT among SMI (recipient's age-adjusted OR = 1.9, 95% CI = 0.7-5.2). Overall, perinatal data are consistent with what is reported in the general population. In twin pregnancies, the aforementioned perinatal parameters were also very similar in SMI and AID. However, SMI twin pregnancies had a very high risk of PE/HT when compared with AID (recipient's age-adjusted OR = 21.7, 95% CI = 2.8-289.4, P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Our data regarding the pregnancy course were obtained from information registered in the delivery report as well as from what was reported by the patients themselves, so a certain degree of inaccuracy cannot be ruled out. Additionally, in some parameters, there was up to 10% of data missing. However, since the methodology of reporting was the same in SMI and AID groups, one should not expect a differential reporting bias. It cannot be ruled out that the risk of PE/HT in simple gestations would be significant in a larger study. Additionally, in the SMI group allocation to the transfer of 2 embryos was not randomized so some bias is possible. WIDER IMPLICATIONS OF THE FINDINGS: SMI, if single embryo transfer is performed, seems to be is a safe procedure. Double embryo transfer should not be performed in SMI. Our data suggest that the majority of complications in OD could be related more with recipient status than with OD itself, since with SMI (performed in women without fertility problems) the perinatal complications were much lower than usually described in OD. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Halo effect of a Mediterranean-lifestyle weight-loss intervention on untreated family members' weight and physical activity: a prospective study.

OBJECTIVES: Obesity is subject to strong family clustering. The relatives of participants in weight-loss interventions may also modify their lifestyle and lose weight. The aim of this study was to examine the presence and magnitude of a halo effect in untreated family members of participants enrolled in a randomized, multi-component, lifestyle intervention. METHODS: A total of 148 untreated adult family members of participants in an intensive weight-loss lifestyle intervention (the PREDIMED-Plus study) were included. Changes at 1 and 2 years in body weight, physical activity, and adherence to a traditional Mediterranean diet (MedDiet) were measured. Generalized linear mixed models were used to assess whether the change differed between family members of the intervention group compared to the control. RESULTS: Untreated family members from the intervention group displayed a greater weight loss than those from the control after 1 and 2 years: adjusted 2-year weight change difference between groups was -3.98 (SE 1.10) kg (p < 0.001). There was a halo effect with regard to adherence to the MedDiet at one year which was sustained at two years: 2-year adjusted difference in MedDiet score change +3.25 (SE 0.46) (p < 0.001). In contrast, no halo effect was observed with regard to physical activity, as the untreated family members did not substantially modify their physical activity levels in either group, and the adjusted difference at two years between the 2 groups was -272 (SE 624) METs.min/week (p = 0.665). CONCLUSIONS: In the first prospective study to assess the influence on untreated family members of a diet and physical activity weight-loss intervention, we found evidence of a halo effect in relatives on weight loss and improvement in adherence to a MedDiet, but not on physical activity. The expansion of MedDiet changes from individuals involved in a weight-loss intervention to their family members can be a facilitator for obesity prevention.

Abnormally High Ankle-Brachial Index is Associated with All-cause and Cardiovascular Mortality: The REGICOR Study.

INTRODUCTION: The clinical significance of a high ankle brachial index (ABI) and its relationship to cardiovascular disease (CVD) and mortality is controversial. The aim of this study was to estimate the association between abnormally high ABI ≥ 1.4 and coronary heart disease (CHD), cerebrovascular disease, and all-cause mortality in a Mediterranean population without CVD. METHODS: A prospective population based cohort study of 6352 subjects was followed up for a median 6.2 years. Subjects under 35 years, with a history of CVD or an ABI < 0.9 were excluded. All CHD events (angina, myocardial infarction, coronary revascularisation), cerebrovascular events (stroke, transient ischaemic attack), and all-cause mortality were recorded. RESULTS: A total of 5679 subjects fulfilled the inclusion criteria, of which 5517 (97.1%) had a normal ABI whereas 162 (2.9%) had an ABI ≥ 1.4. The profile of individuals with abnormally high ABI revealed as independent related factors age (OR = 1.0; p = .045), female sex (OR = 0.4; p < .01), diabetes (OR = 1.9; p = .02), and lower diastolic blood pressure (OR = 0.9; p < .001). During follow-up 309 (5.4%) participants presented with a CV event and 286 (5.0%) died. An ABI ≥ 1.4 was associated with a higher incidence of CV events in the univariate (HR = 1.7) but not in the multivariate survival Cox regression analysis. An ABI ≥ 1.4 was independently associated with all-cause mortality (HR = 2.0; IC 95% 1.32-2.92) and cardiovascular mortality (HR = 3.1; IC 95% 1.52-6.48). CONCLUSIONS: In subjects without CVD, those with abnormally high ABI do not have a greater CV event rate than those with a normal ABI. However, there seems to be a trend towards higher mortality risk, supporting the guidelines that consider this subgroup to be a high risk population.

Intravenous thrombolysis in ischemic stroke with unknown onset using CT perfusion.

BACKGROUND: Acute ischemic stroke patients with unclear onset time presenting >4.5 h from last-seen-normal (LSN) time are considered late patients and excluded from i.v. thrombolysis. We aimed to evaluate whether this subgroup of patients is different from patients presenting >4.5 h from a witnessed onset, in terms of eligibility and response to computed tomography perfusion (CTP)-guided i.v. thrombolysis. METHODS: We prospectively studied consecutive acute non-lacunar middle cerebral artery (MCA) ischemic stroke patients presenting >4.5 h from LSN. All patients underwent multimodal CT and were considered eligible for i.v. thrombolysis according to CTP criteria. Two patient groups were established based on the knowledge of the stroke onset time. We compared the proportion of candidates suitable for intravenous thrombolysis between both groups, and their outcome after thrombolytic therapy. RESULTS: Among 147 MCA ischemic stroke patients presenting >4.5 h from LSN, stroke onset was witnessed in 74 and unknown in 73. Thirty-seven (50%) patients in the first group and 32 (44%) in the second met CTP criteria for thrombolysis (P = 0.7). Baseline variables were comparable between both groups with the exception of age, which was higher in the unclear onset group. The rates of early neurological improvement (54.1% vs 46.9%), 2-h MCA recanalization (43.5% vs 37%), symptomatic hemorrhagic transformation (3% vs 0%) and good 3-month functional outcome (62.2% vs 56.3%) did not differ significantly between both groups. CONCLUSION: Delayed stroke patients with unknown onset time were no different than patients >4.5 h regarding eligibility and response to CTP-based i.v. thrombolysis.

Collateral circulation on perfusion-computed tomography-source images predicts the response to stroke intravenous thrombolysis.

BACKGROUND AND PURPOSE: Perfusion-computed tomography-source images (PCT-SI) may allow a dynamic assessment of leptomeningeal collateral arteries (LMC) filling and emptying in middle cerebral artery (MCA) ischaemic stroke. We described a regional LMC scale on PCT-SI and hypothesized that a higher collateral score would predict a better response to intravenous (iv) thrombolysis. METHODS: We studied consecutive ischaemic stroke patients with an acute MCA occlusion documented by transcranial Doppler/transcranial color-coded duplex, treated with iv thrombolysis who underwent PCT prior to treatment. Readers evaluated PCT-SI in a blinded fashion to assess LMC within the hypoperfused MCA territory. LMC scored as follows: 0, absence of vessels; 1, collateral supply filling ≤ 50%; 2, between> 50% and < 100%; 3, equal or more prominent when compared with the unaffected hemisphere. The scale was divided into good (scores 2-3) vs. poor (scores 0-1) collaterals. The predetermined primary end-point was a good 3-month functional outcome, while early neurological recovery, transcranial duplex-assessed 24-h MCA recanalization, 24-h hypodensity volume and hemorrhagic transformation were considered secondary end-points. RESULTS: Fifty-four patients were included (55.5% women, median NIHSS 10), and 4-13-23-14 patients had LMC score (LMCs) of 0-1-2-3, respectively. The probability of a good long-term outcome augmented gradually with increasing LMCs: (0) 0%; (1) 15.4%; (2) 65.2%; (3) 64.3%, P = 0.004. Good-LMCs was independently associated with a good outcome [OR 21.02 (95% CI 2.23-197.75), P = 0.008]. Patients with good LMCs had better early neurological recovery (P = 0.001), smaller hypodensity volumes (P < 0.001) and a clear trend towards a higher recanalization rate. CONCLUSIONS: A higher degree of LMC assessed by PCT-SI predicts good response to iv thrombolysis in MCA ischaemic stroke patients.

Real-life results in treating neovascular age-related macular degeneration with anti-VEGF therapy. Analysis of 122 patients from a single centre.

BACKGROUND: The prognosis of age-related macular degeneration (AMD) has improved significantly since the advent of antiangiogenic treatments. However, several «real life¼ studies have shown lower number of injections and a markedly worse visual prognosis than pivotal clinical trials. OBJECTIVE: To assess the effectiveness and safety of the treatment of neovascular AMD and analyse clinical factors related to the functional and structural prognosis in routine clinical practice. MATERIAL AND METHODS: Retrospective, observational, single-centre study that included 143 eyes of 122 patients diagnosed with neovascular AMD between the years 2015 and 2016, who received treatment with antiangiogenic drugs and were followed up for two or more years. RESULTS: Visual acuity improved in 45% of patients after two years of treatment. The mean decrease in central macular thickness was 85 µm (p < 0.001) and the mean number of injections was 13. Retinal pigment epithelium rupture was present in 3.5%. Ranibizumab was the drug most used as a first option, although 79 patients (55.2%) required a change in treatment, most being switched to aflibercept. A greater number of visits (p < 0.001) and a lower number of injections (p < 0.01) were predictors of worse structural outcome. The number of visits was associated with better visual acuity (p < 0.001). CONCLUSIONS: The treatment has demonstrated its efficacy by improving visual acuity and central macular thickness. However, the number of injections performed has generally been higher than in other real-life studies.

DNA methylation biomarkers of myocardial infarction and cardiovascular disease.

BACKGROUND: The epigenetic landscape underlying cardiovascular disease (CVD) is not completely understood and the clinical value of the identified biomarkers is still limited. We aimed to identify differentially methylated loci associated with acute myocardial infarction (AMI) and assess their validity as predictive and causal biomarkers. RESULTS: We designed a case-control, two-stage, epigenome-wide association study on AMI (ndiscovery = 391, nvalidation = 204). DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. We performed a fixed-effects meta-analysis of the two samples. 34 CpGs were associated with AMI. Only 12 of them were available in two independent cohort studies (n ~ 1800 and n ~ 2500) with incident coronary and cardiovascular disease (CHD and CVD, respectively). The Infinium HumanMethylation450 BeadChip was used in those two studies. Four of the 12 CpGs were validated in association with incident CHD: AHRR-mapping cg05575921, PTCD2-mapping cg25769469, intergenic cg21566642 and MPO-mapping cg04988978. We then assessed whether methylation risk scores based on those CpGs improved the predictive capacity of the Framingham risk function, but they did not. Finally, we aimed to study the causality of those associations using a Mendelian randomization approach but only one of the CpGs had a genetic influence and therefore the results were not conclusive. CONCLUSIONS: We have identified 34 CpGs related to AMI. These loci highlight the relevance of smoking, lipid metabolism, and inflammation in the biological mechanisms related to AMI. Four were additionally associated with incident CHD and CVD but did not provide additional predictive information.

The role of the p-value in the multitesting problem.

Modern science frequently involves the analysis of large amount of quantitative information and the simultaneous testing of thousands or even hundreds of thousands null hypotheses. In this context, sometimes, naive deductions derived from the statistical reports substitute the rational thinking. The reproducibility crisis is a direct consequence of the misleading statistical conclusions. In this paper, the authors revisit some of the controversies on the implications derived from the statistical hypothesis testing. They focus on the role of the p-value on the massive multitesting problem and the loss of its standard probabilistic interpretation. The analogy between the hypothesis tests and the usual diagnostic process (both involve a decision-making) is used to point out some limitations in the probabilistic p-value interpretation and to introduce the receiver-operating characteristic, ROC, curve as a useful tool in the large-scale multitesting context. The analysis of the well-known Hedenfalk data illustrates the problem.

Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats.

The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg) on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions.

[Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Contribution of two new cases]. / Síndrome "overlap" hepatitis autoinmune-cirrosis biliar primaria. Aportación de dos nuevos casos.

The autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome is characterized for clinical, biochemical, immunological, and histological features overlapping those of AIH and PBC, whose pathogenesis and more appropriate treatment are unknown at present. We describe two new patients of this entity, which made debut with cholestasic acute hepatitis accompanied of hypergammaglobulinemia. In the first patient was demonstrated the presence of AMA, ASMA, and anti-LKM1 autoantibodies; and ANA in the second one. The histological findings showed changes suggestive of AIH and PBC. After the start of immunosuppressive treatment, associated to ursodeoxycholic acid in one patient, a successful outcome was observed.

[Carpal tunnel syndrome: clinical and neurophysiological correlation: review of 100 cases]. / Síndrome del túnel del carpo. Correlación clínica y neurofisiológica: revisión de 100 casos.

INTRODUCTION: The diagnosis of carpal tunnel syndrome (CTS) continues to be neurophysiologically and clinically controversial. This study attempts to find the correlation between the subjective symptomatology and the neurophysiological affectation, establishing a diagnostic guide for the family doctor in order to recognize early CTS for referral to the specialist doctor. PATIENTS AND METHODS: After a sample of 100 cases with clinical suspicion of CTS, a clinical evaluation was made with the symptoms (paresthesias, pain, loss of strength), signs (Tinel, Phalen), and the neurophysiological evaluation with electroneurography (ENG) of the median and cubital nerve (sensory velocity (SV), motor distal latency (MDL)), and electromyography (EMG) of tenar eminence muscles. With this data an epidemiological study was made with correlation between the clinical and neurophysiological parameters. RESULTS: The patients with pain, loss of strength and Tinel's sign had significant alteration of the parameters of ENG and EMG. Tinel's sign had a sensitivity (SE) = 30.1% and a specificity (SP) = 73% for MDL, a SE = 32.5% and a SP = 88.2% for SV. Phalen's sign had a SE = 22.2% and a SP = 94.6% for MDL, a SE = 18.1% and a SP = 94.1% for SV. CONCLUSIONS: The guide to recognize clinically the patients which must be studied neurophysiologically that have a high probability to suffer CTS is: diagnosis for motor alteration, pain (SE = 79%), loss of strength (SP = 86%) and Phalen's sign (SP = 94.6%). Sensory alteration: paresthesias (SE = 97%), Tinel's sign (SP = 88.2%) and Phalen's sign (SP = 94.1%).

[Perfusion computed tomography makes it possible to overcome important SITS-MOST exclusion criteria for the endovenous thrombolysis of cerebral infarction]. / La tomografia computarizada de perfusion permite superar importantes criterios de exclusion SITS-MOST para la trombolisis endovenosa del infarto cerebral.

AIM. To study the frequency, safety and efficacy of perfusion computed tomography (PCT), through identification of brain tissue-at-risk, to guide intravenous thrombolysis in stroke patients with regulatory exclusion criteria (SITS-MOST and ECASS-3). PATIENTS AND METHODS. We studied consecutive acute non-lacunar ischemic stroke patients. After conventional CT was considered eligible, PCT was performed in the following circumstances: 4.5 to 6 h window, wake-up stroke or unknown time of onset; extent early infarct signs on CT; minor or severe stroke; seizures or loss of consciousness. Intravenous 0.9 mg/kg alteplase was indicated if: cerebral blood volume lesion covered < 1/3 of middle cerebral artery territory; mismatch > 20% between mean transit time and cerebral blood volume maps existed; and informed consent. SITS-MOST safety-efficacy parameters were used as endpoint variables. RESULTS. Between May 2009-April 2010, 66 hyperacute ischemic stroke patients a priori not eligible for intravenous thrombolysis underwent PCT. Indications were: > 4.5 h in 18 patients, wake up stroke or unknown onset in 25, extent infarct signs in 6, seizures at onset in 11, and minor stroke (NIHSS < 4) in 6. Twenty-nine (44%) of them finally received intravenous thrombolysis. Symptomatic hemorrhagic transformation occurred in 2 (6.9%) patient and 18 (62.1%) achieved a modified Rankin scale score equal or less than 2 on day 90. CONCLUSION. A high proportion of acute stroke patients with SITS-MOST and ECASS-3 exclusion criteria can be safely and efficaciously treated with intravenous thrombolysis using a PCT selection protocol. However randomized control trials will be needed to confirm our results.

[Reference values of T-lymphocyte subsets in umbilical cord blood]. / Valores de referencia de las subpoblaciones de linfocitos T en la sangre del cordón umbilical.

In order to determine reference values of T lymphocyte subpopulations in cord blood in the metropolitan area of Puebla city we randomly selected 80 from a total of 400 term, eutrofic and without pathology newborn. The percentage of CD3, CD4 and CD8 T lymphocyte subpopulations in cord blood were determined by flow cytometry. Reference values were gotten from the 25 and 75 percentile in parameters without gaussian distribution. Reference values are CD3 (45.5 to 91.3%), CD4 (26.2 to 69.4%), CD8 (16.2 to 24.1%) and NK (2.0 to 8.5%). The presented data represent valuable normal ranges of T lymphocyte subsets to compare with values observed in sick or in risk of developing immunoallergic pathology children.

[Enterococcus faecalis bacteremia]. / Bacteriemia por Enterococcus faecalis.

OBJECTIVE: Analysis of Enterococcus faecalis bacteremia epidemiological, clinical, microbiological and prognostic characteristics. METHODS: Retrospective analysis of clinical records of patients with E. faecalis bacteremia throughout 7 years (January 1995-December 2001). RESULTS: 95 episodes of bacteremia were documented, 83.2% with nosocomial origin, 85.3% associated to previous invasive procedures and 9.5% in neonates. 57.9% patients suffered an underlying disease and 41.1% had received previously broad-spectrum antibiotics without activity against enterococcus. 32.6% bacteremia episodes was considered primary and, in the rest, the most frequent associated sources of infection were cardiovascular, intra-abdominal, urogenital, and lung. The resistance study showed a single case of resistance to ampicillin and none to glucopeptides. Global mortality was 23.9%, although only in 9.9% was directly attributable to bacteremia. Inadecuate treatment and mechanical ventilation were factors of poor prognosis in the multivariate analysis. CONCLUSIONS: E. faecalis bacteremia is in our environment essentially a hospital-acquired infection in patients with severe underlying diseases, subject to invasive procedures, and previously treated with wide spectrum antibiotherapy. Ampicillin continues to be the treatment of choice. Inappropriateness of the initial empirical antibiotic treatment and mechanical ventilation are factors of poor prognosis.