Virtual Screening of Small Molecules Targeting BCL2 with Machine Learning, Molecular Docking, and MD Simulation.

This study aimed to identify potential BCL-2 small molecule inhibitors using deep neural networks (DNN) and random forest (RF), algorithms as well as molecular docking and molecular dynamics (MD) simulations to screen a library of small molecules. The RF model classified 61% (2355/3867) of molecules as 'Active'. Further analysis through molecular docking with Vina identified CHEMBL3940231, CHEMBL3938023, and CHEMBL3947358 as top-scored small molecules with docking scores of -11, -10.9, and 10.8 kcal/mol, respectively. MD simulations validated these compounds' stability and binding affinity to the BCL2 protein.

Low-Dose Gamma Radiation Sterilization for Decellularized Tracheal Grafts.

One of the main key aspects in ensuring that a transplant evolves correctly is the sterility of the medium. Decellularized tracheal transplantation involves implanting an organ that was originally in contact with the environment, thus not being sterile from the outset. While the decellularization protocol (through detergent exposition [2% sodium dodecyl sulfate], continuous stirring, and osmotic shocks) is conducted in line with aseptic measures, it does not provide sterilization. Therefore, one of the main challenges is ensuring sterility prior to in vivo implantation. Although there are established gamma radiation sterilization protocols for inorganic materials, there are no such measures for organic materials. Additionally, the protocols in place for inorganic materials cannot be applied to organic materials, as the established radiation dose (25 kGy) would completely destroy the implant. This paper studies the effect of an escalated radiation dose in a decellularized rabbit trachea. We maintained the dose range (kGy) and tested escalated doses until finding the minimal dose at which sterilization is achieved. After determining the dose, we studied effects of it on the organ, both histologically and biomechanically. We determined that while 0.5 kGy did not achieve sterility, doses of both 1 kGy and 2 kGy did, with 1 kGy, therefore, being the minimal dose necessary to achieve sterilization. Microscopic studies showed no relevant changes compared to non-sterilized organs. Axial biomechanical characteristics were not altered at all, and only a slight reduction in the force per unit of length that the organ can radially tolerate was observed. We can therefore conclude that 1 kGy achieves complete sterilization of decellularized rabbit trachea with a minimal, if any, effects on the organ.

Diagnostic accuracy of C-reactive protein, procalcitonin and neutrophils for the early detection of anastomotic leakage after colorectal resection: a multicentric, prospective study.

AIM: The aim was to determine the accuracy of C-reactive protein (CRP), procalcitonin and neutrophils in the early detection (fourth postoperative day) of anastomotic leakage (AL) after colorectal surgery. METHODS: We conducted a multicentre, prospective study that included a consecutive series of patients who underwent colorectal resection with anastomosis without ostomy (September 2015 to December 2017). CRP, procalcitonin and neutrophil values on the fourth postoperative day after colorectal resection along with the postoperative outcome (60-day AL, morbidity and mortality) were prospectively included in an online, anonymous database. RESULTS: The analysis ultimately included 2501 cases. The overall morbidity and mortality was 30.1% and 1.6%, respectively, and the AL rate was 8.6%. The area under the receiver operating characteristic curve values (95% CI) for detecting AL were 0.84 (0.81-0.87), 0.75 (0.72-0.79) and 0.70 (0.66-0.74) for CRP, procalcitonin and neutrophils, respectively. The best cut-off level for CRP was 119 mg/l, resulting in 70% sensitivity, 81% specificity and 97% negative predictive value. After laparoscopic resection, the accuracy for CRP and procalcitonin was increased, compared with open resection. The combination of two or three of these biomarkers did not significantly increase their accuracy. CONCLUSION: On the fourth postoperative day, CRP was the most reliable marker for excluding AL. Its high negative predictive value, especially after laparoscopic resection, allows for safe hospital discharge on the fourth postoperative day. The routine use of procalcitonin or neutrophil counts does not seem to increase the diagnostic accuracy.

Analysis of SNP Array Abnormalities in Patients with DE NOVO Acute Myeloid Leukemia with Normal Karyotype.

Nearly 50% of patients with de novo acute myeloid leukemia (AML) harbor an apparently normal karyotype (NK) by conventional cytogenetic techniques showing a very heterogeneous prognosis. This could be related to the presence of cryptic cytogenetic abnormalities (CCA) not detectable by conventional methods. The study of copy number alterations (CNA) and loss of heterozygozity (LOH) in hematological malignancies is possible using a high resolution SNP-array. Recently, in clinical practice the karyotype study has been complemented with the identification of point mutations in an increasing number of genes. We analyzed 252 de novo NK-AML patients from Hospital La Fe (n = 44) and from previously reported cohorts (n = 208) to identify CCA by SNP-array, and to integrate the analysis of CCA with molecular alterations detected by Next-Generation-sequencing. CCA were detected in 58% of patients. In addition, 49% of them harbored CNA or LOH and point mutations, simultaneously. Patients were grouped in 3 sets by their abnormalities: patients carrying several CCA simultaneously, patients with mutations in FLT3, NPM1 and/or DNMT3A and patients with an amalgam of mutations. We found a negative correlation between the number of CCA and the outcome of the patients. This study outlines that CCA are present in up to 50% of NK-AML patients and have a negative impact on the outcome. CCA may contribute to the heterogeneous prognosis.

Efficacy Study of Anti-Endomysium Antibodies for Celiac Disease Diagnosis: A Retrospective Study in a Spanish Pediatric Population.

The aim of this study was to assess the efficacy of anti-endomysium antibodies (EMA) as a serological marker for celiac disease (CD) diagnosis in a pediatric population. A retrospective study of pediatric patients who underwent a CD serological markers study: EMA and anti-tissue transglutaminase antibodies (anti-TG2). Clinical symptomatology, degree of histological lesion, human leukocyte antigen (HLA) haplotype compatible with CD (HLA DQ2 and/or DQ8), and final diagnosis were taken into account. We included 445 patients who were classified in two groups according to the final diagnosis. Group 1: 232 children with CD, 91.4% of whom exhibited small intestinal villous atrophy, 228 being EMA-positive and four EMA-negative. Group 2: 213 children with a non-CD diagnosis, 212 EMA negative and one EMA positive. Both antibodies, EMA and anti-TG2, reached similar sensitivities, 98% and 99% respectively, while EMA had a higher specificity (99%) than anti-TG2 (93%). By using both markers combined, compared to using anti-TG2 alone, 5.7% of patients are better diagnosed. However, when we compare the efficacy of EMA and anti-TG2 in asymptomatic and symptomatic patients, the sensitivity of EMA is 98% irrespective of symptoms, thus higher than for anti-TG2 ≥10 × upper limit of normal (ULN) (respectively 77% and 84%). Our results support the use of EMA to increase CD diagnostic accuracy in a non-biopsy approach, especially in asymptomatic children.

Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although most cSCCs have good prognosis, a subgroup of high-risk cSCC has a higher frequency of recurrence and mortality. Therefore, the identification of molecular risk factors associated with this aggressive subtype is of major interest. In this work we carried out a global-scale approach to investigate the DNA-methylation profile in patients at different stages, from premalignant actinic keratosis to low-risk invasive and high-risk non-metastatic and metastatic cSCC. The results showed massive non-sequential changes in DNA-methylome and identified a minimal methylation signature that discriminates between stages. Importantly, a direct comparison of low-risk and high-risk stages revealed epigenetic traits characteristic of high-risk tumours. Finally, a prognostic prediction model in cSCC patients identified a methylation signature able to predict the overall survival of patients. Thus, the analysis of DNA-methylation in cSCC revealed changes during the evolution of the disease through the different stages that can be of great value not only in the diagnosis but also in the prognosis of the disease.

Relationship between structural damage with loss of strength and functional disability in psoriatic arthritis patients.

BACKGROUND: Evaluate the relationship between structural damage assessed by radiography or ultrasonography in the hands of patients with psoriatic arthritis (PsA) with loss of strength together with functional disability. METHODS: A cross-sectional study was conducted in patients with PsA involving the hands. Erosions and loss of radiographic joint space were measured in the dominant hand using a modified Sharp van der Heijde method and an ultrasound assessment. Hand strength was assessed with a dynamometer and disability was assessed using the Health Assessment Questionnaire (HAQ). The statistical analysis was performed using multiple linear regression models. FINDINGS: 76 patients were included with a mean age of 57 ±â€¯9.9 years, with 56.6% women. A statistically significant relationship was found between presence of erosions and reduction in lateral (p = 0.027) and tip (p = 0.030) pinch strength in the hand. This was also the case for loss of joint space and reduction in lateral (p = 0.012) and tip (p = 0.006) pinch strength. There was an association between total ultrasound (US) alterations and reduction in lateral pinch strength (p = 0.03). An association was also observed between erosions, loss of joint space and total US alterations and disability measured by the HAQ (p < 0.001; <0.001; 0.012, respectively). HAQ scores were associated with a decrease in mean lateral (p < 0.001) and tip (p < 0.001) pinch strength. INTERPRETATION: In patients with PsA involving the hands, structural alterations of the dominant hand assessed by conventional x-ray and ultrasound are associated with loss of strength measured objectively with dynamometry and greater disability also studied subjectively using the HAQ.

Maternal telomere length is shorter in intrauterine growth restriction versus uncomplicated pregnancies, but not in the offspring or in IVF-conceived newborns.

RESEARCH QUESTION: The study aimed to determine whether IVF or intrauterine growth restriction (IUGR) result in short neonatal telomeres, which could explain the higher risk of cardiovascular and metabolic disease described in these populations. DESIGN: This was an observational, analytical, cross-sectional, prospective study with controls in a tertiary hospital. The main outcome was to determine the leukocyte telomere length in 126 newborns and their mothers (n = 109). Newborns were conceived spontaneously or by IVF, and uncomplicated and IUGR pregnancies were studied. Telomere lengths were measured using high-throughput telomere quantitative fluorescent in-situ hybridization. RESULTS: There was no difference in average telomere length between newborns conceived by IVF or those with IUGR and spontaneously conceived healthy newborns (P = 0.466 and P = 0.732, respectively); this remained after controlling for confounders (P = 0.218 and P = 0.991, respectively). Mothers of newborns with IUGR had a shorter average telomere length than women with uncomplicated pregnancies (P = 0.023), which was confirmed after controlling for age, body mass index and smoking habit (P = 0.034). CONCLUSIONS: The results support the safety of IVF and IUGR in terms of the postnatal health of the newborns. The shorter telomeres of IUGR mothers may represent a higher cardiovascular risk, which would have clinical implications under the stress of pregnancy in otherwise healthy adults.

[Clinical usefulness of the non-invasive functional study of the lower urinary tract voiding phase as a predictor of resolution after the first endoscopic treatment of vesico-ureteral reflux in children older than 3 years.] / Utilidad del estudio funcional no invasivo de la fase de vaciado del tracto urinario inferior como factor predictor de la resolución tras el primer tratamiento endoscópico del reflujo vesico-ureteral en niños mayores de 3 años.

OBJECTIVES: To determine the usefulnessof voiding diary (VD), uroflowmetry with electromyography(UF-EMG), bladder wall thickness (before micturition)(VWTUS) and residual urine (PVR) (ultrasound measure)in predicting the outcome of the first endoscopic treatment(1ENDT) of vesicoureteral reflux (VUR) in children> 3 years. METHODS: Cross-sectional ambispective study of 48children with vesicoureteral reflux. Those with previousendoscopic treatment, age or neurological abnormalities and a history of urethralor abdominal surgery were excluded. The outcomevariable was the correctness (by isotopic cystography)three months after 1ENDT. Univariate and multivariateanalyses were performed through a Multilayer Perceptronnetwork and a logistic regression model EmpiricalBayesian penalized type LASSO Elastic net. Diagnosticaccuracy were determined. RESULTS: Mean age of the sample was 6.8 +/- 2.28years. The rate of VUR correction after 1ENDT was 77%.The variables selected by both methods were: VD-retentionist(OR 3.90), high PVR (OR 2.69), high VWTUS (OR4.44). Normal UF-EMG was a preventive variable (OR0.38). Diagnostic accuracy (pSp=48.7%), UF+EMG (Se=27.3%(Se=72.7% (AUC=0.8 cut point 20 ml),VWTUS (Se=81.8% (AUC=0.8 cut point4.6 mm). There were no statistical differences betweenPVR and VWTUS. Combined use of UF+EMG+PVR(Se=90.9%in predicting the persistence of VUR after 1ENDT inchildren > 3 years. After screening with a VD, UF-EMG+ RPM combination could be useful to detect these patientsand propose a treatment that improves bladdervoiding function prior to surgery.

OBJETIVOS: Determinar la utilidad deldiario miccional (DIM), la flujometría asociada a laelectromiografía (UF-EMG) y los parámetros ecográficoscomo son el espesor de la pared vesical premiciconal(EPVECO) y el residuo postmiccional (RPM) en la prediccióndel resultado del primer tratamiento endoscópico(1TEND) del Reflujo Vesico-Ureteral (RVU) en niños > 3años.MATERIAL Y MÉTODOS: Estudio transversal ambispectivode 48 niños con RVU. Criterios de exclusión: 1TENDprevio, edad y cirugía uretral o abdominal previas. Variableresultado: corrección del RVU (cistografía isotópica realizadatres meses después del 1TEND). Se realizaronanálisis univariante y multivariante mediante una red perceptrón multicapa y un modelo de regresión logísticapenalizada tipo Empirical Bayesian LASSO Elastic net.Se consideraron significativas las variables elegidas porambos métodos estadísticos. Se estudió el rendimientodiagnóstico de las pruebas individuales y combinadas. RESULTADOS: Media de edad: 6,8 +/- 2,28 años.Tasa de corrección del RVU traspredictoras de la persistencia del RVU tras 1TENDseleccionadas por ambos métodos: DIM-hábito retencionista(OR 3,90), RPM elevado (OR 2,69), EPVECOaumentado (OR 4,44). La UF-EMG sin alteracionesen el trazado se comportó como variable preventiva(OR 0,38). Rendimiento diagnóstico (p(Se=98% (Se=27,3%RPM (Se=72,7% (AUC=0,8 punto decorte óptimo 20 ml), EPVECO (Se=81,8%(AUC=0,8 punto de corte óptimo 4,6 mm).No existierondiferencias entre el uso del RPM y el EPVECO(p>0,05). Uso conjunto de UF-EMG+RPM (Se=90,9%Es=92%) (pCONCLUSIONES: El estudio funcional no invasivo dela fase de vaciado es útil en la predicción de la persistenciade RVU tras el 1TEND en niños >3 años. Trasel cribado con un diario miccional, la UF-EMG+RPMpodrían ser útiles para detectar a estos pacientes y plantearun tratamiento que mejore el vaciado vesical previoa la cirugía.

Does Metabolic Surgery Lead to Diabetes Remission in Patients with BMI < 30 kg/m2?: a Meta-analysis.

BACKGROUND: Bariatric surgery has demonstrated to be effective in remission of type 2 diabetes in obese patients, but it is unclear in non-obese patients. The aim of this study is to investigate if metabolic surgery is effective in diabetes resolution in patients with BMI < 30 kg/m2. MATERIALS AND METHODS: A systematic review was performed and the content of the PubMed, Ovid, and the Cochrane Library databases covering the period January 2008 to April 2018 was searched. Studies with metabolic surgery performed in patients with type 2 diabetes, BMI < 30 kg/m2 and a follow-up ≥ 6 months were included. Type 2 diabetes remission rate and metabolic parameters changes were measured. A meta-analysis was conducted with the selected studies. RESULTS: Twenty-six studies were included in the meta-analysis (1105 patients). The mixed-effects meta-analysis model for overall diabetes remission rate produced an estimate of 43% (95% IC 34-53%, p < 0.001). Moderator effects of the variables race, preoperative HbA1c, BMI, months of follow-up, duration of diabetes, and age on diabetes remission were also assessed, with no significant effects being found in any of them. A reduction in BMI (- 3.57 kg/m2), fasting blood glucose (- 55.93 mg/dL) and HbA1c (- 2.08%) was observed after surgery. CONCLUSIONS: Metabolic surgery could be effective in remission of type 2 diabetes in BMI < 30 kg/m2 patients but randomized and long-term studies are necessary. The scientific community should agree in a single definition of type 2 diabetes remission, in order to know the real effect of metabolic surgery in this group of patients.

Immunohistochemical expression of Ki-67, Cyclin D1, p16INK4a, and Survivin as a predictive tool for recurrence and progression-free survival in papillary urothelial bladder cancer pTa / pT1 G2 (WHO 1973).

OBJECTIVES: To investigate the expression of several immunohistochemical (IHC) markers and their predictive ability for the recurrence-free and progression-free survival of papillary urothelial bladder cancer (UBC) pTa/pT1 G2 (WHO 1973) compared to classical anatomo-clinical variables using a multidimensional analysis. MATERIALS AND METHODS: A population-based cohort of 213 primary stage UBC (pTa/pT1) G2 (WHO 1973) was evaluated by classic anatomopathological variables and characterized by immunohistochemistry (23 IHC markers, representative of different oncogenic pathways). The most important variables as a predictor of recurrence-free and progression-free survival were selected using multidimensional statistical models, such as random survival forests and least absolute shrinkage and selection operator (. Recurrence and progression-free survival of the previously selected variables were also calculated. RESULTS: Mean follow-up was 58 ± 33.5 months. Recurrence and progression rates were 54.5% (n = 116) and 17,4% (n = 37), respectively. The most influential variables in the low recurrence-free survival were in order: number of resected tumors, high expression of Ki67 (>10%), Cyclin D1 (>10%), and low cytoplasmic staining of p16INK4a. Regarding low progression-free survival, the most important variables were Ki67 (>15%), multicentric tumor arrangement and Survivin nuclear expression (>20%). Kaplan-Meier and cox-regression model analyses showed that the variables selected by multidimensional models were able to discriminate the clinical outcome. CONCLUSIONS: Ki67 index is the most useful IHC marker, since it can improve the prediction of both recurrence and progression-free survival in papillary UBC pTa/pT1 G2 (WHO 1973). There are other markers, whose utility is specific to recurrence-free survival, such as Cyclin D1 and p16INK4a or in progression-free survival, such as Survivin.

Cardiovascular risk reduction over time in patients with diabetes or pre-diabetes undergoing bariatric surgery: data from a single-center retrospective observational study.

BACKGROUND: Bariatric surgery is effective in remission of obesity comorbidities. This study was aimed at comparing CVD risk between morbidly obese patients with type 2 diabetes and pre-diabetes before and after bariatric surgery as well as assessing comorbidities. METHODS: This is a retrospective observational study with 105 patients with type 2 diabetes (DMbaseline) and prediabetes (preDMbaseline) who underwent Roux-en-Y gastric bypass. Data were collected preoperative and then at 3,6,12,18,24,36,48, and 60 months after surgery. Anthropometric, cardiovascular and glycemic parameters were assessed. CVD risk was calculated using the Framingham Risk Score. RESULTS: Prior to surgery, 48 patients had type 2 diabetes, while 57 had pre-diabetes. Mean age was 48 (9.2) and mean BMI was 52 (7.4). 26.1% of patients had a high CVD risk. CVD risk decreased in patients with type 2 diabetes and prediabetes at month 12 after surgery compared to the baseline risk (p < 0.001). BMI, body fat percentage, fasting plasma glucose, HbA1c, c-peptide, HOMA-IR, LDL-c, systolic blood pressure, and diastolic blood pressure decreased during the first year after surgery. From the 12th month until the 60th, they showed a flat trend, or a very mild increase in some cases. 3.2% of patients maintained high CVD risk at 60 months. Type 2 diabetes remission was 92%. No patient of the preDMbaseline group developed type 2 diabetes. CONCLUSION: Bariatric surgery reduces CVD risk in type 2 diabetes and pre-diabetes. Given that patients with type 2 diabetes benefit the most, more studies are necessary to consider pre-diabetes as a criterion for metabolic surgery in patients with BMI ≥ 35 kg/m2.

Antiepileptic drug reduction and increased risk of stimulation-evoked focal to bilateral tonic-clonic seizure during cortical stimulation in patients with focal epilepsy.

INTRODUCTION: Stimulation-evoked focal to bilateral tonic-clonic seizure (FBTCS) can be a stressful and possibly harmful adverse event for patients during cortical stimulation (CS). We evaluated if drug load reduction of antiepileptic drugs (AEDs) during CS increases the risk of stimulation-evoked FBTCS. MATERIAL AND METHODS: In this retrospective cohort study, we searched our local database for patients with drug-resistant epilepsy who underwent invasive video-EEG monitoring and CS in the University Hospital la Fe Valencia from January 2006 to November 2016. The AED drug load was calculated with the defined daily dose. We applied a uni- and multivariate logistic regression model to estimate the risk of stimulation-evoked FBTCS and evaluate possible influencing factors. Furthermore, we compared patients whose AEDs were completely withdrawn with those whose AEDs were not. RESULTS: Fifty-eight patients met the inclusion criteria and were included in the analysis. Stimulating 3806 electrode contact pairs, 152 seizures were evoked in 28 patients (48.3%). Ten seizures (6.6%) in seven patients (12.1%) evolved to FBTCS. In the univariate and multivariate analysis, a 10% reduction in drug load was associated with an increase of the odds ratio (OR) of stimulation-evoked FBTCS by 1.9 (95%-CI 1.2, 4.0, p-value=0.04) and 1.9 (95%-CI 1.2, 4.6, p-value=0.04), respectively. In patients, whose AEDs were completely withdrawn the OR of FBTCS increased by 9.1 (95%CI 1.7, 69.9, p-value=0.01) compared with patients whose AEDs were not completely withdrawn. No other factor (implantation type, maximum stimulus intensity, number of stimulated contacts, history of FBTCS, age, gender, or epilepsy type) appears to have a significant effect on the risk of stimulation-evoked FBTCS. CONCLUSIONS: The overall risk of stimulation-evoked FBTCS during CS is relatively low. However, a stronger reduction and, especially, a complete withdrawal of AEDs are associated with an increased risk of stimulation-evoked FBTCS.

Psychiatric symptoms after temporal epilepsy surgery. A one-year follow-up study.

Psychiatric symptoms must be considered in patients with refractory temporal lobe epilepsy after epilepsy surgery. The main objectives of our study were to describe clinical and socio-demographical characteristics of a cohort of patients with pharmacoresistant temporal lobe epilepsy who underwent temporal lobe epilepsy surgery, and moreover, to evaluate possible risk factors for developing psychiatric symptoms. In order to achieve those goals, we conducted a prospective evaluation of psychopathology throughout the first year after surgery in a clinical sample of 72 patients, by means of three clinical rated measures; the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the Brief Psychiatric Rating Scale (BPRS). The psychopathological evaluations were performed by an experienced psychiatrist. A presurgical evaluation was done by a multidisciplinary team (that includes neurologist, psychiatrist, neurosurgeon, neurophysiologist, radiologists, and nuclear medicine specialist) in all patients. The decision to proceed to surgery was taken after a surgical meeting of all members of the Multidisciplinary Epilepsy Unit team. The psychiatrist conducted two postoperative assessments at 6months and 12months after surgery. The main finding was that past history of mental illness (patients who were receiving psychiatric treatment prior to the baseline evaluation) was a risk factor for anxiety, depression, and psychosis after temporal lobe epilepsy surgery.

Choroidal thickness and visual prognosis in type 1 lesion due to neovascular age-related macular degeneration.

PURPOSE: To evaluate the association between subfoveal choroidal thickness and the visual outcome in eyes with type 1 choroidal neovascularization (CNV) due to neovascular age-related macular degeneration (nAMD). METHODS: This was a retrospective, longitudinal, cross-sectional study including patients diagnosed with nAMD type 1 lesions managed with intravitreal injections of ranibizumab in a PRN strategy during 24 months. Retrospective chart review of patients with type 1 CNV recording the visual acuity, number of intravitreal injections, multimodal imaging data, and follow-up period was performed. Subfoveal choroidal thickness was measured using enhanced depth imaging scans obtained with spectral-domain optical coherence tomography. RESULTS: Twenty-five eyes of 21 patients were included. The mean baseline logMAR best-corrected visual acuity was 0.52 (+0.35) (median 0.5; range 0.1-1; interquartile range (IQR) 0.3-0.8) and improved to 0.39 (+0.39) (median 0.4; range 0.1-1; IQR 0.2-0.5) by the end of the follow-up (p = 0.038). Subfoveal choroidal thickness was 202.8 (+60.3) µm (median 218; range 81-285; IQR 146-258). Statistical mixed effects model demonstrated an association between rate of improvement of visual acuity with subfoveal choroidal thickness after 24 months (p<0.001) (95% confidence interval 0.0002-0.0001 logMAR month µm); higher thickness values were correlated with better visual acuity. CONCLUSIONS: Thicker subfoveal choroid was associated with better visual outcomes in patients with type 1 CNV due to nAMD following a strict PRN regimen with intravitreal ranibizumab at 24 months of follow-up.

The Maternal Cytokine and Chemokine Profile of Naturally Conceived Gestations Is Mainly Preserved during In Vitro Fertilization and Egg Donation Pregnancies.

This prospective longitudinal study aimed at comparing maternal immune response among naturally conceived (NC; n = 25), in vitro fertilization (IVF; n = 25), and egg donation (ED; n = 25) pregnancies. The main outcome measures were, firstly, to follow up plasma levels of interleukin (IL) 1 beta, IL2, IL4, IL5, IL6, IL8, IL10, IL17, interferon gamma, tumor necrosis factor-alpha (TNFα), transforming growth factor-beta (TGFß), regulated upon activation normal T-cell expressed and secreted (RANTES), stromal cell-derived factor 1 alpha (SDF1α), and decidual granulocyte-macrophage colony-stimulating factor (GM-CSF) during the three trimesters of pregnancy during the three trimesters of pregnancy; secondly, to evaluate if the cytokine and chemokine pattern of ED pregnant women differs from that of those with autologous oocytes and, thirdly, to assess if women with preeclampsia show different cytokine and chemokine profile throughout pregnancy versus women with uneventful pregnancies. Pregnant women in the three study groups displayed similar cytokine and chemokine pattern throughout pregnancy. The levels of all quantified cytokines and chemokines, except RANTES, TNFα, IL8, TGFß, and SDF1α, rose in the second trimester compared with the first, and these higher values remained in the third trimester. ED pregnancies showed lower SDF1α levels in the third trimester compared with NC and IVF pregnancies. Patients who developed preeclampsia displayed higher SDF1α plasma levels in the third trimester.