Duration of biophysical profile in periviable and very preterm low-risk pregnancies.

BACKGROUND: In recent years, perinatal viability has shifted from 24 to 22 weeks of gestation at many institutions after improvements in survival in neonates delivered at the limit of viability. Monitoring these fetuses is essential because antenatal interventions with resuscitation efforts are available for patients at risk of delivery at the limit of viability. However, fetal monitoring using biophysical profiles has not been extensively studied in very preterm pregnancies, particularly in the periviable period (20 weeks 0 days to 23 weeks 6 days). OBJECTIVE: This study aimed to (1) investigate whether the completion of biophysical profiles within 30 minutes is feasible in very preterm pregnancies, and (2) determine the average observation time required to achieve a score of 8 out of 8 in very preterm pregnancies from 20 weeks 0 days to 31 weeks 6 days. STUDY DESIGN: This study prospectively evaluated biophysical scores in singleton pregnancies undergoing routine ultrasonography at or near viability from 20 weeks 0 days to 23 weeks 6 days (periviable or group I), 24 weeks 0 days to 27 weeks 6 days (group II), and 28 weeks 0 days to 31 weeks 6 days (group III). The results and duration of biophysical profiles were compared with those of a control group (32 weeks 0 days to 35 weeks 6 days) undergoing indicated fetal surveillance. Biophysical profiles were performed for all studied pregnancies until a score of 8 out of 8 was obtained. When >1 biophysical profile was obtained during pregnancy, each was analyzed individually. Pregnancies with fetal anomalies or obstetrical/medical indications for fetal well-being surveillance were excluded. Analysis of variance and post hoc Tukey tests were used for comparisons. RESULTS: Data were collected for 123 participants, yielding 79, 75, and 72 studies for groups I, II, and III, respectively. The control group included 42 patients, yielding 140 studies. At 30 minutes, 80% (63/79) of the studies in the periviable group had a score of 8 out of 8, as opposed to 100% (140/140) in the control group (P<.001). The mean±standard deviation time in minutes to achieve a biophysical score of 8 out of 8 was 23.3±10.1 in the periviable group, as opposed to 9.4±6.5 in controls (P<.001). Extending the study to +2 standard deviations (43.6 minutes) in the periviable group resulted in 97% (77/79) of the scans scoring 8 out of 8 in the absence of adverse outcomes. In the other groups, a biophysical score of 8 out of 8 within 30 minutes was obtained in 97% (73/75) and 100% (72/72) in groups II and III, respectively; the mean±standard deviation times were 17.1±8.4 minutes (group II) and 13.1±7.3 minutes (group III). No adverse outcomes developed during the study participation in groups I to III. CONCLUSION: Biophysical scores of 8 out of 8 can be successfully achieved in low-risk periviable pregnancies (20 weeks 0 days to 23 weeks 6 days) within an observation time longer than the standard 30-minute duration. The time required to reach a score of 8 out of 8 decreases as gestation progresses. We suggest adjusting the observation time for biophysical profile completion according to the gestational age.

Development of a liver graft assessment expert machine-learning system: when the artificial intelligence helps liver transplant surgeons.

Background: The complex process of liver graft assessment is one point for improvement in liver transplantation. The main objective of this study is to develop a tool that supports the surgeon who is responsible for liver donation in the decision-making process whether to accept a graft or not using the initial variables available to it. Material and method: Liver graft samples candidate for liver transplantation after donor brain death were studied. All of them were evaluated "in situ" for transplantation, and those discarded after the "in situ" evaluation were considered as no transplantable liver grafts, while those grafts transplanted after "in situ" evaluation were considered as transplantable liver grafts. First, a single-center, retrospective and cohort study identifying the risk factors associated with the no transplantable group was performed. Then, a prediction model decision support system based on machine learning, and using a tree ensemble boosting classifier that is capable of helping to decide whether to accept or decline a donor liver graft, was developed. Results: A total of 350 liver grafts that were evaluated for liver transplantation were studied. Steatosis was the most frequent reason for classifying grafts as no transplantable, and the main risk factors identified in the univariant study were age, dyslipidemia, personal medical history, personal surgical history, bilirubinemia, and the result of previous liver ultrasound (p < 0.05). When studying the developed model, we observe that the best performance reordering in terms of accuracy corresponds to 76.29% with an area under the curve of 0.79. Furthermore, the model provides a classification together with a confidence index of reliability, for most cases in our data, with the probability of success in the prediction being above 0.85. Conclusion: The tool presented in this study obtains a high accuracy in predicting whether a liver graft will be transplanted or deemed non-transplantable based on the initial variables assigned to it. The inherent capacity for improvement in the system causes the rate of correct predictions to increase as new data are entered. Therefore, we believe it is a tool that can help optimize the graft pool for liver transplantation.

Predicting adverse outcomes in pregnant patients positive for SARS-CoV-2: a machine learning approach- a retrospective cohort study.

BACKGROUND: Pregnant people are particularly vulnerable to SARS-CoV-2 infection and to ensuing severe illness. Predicting adverse maternal and perinatal outcomes could aid clinicians in deciding on hospital admission and early initiation of treatment in affected individuals, streamlining the triaging processes. METHODS: An international repository of 1501 SARS-CoV-2-positive cases in pregnancy was created, consisting of demographic variables, patient comorbidities, laboratory markers, respiratory parameters, and COVID-19-related symptoms. Data were filtered, preprocessed, and feature selection methods were used to obtain the optimal feature subset for training a variety of machine learning models to predict maternal or fetal/neonatal death or critical illness. RESULTS: The Random Forest model demonstrated the best performance among the trained models, correctly identifying 83.3% of the high-risk patients and 92.5% of the low-risk patients, with an overall accuracy of 89.0%, an AUC of 0.90 (95% Confidence Interval 0.83 to 0.95), and a recall, precision, and F1 score of 0.85, 0.94, and 0.89, respectively. This was achieved using a feature subset of 25 features containing patient characteristics, symptoms, clinical signs, and laboratory markers. These included maternal BMI, gravidity, parity, existence of pre-existing conditions, nicotine exposure, anti-hypertensive medication administration, fetal malformations, antenatal corticosteroid administration, presence of dyspnea, sore throat, fever, fatigue, duration of symptom phase, existence of COVID-19-related pneumonia, need for maternal oxygen administration, disease-related inpatient treatment, and lab markers including sFLT-1/PlGF ratio, platelet count, and LDH. CONCLUSIONS: We present the first COVID-19 prognostication pipeline specifically for pregnant patients while utilizing a large SARS-CoV-2 in pregnancy data repository. Our model accurately identifies those at risk of severe illness or clinical deterioration, presenting a promising tool for advancing personalized medicine in pregnant patients with COVID-19.

Outcomes in Pregnant Adolescent Patients Infected With SARS-CoV-2.

BACKGROUND: Pregnant patients with coronavirus disease 2019 (COVID-19) are at risk for adverse pregnancy outcomes. Although clinical outcomes for pregnant adults have been reported, the impact of COVID-19 on adolescents is lacking. We sought to evaluate obstetric outcomes of pregnant adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and compare them with uninfected adolescent controls. METHODS: Retrospective cohort study of pregnant adolescents (14-19 years) who had a positive polymerase chain reaction test for SARS-CoV-2 from April 2020 to December 2020 at Inova Health System Hospitals. Controls included pregnant adolescents who tested negative. The primary outcome was a composite of preeclampsia, preterm delivery, cesarean delivery, fetal growth restriction and stillbirth. Secondary outcomes included maternal and neonatal morbidity. RESULTS: Forty-eight pregnant adolescents who tested positive for SARS-CoV-2 were compared with 394 controls. Infected adolescents were more likely to be Hispanic (91.67% vs. 12.18%; risk ratio [RR] 41.85 [95% CI: 15.43-113.5]) and uninsured (50% vs. 7.87%; RR 7.04 [95% CI: 4.31-11.49]. Nearly 80% of infected adolescents remained asymptomatic, whereas one-third of symptomatic adolescents progressed to severe or critical COVID-19. The primary composite outcome was more prevalent in infected adolescents compared with noninfected controls (41.67% vs. 25.38%; adjusted RR 2.65 [95% CI: 1.19-5.93]). Maternal morbidity was more prevalent in infected adolescents (6.25% vs. 0.76%; adjusted RR 9.53 [95% CI: 3.83-23.71]). Primary and secondary maternal outcomes were more prevalent in younger adolescents and those with higher severity of COVID-19. Maternal SARS-CoV-2 infection was not associated with neonatal morbidity. CONCLUSIONS: Pregnant adolescents infected with SARS-CoV-2 are more likely to have adverse obstetric outcomes and maternal morbidity compared with noninfected pregnant adolescents.

Efficacy of percutaneous pedicle screws for thoracic and lumbar spine fractures compared with open technique.

BACKGROUND: The objective of this study is to compare percutaneous techniques (MIS) with the open technique in terms of angle correction, long-term maintenance and clinical results. METHODS: The authors collected a prospective database of thoraco-lumbar fractures treated with posterior stabilization without fusion from 2013 to 2019. The statistical analysis has been carried out retrospectively. The patients were classified into Open and MIS group. To compare the two population, samples, treatments and mitigate the differences between the groups, the propensity score (PS) matching was used. RESULTS: One hundred and eight patients with thoraco-lumbar fractures were included. After performing the PS, 21 patients were obtained in the open group and 28 in the MIS group. For operative and perioperative parameters there were no differences in number of patients with posterior decompression, number of instrumented segments, number of total screws, operative time and complications. Postoperative hemoglobin was similar in both groups. However, in the open group a greater loss of hemoglobin was observed; as well as, higher analgesia requirements and length of stay. No statistically significant differences were observed in neurological status in both groups in the preoperative, postoperative period and at follow-up. The Cobb angle showed no differences at admission comparing both groups. A similar angle correction was observed with both surgeries, but in open surgery there was a statistically significant loss of correction. CONCLUSIONS: We observed in this study that the MIS technique for the treatment of thoracolumbar fractures is as effective as the open technique in terms of angle correction; and demonstrated that is better in its maintenance over time. Clinical results were at least as good as with the open technique.

Evaluation of first trimester ultrasound fetal biometry ratios femur length/biparietal diameter, femur length/abdominal circumference and femur length/foot for the screening of skeletal dysplasia.

OBJECTIVE: Skeletal dysplasia is usually apparent in the second trimester. First trimester femur-length/biparietal diameter (FL/BPD), FL/abdominal circumference (AC) and FL/foot for the screening of skeletal dysplasia were evalauted. METHOD: Case-control study: pregnancies with molecular confirmation of skeletal dysplasia undergoing nuchal translucency (January_2007-December_2021). Controls included pregnancies without fetal abnormalities. Performance of FL/BPD, FL/AC and FL/foot was evaluated by receiver operating characteristic curves. RESULTS: Twenty-eight skeletal dysplasia cases were identified; 17 (60.71%) corresponded to lethal types. Compared to 184 controls, cases had a lower median FL/BPD (0.34 [IQR 0.30-0.38] vs. 0.44 [IQR 0.39-0.48]; p < 0.001), FL/AC (0.13 [IQR 0.09-0.15] vs. 0.15 [IQR 0.13-0.16]; p = 0.001) and FL/foot (0.84 [IQR 0.76-0.91] vs. 1.01 [IQR 0.94-1.11]; p < 0.001). FL/BPD and FL/foot ratios had a superior area under the curve (0.846 and 0.853, respectively) than FL/AC (0.64). The probability of diagnosing skeletal dysplasia increased at least 9-fold if FL/BPD <0.376 (OR 26.05, 95% CI 9.79-69.3; p < 0.001) and 14-fold if FL/foot <0.891 (OR 39.46, 95% CI 14.17-109.9; p < 0.001). Low FL/BPD and FL/foot were associated significantly with lethal types compared to viable skeletal dysplasia. CONCLUSIONS: First trimester FL/BPD and FL/foot may be of clinical utility in the detection of skeletal dysplasia especially when there is another suspicious sonographic sign or when there is a relevant family history before overt second trimester sonographic markers become apparent.

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

OBJECTIVES: The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. DESIGN: This was an observational retrospective study. SETTINGS: A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. PARTICIPANTS: A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. RESULTS: More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p<0.001), degenerative spine (OR=0.296, p=0.027) and expedited indications (OR=6.095, p<0.001) were independent factors for being operated on during the pandemic. CONCLUSIONS: Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures.

Pharmacological treatment in pregnant women with moderate symptoms of coronavirus disease 2019 (COVID-19) pneumonia.

OBJECTIVE: Pregnant women with moderate symptoms of COVID-19 are at risk for progressing to severe or critical illness. While there are limited data on the management of severe COVID-19 during pregnancy, information on pharmacological treatments of moderate COVID-19 is lacking. We report clinical outcomes of pregnant women hospitalized due to moderate COVID-19 illness treated with a 5-day course of remdesivir, antibiotics, and/or glucocorticoids. MATERIALS AND METHODS: Case series of pregnant women hospitalized with moderate symptoms of COVID -19 pneumonia at two INOVA Health System hospitals from April 1 to December 31, 2020. Primary outcome was clinical recovery (breathing on ambient air and/or hospital discharge) on hospital day 7 (HD7). Cox regression analysis was performed to evaluate which variables were associated with the primary outcome. RESULTS: Out of 748 pregnant women with confirmed infection by reverse transcriptase polymerase chain reaction, 35 were hospitalized due to moderate symptoms of COVID-19 pneumonia (median gestational age 29 weeks). There was no maternal death. Seventeen patients received remdesivir within 48 hours of hospitalization: 15 remained with moderate symptoms and 2 (who also received glucocorticoids) had progressed to critical COVID-19 at remdesivir initiation; all 17 women in this group achieved clinical recovery on HD7. Seven women received remdesivir >48 hours following admission after they began treatment with glucocorticoids ± antibiotics and worsened to severe or critical disease; they all required supplemental oxygen on HD7. Eleven women were treated with antibiotics ± glucocorticoids but no remdesivir; on HD7, 3/11 achieved clinical recovery. Clinical recovery was significantly different among treatment groups; p < 0.001. When analyzing only women who remained with moderate symptoms at pharmacological treatments initiation, all 15 on remdesivir and only 3 of 11 on antibiotics achieved clinical recovery on HD7; p < 0.001. Delaying remdesivir for >48 hours after admission (HR 2.32, 95% CI 1.45-4.16) and >4-day duration of symptoms prior to hospitalization (HR 1.65, 95% CI 1.27-3.50) had an inverse association with clinical recovery. Incidental oligohydramnios was seen in 3/24 (12.5%) of women within 5 days of completing remdesivir treatment. Elevated transaminases was prevalent in women treated with remdesivir (8/24, 33.3%). CONCLUSION: In our cohort, prompt initiation of remdesivir in pregnant women hospitalized with moderate symptoms of COVID-19 pneumonia within 48 hours of admission prevented worsening and allowed a fast clinical recovery by HD7. Deferring remdesivir for >48 hours after hospitalization and duration of symptoms >4 days before admission were independently associated with delayed clinical recovery and longer hospital admission. Ultrasound evaluation of the amniotic fluid in patients recovering from COVID-19 hospitalization should be considered.

Relevance of pneumoperitoneum in the conservative approach to complicated acute diverticulitis. A retrospective study identifying risk factors associated with treatment failure.

BACKGROUND: The aim of this study is to evaluate the relevance of pneumoperitoneum on the success rate of non-operative management (NOM) of patients with complicated acute diverticulitis (AD), and the risk factors associated with failure. METHODS: Observational retrospective cohort study of patients attended at the emergency department for AD from January 2015-August 2019. Patient demographics, blood tests, radiological data and initial treatment strategies were registered. NOM, based on intravenous antibiotics (ATB) and bowel rest, was defined as unsuccessful when emergency surgery (ES) and/or infection-related death took place. Patients initially treated with ES were excluded. Analysis was done with the IBM SPSS statistics 23.0.0.2 software. RESULTS: According to modified Hinchey and WSES criteria, 99 (12%) of 826 AD episodes were complicated, with pneumoperitoneum on the CT scan in 89 (90.5%). NOM was undertaken in 93 (94%) cases, with a 91.5% success rate. Multivariate analysis revealed ASA class III-IV, and the presence of fluid collections >3 cm in diameter, but not distant free air, to be associated with NOM failure. However, the success rate of NOM was significantly higher in patients with pericolic pneumoperitoneum (98.5%) than in those with distant free air (80%) (P=0.02). Risk factors of NOM failure were an advanced age, high CRP and WBC values, and the presence of free fluid in >2 abdominal quadrants. CONCLUSIONS: NOM in hemodynamically stable patients with complicated AD is a safe and feasible approach, even in the context of distant free air. Nevertheless, patients with isolated pericolic air did better in our series.

Plasminogen Activator Inhibitor-1 and Adiponectin Are Associated With Metabolic Syndrome Components.

BACKGROUND: We aimed to study the associations of adipocytokines, endothelial damage markers, and high-sensitivity C-reactive protein (hs-CRP) with metabolic syndrome (MetS) components. METHODS: This cross-sectional study included 202 subjects categorized into MetS and No-MetS according to Harmonizing Adult Treatment Panel III. RESULTS: Subjects with MetS showed higher levels of proinflammatory molecules but significantly lower adiponectin levels than subjects with No-MetS. Among the studied adipocytokines, plasminogen activator inhibitor-1 (PAI-1) and adiponectin showed the strongest associations with most MetS components. PAI-1 was associated with MetS (odds ratio (OR) 1.107 (1.065-1.151), P < 0.0001), whereas adiponectin was inversely associated with MetS (OR 0.710 (0.610-0.825), P < 0.0001). Following adjustment by sex, age, body mass index, and 24-hour urinary sodium excretion in a multivariate analysis, the association of PAI-1 (OR 1.090 (1.044-1.137), P < 0.0001) and adiponectin (OR 0.634 (0.519-0.775), P < 0.0001) with MetS remained significant. Multivariate analyses supported a model in which systolic blood pressure (BP) could be predicted by PAI-1, hs-CRP, and matrix metalloproteinase 2 (R2 = 0.125; P = 0.04); diastolic BP (R2 = 0.218; P = 0.0001) and glucose (R2 = 0.074; P = 0.0001) could be predicted by PAI-1; waist circumference could be predicted by PAI-1 and hs-CRP (R2 = 0.28; P = 0.016). Receiver operating characteristic curve analysis showed that a PAI-1 concentration had the best sensitivity and specificity for discriminating subjects with MetS. CONCLUSION: PAI-1 and adiponectin rendered the most robust associations with MetS components in a general population, indicating that unfavorable adipose tissue performance is a key contributor to these metabolic anomalies. Further prospective analyses should allow establishing whether these adipocytokines can anticipate the progress of MetS and cardiovascular risk.

Colorectal Cancer in Elderly Patients with Surgical Indication: State of the Art, Current Management, Role of Frailty and Benefits of a Geriatric Liaison.

Six out of every 10 new colorectal cancer (CRC) diagnoses are in people over 65 years of age. Current standardized surgical approaches have proved to be tolerable on the elderly population, although post-operative complications are more frequent than in the younger CRC population. Frailty is common in elderly CRC patients with surgical indication, and it appears to be also associated with an increase of post-operative complications. Fast-track pathways have been developed to assure and adequate post-operative recovery, but comprehensive geriatric assessments (CGA) are still rare among the preoperative evaluation of elderly CRC patients. This review provides a thorough study of the effects that a CGA assessment and a geriatric intervention have in the prognosis of CRC elderly patients with surgical indication.

Comparison of two combined antiretroviral treatment regimens in the management of HIV in pregnancy: an observational study.

OBJECTIVE: Combined antiretroviral therapy (cART) in pregnancy traditionally included two nucleoside reverse transcriptase inhibitors plus 1 protease inhibitor (PI). Recently, integrase strand transfer inhibitors (INSTI) have been approved for use in pregnancy. We sought to compare the rate of undetectable VL near delivery in pregnant HIV-infected women receiving INSTI-based versus PI-based cART. MATERIAL AND METHODS: Prospective cohort study (January 2010-March 2017) of pregnant HIV-infected pregnancies receiving care in a single obstetric infectious disease clinic. Included pregnancies (total = 171; INSTI - group = 111, PI - group = 60) had at least 2 VL (before and after intervention) during pregnancy. The primary outcome was the rate of undetectable VL near delivery. RESULTS: We found comparable rates of undetectable HIV VL near delivery in pregnancies treated with INSTI-cART (74/111, 66.7%) compared to PI-cART (34/60, 56.7%; [adjusted p = .116, RR 1.26, 95% CI 0.92-2.59]). Compared to the PI-group, pregnancies in the INSTI-group showed lower median HIV VL near delivery (20 versus 50 copies/mL; adjusted p = .0454) and greater VL reduction (adjusted p = .0185). There were 3/171 (1.75%) infants diagnosed with HIV, 1 in the INSTI-group and 2 in the PI-group (p = .5635, RR 0.51, 95% CI 0.10-2.53). CONCLUSION: Pregnant HIV-infected women receiving either INSTI- or PI-based cART achieved comparable rates of undetectable HIV VL near delivery with similar perinatal transmission.

Differences in maternal gene expression in Cesarean section delivery compared with vaginal delivery.

Cesarean section (CS) is recognized as being a shared environmental risk factor associated with chronic immune disease. A study of maternal gene expression changes between different delivery modes can add to our understanding of how CS contributes to disease patterns later in life. We evaluated the association of delivery mode with postpartum gene expression using a cross-sectional study of 324 mothers who delivered full-term (≥ 37 weeks) singletons. Of these, 181 mothers had a vaginal delivery and 143 had a CS delivery (60 with and 83 without labor). Antimicrobial peptides (AMP) were upregulated in vaginal delivery compared to CS with or without labor. Peptidase inhibitor 3 (PI3), a gene in the antimicrobial peptide pathway and known to be involved in antimicrobial and anti-inflammatory activities, showed a twofold increase in vaginal delivery compared to CS with or without labor (adjusted p-value 1.57 × 10-11 and 3.70 × 10-13, respectively). This study evaluates differences in gene expression by delivery mode and provides evidence of antimicrobial peptide upregulation in vaginal delivery compared to CS with or without labor. Further exploration is needed to determine if AMP upregulation provides protection against CS-associated diseases later in life.

Molecular Pathways Leading to Induction of Cell Death and Anti-Proliferative Properties by Tacrolimus and mTOR Inhibitors in Liver Cancer Cells.

BACKGROUND/AIMS: Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with portal hypertension and/or increased bilirubinemia, but without vascular-associated diseases. Tumor recurrence, which is the main drawback for the survival of patients submitted to OLT for HCC, has been related to tumor-related variables and the immunosuppressive therapies. We have previously shown that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in liver cancer cells. This study identified the role of the immunosuppressant partners such as FK506-binding proteins (FKBPs) in the induction of cell death and arrest of cell proliferation by immunosuppressants in two representative liver cancer cells. METHODS: The regulation of endoplasmic reticulum (ER) stress, apoptosis/autophagy, cell proliferation, and FKBPs expression was determined in Tacrolimus-, Sirolimus- and Everolimus-treated primary human hepatocytes, and hepatoma HepG2 and Huh7 cell lines. The functional repercussion of FKBPs on cell death and proliferation was also addressed using the siRNA technology. The assessed antitumoral properties of the immunosuppressants were associated to microRNAs (miRNAs) pattern. RESULTS: The enhanced pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with increased protein kinase RNA-like endoplasmic reticulum kinase (PERK)-related ER stress, Ser15P-p53/p53 ratio and p21 protein expression that may counterbalance the risk of proliferative upregulation caused by enhanced Thr172P-Cdk4/Cdk4 activation in liver cancer cells. The inhibition of the mTOR pathway by Sirolimus and Everolimus was related to an induction of autophagy; and at a high dose, these drugs impaired translation likely at a very early step of the elongation phase. Tacrolimus and mTOR inhibitors increased the protein expression of FKBP12 and FKBP51 that appeared to play pro-survival role. Interestingly, the administration of immunosuppressants yields a specific pattern of miRNAs. Tacrolimus and mTOR inhibitors decreased miR-92a-1-5p, miR-197-3p, miR-483-3p and miR-720, and increased miR-22-3p, miR-376a-3p, miR-663b, miR-886-5p, miR-1300 and miR-1303 expressions in HepG2 cells. CONCLUSION: The more potent pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with an increased activation of PERK and p53 signaling, and p21 protein expression. FKBP12 and FKBP51 appeared to be the most relevant partners of Tacrolimus and mTOR inhibitors exerting a pro-survival effect in HepG2 cells. The observed effects of immunosuppressants were related to a specific miRNA signature in liver cancer cells.

Fetal acute cerebral vasoreactivity to maternal hyperoxia in low-risk pregnancies: a cross-sectional study.

OBJECTIVE: To establish whether fetal cerebral vasoreactivity (CVRO2 ), following maternal hyperoxia, is predicted by fetal cerebral and uteroplacental Doppler pulsatility indices (PI) at baseline, fetal pulmonary vasoreactivity to oxygen (PVRO2 ), gestational age (GA), or sex. METHODS: Pulsatility index of middle (MCA), anterior (ACA), posterior cerebral (PCA), umbilical (UA), uterine (UtA), and branch of the pulmonary arteries (PA) were obtained, by ultrasound, before (baseline), during (hyperoxia) and after 15 minutes of maternal administration of 8 L/min of 100% oxygen, through a non-rebreathing face mask, in normal singleton pregnancies within 20 to 38 weeks' gestation. CVRO2 was defined as changes greater than zero in z score of PI of the cerebral arteries from baseline to hyperoxia. Logistic modeling was applied to identify CVRO2 predictors. RESULTS: A total of 97 pregnancies were eligible. In the overall population, median z scores of PI of MCA, ACA, and PCA did not differ between study phases. Based on the logistic model, baseline z scores for cerebral PI and GA were the best predictors of CVRO2 . CONCLUSIONS: In low-risk pregnancies, fetal CVRO2 to hyperoxia does not occur uniformly but depends on cerebral PI and GA at baseline. These findings may provide useful reference points when oxygen is administered in high-risk pregnancies.

Trasplante hepático dominó con injerto procedente de donante en muerte circulatoria (Maastricht III) / Successful domino liver transplantation using a graft from a controlled donation after circulatory death (Maastricht III)

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Disability and quality of life in heart failure patients: a cross-sectional study.

BACKGROUND: Although both hospitalization and mortality due to heart failure (HF) have been widely studied, less is known about the impact of HF on disability and quality of life. AIM: To assess the degree of disability and quality of life in HF patients attended at family medicine centres. DESIGN AND SETTING: Cross-sectional study of a cohort of HF patients attended at family medicine centres. METHODS: Disability was assessed with the WHODAS 2 questionnaire, which provides a global and six domain scores that is understanding and communication, getting around, self-care, getting along with people, life activities and participation in society. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire, which furnishes a global and two domain scores, physical and emotional. RESULTS: A breakdown of the results showed that 28% of patients had moderate disability and 16.7% had severe disability, with the most important areas affected being: life activities, 8.9% extreme disability and 30.3% severe disability; getting around, 34.6% severe disability and 2% extreme disability; and participation in society, 53.3% moderate-severe disability. Quality of life was mildly affected. New York Heart Association (NYHA) Functional Classification and sex were the major determinants of disability and quality of life. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists were associated with better scores in the "getting around" and "life activity" domains. CONCLUSION: HF patients in primary care show an important degree of disability and an acceptable quality of life.