Exposure to obinutuzumab does not affect outcomes of SARS-CoV-2 infection in vaccinated patients with newly diagnosed advanced-stage follicular lymphoma.

URBAN is a multicentric, ambispective study evaluating the effectiveness and safety of obinutuzumab-based immuno-chemotherapy and maintenance in patients with untreated advanced follicular lymphoma (FL). The study began before the COVID-19 emergency declaration in Italy. It is currently ongoing for follow-up, and the enrolment timeline encompassed different stages of the pandemic, various vaccination roll-out phases and prevalence of SARS-CoV-2 variants. Outcomes of interest of the present sub-analysis included SARS-CoV-2 infection rates and COVID-19-related hospitalizations/deaths. At data cut-off, 86 (28.8%) and 213 patients (71.2%) were treated before and during/after the COVID-19 outbreak respectively; 294 (98.3%) completed the induction, 31 (10.4%) completed maintenance and 170 (56.9%) were still on maintenance. Overall, 245 patients (81.9%) received at least one SARS-CoV-2 vaccine dose: 13.5%, 31.4% and 55.1% received one, two and three doses respectively. We observed a substantial decrease in COVID-19-related mortality rates in pre- versus post-vaccination phases, along with a reduction in COVID-19-related outcomes due to the shift from alpha/delta to omicron variant predominance. No differences emerged between patients given maintenance or not, although the schedule was modified in 65% of cases. To our knowledge, URBAN represents the largest dataset of COVID-19-related outcomes in FL patients extensively exposed to obinutuzumab. ClinicalTrials.gov identifier: NCT04034056.

Performance of helmet CPAP using different configurations: Turbine-driven ventilators vs Venturi devices.

BACKGROUND: Traditionally, Venturi-based flow generators have been preferred over mechanical ventilators to provide continuous positive airway pressure (CPAP) through the helmet (h-CPAP). Recently, modern turbine-driven ventilators (TDVs) showed to be safe and effective in delivering h-CPAP. We aimed to compare the pressure stability during h-CPAP delivered by Venturi devices and TDVs and assess the impact of High Efficiency Particulate Air (HEPA) filters on their performance. METHODS: We performed a bench study using an artificial lung simulator set in a restrictive respiratory condition, simulating two different levels of patient effort (high and low) with and without the interposition of the HEPA filter. We calculated the average of minimal (Pmin), maximal (Pmax) and mean (Pmean) airway pressure and the time product measured on the airway pressure curve (PTPinsp). We defined the pressure swing (Pswing) as Pmax - Pmin and pressure drop (Pdrop) as End Expiratory Pressure - Pmin. RESULTS: Pswing across CPAP levels varied widely among all the tested devices. During "low effort", no difference in Pswing and Pdrop was found between Venturi devices and TDVs; during high effort, Pswing (p<0.001) and Pdrop (p<0.001) were significantly higher in TDVs compared to Venturi devices, but the PTPinsp was lower (1.50 SD 0.54 vs 1.67 SD 0.55, p<0.001). HEPA filter addition almost doubled Pswing and PTPinsp (p<0.001) but left unaltered the differences among Venturi and TDVs systems in favor of the latter (p<0.001). CONCLUSIONS: TDVs performed better than Venturi systems in delivering a stable positive pressure level during h-CPAP in a bench setting.

Femoral Access-Site Complications with Tenecteplase versus Alteplase before Mechanical Thrombectomy for Large-Vessel-Occlusion Stroke.

BACKGROUND AND PURPOSE: IV thrombolysis with alteplase before mechanical thrombectomy for emergent large-vessel-occlusion stroke is associated with access-site bleeding complications. However, the incidence of femoral access-site complications with tenecteplase before mechanical thrombectomy requires exploration. Here, femoral access-site complications with tenecteplase versus alteplase before mechanical thrombectomy for large-vessel-occlusion stroke were compared. MATERIALS AND METHODS: All patients receiving IV thrombolytics before mechanical thrombectomy for large-vessel-occlusion stroke who presented from January 2020 to August 2022 were reviewed. In May 2021, our health care system switched from alteplase to tenecteplase as the primary thrombolytic for all patients with stroke, facilitating the comparison of alteplase-versus-tenecteplase femoral access-site complication rates. Major (requiring surgery) and minor (managed conservatively) access-site complications were assessed. RESULTS: One hundred thirty-nine patients underwent transfemoral mechanical thrombectomy for large-vessel-occlusion stroke, of whom 46/139 (33.1%) received tenecteplase and 93/139 (66.9%) received alteplase. In all cases (n = 139), an 8F sheath was inserted without sonographic guidance, and vascular closure was obtained with an Angio-Seal. Baseline demographics, concomitant antithrombotic medications, and periprocedural coagulation lab findings were similar between groups. The incidence of conservatively managed groin hematomas (2.2% versus 4.3%), delayed access-site oozing requiring manual compression (6.5% versus 2.2%), and arterial occlusion requiring surgery (2.2% versus 1.1%) was similar between the tenecteplase and alteplase groups, respectively (P = not significant). No dissection, arteriovenous fistula, or retroperitoneal hematoma was observed. CONCLUSIONS: Tenecteplase compared with alteplase before mechanical thrombectomy for large-vessel-occlusion stroke is not associated with an alteration in femoral access-site complication rates.

Nitrogen dioxide pollution increases vulnerability to COVID-19 through altered immune function.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

Outcomes of Mechanical Thrombectomy in the Early (<6-hour) and Extended (≥6-hour) Time Window Based Solely on Noncontrast CT and CT Angiography: A Propensity Score-Matched Cohort Study.

BACKGROUND AND PURPOSE: Current stroke care recommendations for patient selection for mechanical thrombectomy in the extended time window demand advanced imaging to determine the stroke core volume and hypoperfusion mismatch, which may not be available at every center. We aimed to determine outcomes in patients selected for mechanical thrombectomy solely on the basis of noncontrast CT and CTA in the early (<6-hour) and extended (≥6-hour) time windows. MATERIALS AND METHODS: Consecutive mechanical thrombectomies performed for acute large-vessel occlusion ischemic (ICA, M1, M2) stroke between February 2016 and August 2020 were retrospectively reviewed. Eligibility was based solely on demographics and noncontrast CT (ASPECTS) and CTA, due to the limited availability of perfusion imaging during the study period. Propensity score matching was performed to compare outcomes between time windows. RESULTS: Of 417 mechanical thrombectomies performed, 337 met the inclusion criteria, resulting in 205 (60.8%) and 132 (39.2%) patients in the 0- to 6- and 6- to 24-hour time windows, respectively. The ASPECTS was higher in the early time window (9; interquartile range = 8-10) than the extended time window (9; interquartile range = 7-10; P = .005). Propensity score matching yielded 112 well-matched pairs. Equal rates of TICI 2b/3 revascularization and symptomatic intracranial hemorrhage were observed. A favorable functional outcome (mRS 0-2) at 90 days was numerically more frequent in the early window (45.5% versus 33.9%, P = .091). Mortality was numerically more frequent in the early window (25.9% versus 17.0%, P = .096). CONCLUSIONS: Patients selected for mechanical thrombectomy in the extended time window solely on the basis of noncontrast CT and CTA still achieved decent rates of favorable 90-day functional outcomes, not statistically different from patients in the early time window.

Sportomics: metabolomics applied to sports. The new revolution?

Sportomics is the application of metabolomics in sports to investigate the metabolic effects of physical exercise on individuals, whether they are professional athletes or not. Metabolomics is one of the "omics" sciences that provide a picture of the metabolic state of a person in physiological or pathological conditions. This is achieved through the analysis of metabolites present in a biological fluid, such as saliva, blood, feces, and urine. The authors revised the recent literature concerning this topic and discussed the useful information that sportomics can provide and the limits of the current experimental settings. Furthermore, in the future, sportomics analyses could be used to prevent and manage injuries as it would be known in advance if an athlete is more prone to experience muscular damage or fatigue. Following more trials, it would also be possible to set the best diet and training programs to get the best performances out of the athletes. Moreover, based on their metabolic profiles, both adults and children could choose tailored physical training in order to preserve and improve their health.

Vitamin D and disease severity in bronchiectasis.

BACKGROUND: Bronchiectasis is a complex respiratory disease characterised by permanent dilatation of bronchi. Vitamin D plays a role in infective disease by modulating the inflammation. Patients affected by bronchiectasis are frequently Vitamin D deficient and it correlates with lung function decline. We want to understand if there is a correlation between Vitamin D and clinical and radiological severity of bronchiectasis. METHODS: We included 57 patients (17 males/40 female with mean age 60 ±â€¯12 years) between October 2017 and March 2018. We excluded patients with cystic fibrosis, traction bronchiectasis and reporting Vitamin D supplementation. Bronchiectasis severity index (BSI) and Bhalla score were calculated, blood inflammatory markers and Vit. D were measured and lung function tests were performed. RESULTS: Vitamin D is deficient in 64% of patients, sufficient in 36% and normal in 7%. Mean BSI is 7.5 ±â€¯5 and mean Bhalla score is 16 ±â€¯4. Vitamin D levels correlate with Bhalla score (R2 = 0.68, p < 0.001) and BSI (R2 = 0.58, p < 0.0001). The correlation appears to be stronger than other markers of inflammation such as ESR and CRP [R2 = 0.33, p = 0.001 and R2 = 0.39, p = 0.001 respectively]. CONCLUSIONS: We consider Vitamin D as a good predictor of clinical and radiological severity of bronchiectasis.

Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ.

This corrects the article DOI: 10.1038/onc.2017.75.

Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ.

Recent evidences suggest that stearoyl-CoA-desaturase 1 (SCD1), the enzyme involved in monounsaturated fatty acids synthesis, has a role in several cancers. We previously demonstrated that SCD1 is important in lung cancer stem cells survival and propagation. In this article, we first show, using primary cell cultures from human lung adenocarcinoma, that the effectors of the Hippo pathway, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), are required for the generation of lung cancer three-dimensional cultures and that SCD1 knock down and pharmacological inhibition both decrease expression, nuclear localization and transcriptional activity of YAP and TAZ. Regulation of YAP/TAZ by SCD1 is at least in part dependent upon ß-catenin pathway activity, as YAP/TAZ downregulation induced by SCD1 blockade can be rescued by the addition of exogenous wnt3a ligand. In addition, SCD1 activation of nuclear YAP/TAZ requires inactivation of the ß-catenin destruction complex. In line with the in vitro findings, immunohistochemistry analysis of lung adenocarcinoma samples showed that expression levels of SCD1 co-vary with those of ß-catenin and YAP/TAZ. Mining available gene expression data sets allowed to observe that high co-expression levels of SCD1, ß-catenin, YAP/TAZ and downstream targets have a strong negative prognostic value in lung adenocarcinoma. Finally, bioinformatics analyses directed to identify which gene combinations had synergistic effects on clinical outcome in lung cancer showed that poor survival is associated with high co-expression of SCD1, ß-catenin and the YAP/TAZ downstream target birc5. In summary, our data demonstrate for the first time the involvement of SCD1 in the regulation of the Hippo pathway in lung cancer, and point to fatty acids metabolism as a key regulator of lung cancer stem cells.

Emerging biomarkers and metabolomics for assessing toxic nephropathy and acute kidney injury (AKI) in neonatology.

Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called "omics" allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS), proton nuclear magnetic resonance (1H NMR), and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods.

Metabolomics network characterization of resuscitation after normocapnic hypoxia in a newborn piglet model supports the hypothesis that room air is better.

Perinatal asphyxia is attributed to hypoxia and/or ischemia around the time of birth and may lead to multiorgan dysfunction. Aim of this research article is to investigate whether different metabolomic profiles occurred according to oxygen concentration administered at resuscitation. In order to perform the experiment, forty newborn piglets were subjected to normocapnic hypoxia and reoxygenation and were randomly allocated in 4 groups resuscitated with different oxygen concentrations, 18%, 21%, 40%, and 100%, respectively. Urine metabolic profiles at baseline and at hypoxia were analysed by (1)H-NMR spectroscopy and metabolites were also identified by multivariate statistical analysis. Metabolic pathways associations were also built up by ingenuity pathway analysis (IPA). Bioinformatics analysis of metabolites characterized the effect of metabolism in the 4 groups; it showed that the 21% of oxygen is the most "physiological" and appropriate concentration to be used for resuscitation. Our data indicate that resuscitation with 21% of oxygen seems to be optimal in terms of survival, rapidity of resuscitation, and metabolic profile in the present animal model. These findings need to be confirmed with metabolomics in human and, if so, the knowledge of the perinatal asphyxia condition may significantly improve.

Clinical metabolomics and hematic ADMA predict the future onset of cardiorenal syndrome in young grown-up subjects who were born preterm.

OBJECTIVES: To look for differences in the urinary metabolic profile and in the hematic asymmetric dimethylarginine (ADMA) levels between a group of young adults born preterm with an extremely low birthweight (<1000 g; ex-ELBW; n=19) and a control group of subjects born at term with a weight appropriate for their gestational age (AGA; n=13); and to look for a possible correlation between the urinary metabolic profile in ex-ELBW and their hematic levels of ADMA. DESIGN AND METHODS: Urine samples were analyzed by (1)H nuclear magnetic resonance spectroscopy, and then submitted to unsupervised and supervised multivariate analysis. Samples of blood were collected and ADMA concentration was assessed by high-performance liquid chromatography. RESULTS: Using supervised PLS-DA (partial least squares discriminant analysis) model, the authors were able to discriminate between ex-ELBW and AGA. Statistically significant differences were detected in the ADMA levels between ex-ELBW and AGA (p<0.02). Ex-ELBW metabolic profile correlated with ADMA concentrations (r=0.456, p<0.05). Conversely, ADMA levels in AGA did not correlated with their metabolic profiles. CONCLUSIONS: This study demonstrates the relevance of the metabolomic technique as a predictive tool of the metabolic status in ex-ELBW. The relationship between ex-ELBW urinary metabolic profile and their blood ADMA levels suggests the presence of a subclinical cardio-renal involvement in these subjects.

Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells.

In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These results suggest that SCD1 is a critical target in lung cancer tumor-initiating cells.

Colostrum in menopause effects on vaginal cytology/symptoms.

The aim of this study was to assess the effects of three weeks of daily colostrum cream on vaginal cytology and local symptoms related to menopause. Genito-urinary symptoms and cell morphology were analyzed at time 0 (T0) and after three weeks (16 +/- days since the end of treatment) at time 1 (T1). Dyspareunia, vaginal dryness, and maturation index (MI) reached a statistically significant difference between T0 and T1. The results proved to be an alternative treatment for vaginal distress caused by lack of hormones in patients in which hormonal treatment is contraindicated.

NGAL and metabolomics: the single biomarker to reveal the metabolome alterations in kidney injury.

Conditions affecting kidney structure and function can be considered acute or chronic, depending on their duration. Acute kidney injury (AKI) is one of a number of acute kidney diseases and consists of an abrupt decline in kidney function after an injury leading to functional and structural changes. The widespread availability of enabling technologies has accelerated the rate of novel biomarker discovery for kidney injury. The introduction of novel biomarkers in clinical practice will lead to better preventative and therapeutic interventions and to improve outcomes of critically ill patients. A number of biomarkers of functional change and cellular damage are under evaluation for early diagnosis, risk assessment, and prognosis of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as the most promising biomarker of kidney injury; this protein can be measured by commercially available methods in whole blood, plasma, serum, and urine. Concomitantly, metabolomics appears to be a snapshot of the chemical fingerprints identifying specific cellular processes. In this paper, we describe the role of NGAL for managing AKI and the potential benefits deriving from the combined clinical use of urine NGAL and metabolomics in kidney disease.

Intensive care of patients requiring open abdomen treatment: a case-series analysis.

BACKGROUND: This retrospective overview examines the management of patients with temporary open abdomen (OA). METHODS: The clinical characteristics and intensive care treatment of 34 consecutive patients with OA (1996-2012) were reviewed. RESULTS: Average age was 61 years, SAPS II score 43, SOFA 8. Two patients had non-contaminated abdomen; 12 had intact gut (only 8 later during stay); 7 repaired gut (only later 4); 13 cutaneous stoma (later 14), and 2 entero-atmospheric fistula (later 8+1 entero-enteral). The median ICU stay was 48 [36-94] days. One quarter of the 2376 ICU-days were classified as severe sepsis/septic shock (antibiotics were given for two thirds of the stay); three quarters were with ventilation; in 95% of days sedatives were given (mainly enterally). Continuous cavity lavage was done in three quarters of days; in 3% of days patients were fasted whereas >20 kcal/kg was given for 74% of days; we fed the gut in 95% of fed-days, in half of them combined with parenteral nutrition. Complications are discussed; mortality was 32.4%, limited to the ICU stay. CONCLUSION: The intensive care of patients with OA is challenging but can achieve better outcomes than expected. Continuous abdominal lavage improves the evacuation of contaminated fluid or debris and, coupled with antiseptics and low antibiotic pressure, reinforces the control of infection. The gut can be used for nutrition (even without gastrointestinal continuity), and long-term light sedation (mainly enteral) with minimal impact on perfusion, ventilation and gut motility.

The importance of biomarkers in neonatology.

Despite a 35% decline in the mortality rate for infants aged <5 years over the past two decades, every year nearly 40% of all deaths in this age group occur in the neonatal period, defined as the first 28 days of life. New knowledge on molecular and biochemical pathways in neonatal diseases will lead to the discovery of new candidate biomarkers potentially useful in clinical practice. In the era of personalized medicine, biomarkers may play a strategic role in accelerating the decline in neonatal mortality by assessing the risk of developing neonatal diseases, by implementing tailored therapeutic treatment, and by predicting the clinical outcome. However, there is an urgent need to reduce the gap in translating newly acquired knowledge from bench to bedside. Traditional and candidate biomarkers for neonatal sepsis and necrotizing enterocolitis will be discussed in this review, such as C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA), soluble form of CD14 subtype presepsin (sCD14-ST), lipolysaccharide binding protein (LBP), angiopoietins (Ang)-1 and -2, soluble form of triggering receptor expressed on myeloid cells (sTREM-1), soluble form of urokinase-type plasminogen activator receptor (suPAR), platelet-activating factor (PAF) and calprotectin. New frontiers in managing critically ill newborns may be opened by metabolomics, a diagnostic tool based on the recognition of metabolites contained in biological fluids. Metabolomics represents the passage from a descriptive science to a predictive science, having the potential to translate benchtop research to real clinical benefits.

Metabolomics in neonatology: fact or fiction?

The newest 'omics' science is metabolomics, the latest offspring of genomics, considered the most innovative of the 'omics' sciences. Metabolomics, also called the 'new clinical biochemistry', is an approach based on the systematic study of the complete set of metabolites in a biological sample. The metabolome is considered the most predictive phenotype and is capable of considering epigenetic differences. It is so close to the phenotype that it can be considered the phenotype itself. In the last three years about 5000 papers have been listed in PubMed on this topic, but few data are available in the newborn. The aim of this review, after a description of background and technical procedures, is to analyse the clinical applications of metabolomics in neonatology, covering the following points: gestational age, postnatal age, type of delivery, zygosity, perinatal asphyxia, intrauterine growth restriction, prenatal inflammation and brain injury, respiratory, cardiovascular renal, metabolic diseases; sepsis, necrotizing enterocolitis and antibiotic treatment; nutritional studies on maternal milk and formula, pharma-metabolomics, long-term diseases. Pros and cons of metabolomics are also discussed. All this comes about with the non-invasive collection of a few drops of urine (exceptionally important for the neonate, especially those of low birth weight). Only time and large-scale studies to validate initial results will place metabolomics within neonatology. In any case, it is important for perinatologists to learn and understand this new technology to offer their patients the utmost in diagnostic and therapeutic opportunities.

The sensibility and specificity of cerebral oximetry, measured by INVOS - 4100, in patients undergoing carotid endarterectomy compared with awake testing.

BACKGROUND: Selective shunting during carotid endarterectomy (CEA) is advocated to reduce shunt-related stroke. Cerebral monitoring is essential for temporary carotid shunting. Many techniques are available for cerebral monitoring; however, none is superior to monitoring the patient's neurological status (awake testing) while performing the procedure under local anesthesia (LA). Cerebral oximetry (CO) has previously been used to show the adequacy of cerebral circulation in patients undergoing CEA. This investigation was designed to compare the performance of the INVOS-4100 cerebral oximeter and the neurologic functions, by means of detecting cerebral ischemia induced by carotid cross-clamping, in patients undergoing CEA under LA, namely cervical plexus block. METHODS: Patients scheduled for CEA under LA were included. Patients converted to general anesthesia (GA) or other types of operations other than CEA were excluded from this study. We enrolled 100 consecutive patients from January 2009 to December 2010. Bilateral regional cerebrovascular oxygen saturation (rSO(2)) was monitored in all patients, in addition to the awake testing. Changes in rSO(2) following carotid artery clamping were recorded. A drop greater than 20% was considered as an indicator of cerebral ischemia that might predict the need for carotid shunting. Patients were only shunted based on the awake testing. RESULTS: Of the 100 patients undergoing CEA under LA, 9 showed a significant drop in rSO(2) (range: 22.6-32.8%, mean: 26.4%): only three of them required shunting, while the remaining 6 had no changes in consciousness after internal carotid artery (ICA) cross-clamping and it was not necessary to place a shunt (false positive). Compared to the preclamping values, a significant decrease in rSO(2) was found on the hemisphere of the operated side, while no significant change was observed contralaterally. Ninety-one patients had no significant changes of CO values: in 89 of them there was no consciousness deterioration, so we didn't place a shunt (true negative), but 2 patients showing a non-significant post-clamping decline in CO saturation (1.5% and 18.2%) required shunting based on the awake testing (2 false negative). In the current study, the median drop in rSO(2) was 19% (range: 1.5-26.4%) in the 5 patients that required shunting. This represents a sensitivity of 60% and a specificity of 25% for CO in comparison to the awake testing. CONCLUSION: The results of this study suggest that the usefulness of CO in predicting cerebral ischemia is modest. Cerebral monitoring with INVOS-4100 has a high negative predictive value, but the positive predictive value is low.

Review metabolomics: a new approach to drug delivery in perinatology.

The purpose of this review is to describe the state of the art of the pharmacological applications in perinatal medicine and highlight how a new emerging discipline, metabolomics, may have a significant impact on understanding complex biological processes associated with the drugs actions. Currently, there is great demand for new information regarding the use of drugs, especially during the perinatal period in order to minimize the occurrence of adverse drug reactions and to maximize the desired therapeutic effect. Metabolomics is a functional genomic tool concerned with the high-throughput identification, quantification and characterization of small molecule metabolites. This new technique has been shown to have a great impact on classifying phenotypes, investigation of physiological status, diagnosing disease, measuring the response to treatment, discovering biomarkers, and identifying perturbed pathways due to disease or treatment. Metabolic profiles appear to be a key factor in predicting the outcome of a pathological condition and the individual's response to a pharmacological treatment. This new systems biology tool may have important potential implication for pharmacological science, in particular drug discovery, development, and prediction of the drug's effects on the body by explaining the mechanisms by which drug response causes adverse effects.