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Objective Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. Design and methods In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. Results 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. Conclusions These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.

Postoperative delirium is a frequent occurrence in the elderly surgical population. As a comprehensive list of predictive factors remains unknown, an opioid-sparing approach incorporating regional anesthesia techniques has been suggested to decrease its incidence. Due to the lack of conclusive evidence on the topic, we conducted a systematic review and meta-analysis to investigate the potential impact of regional anesthesia and analgesia on postoperative delirium.PubMed, Embase, and the Cochrane central register of Controlled trials (CENTRAL) databases were searched for randomized trials comparing regional anesthesia or analgesia to systemic treatments in patients having any type of surgery. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We pooled the results separately for each of these two applications by random effects modelling. Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the certainty of evidence and strength of conclusions.Eighteen trials (3361 subjects) were included. Using regional techniques for surgical anesthesia failed to reduce the risk of postoperative delirium, with a relative risk (RR) of 1.21 (95% CI: 0.79 to 1.85); P=0.3800. In contrast, regional analgesia reduced the relative risk of perioperative delirium by a RR of 0.53 (95% CI: 0.42 to 0.68; P0.0001), when compared to systemic analgesia. Post-hoc subgroup analysis for hip fracture surgery yielded similar findings.These results show that postoperative delirium may be decreased when regional techniques are used in the postoperative period as an analgesic strategy. Intraoperative regional anesthesia alone may not decrease postoperative delirium since there are other factors that may influence this outcome.

The worlds of chronic pain and addiction continue to intersect too often in many ways. Chronic pain significantly impairs and disrupts the quality of life of millions of people worldwide. Opioids remain the most prescribed pharmacotherapy offered to patients to alleviate chronic pain. The extensive and often unnecessary prescription of opioids has created a surge in the prevalence of opioid use disorders and opioid overdose-related deaths. In this brief review, we aim to provide a bench-to-bedside overview of promising biomarkers, therapeutic targets, and challenges related to treating patients with chronic pain. We hope this review will inspire new opportunities and insights into the development of novel, nonaddictive treatments for chronic pain that will be available to patients in the near future.

Background: Intracranial pressure (ICP) normally ranges from 5 to 15 mmHg. Elevation in ICP is an important clinical indicator of neurological injury, and ICP is therefore monitored routinely in several neurological conditions to guide diagnosis and treatment decisions. Current measurement modalities for ICP monitoring are highly invasive, largely limiting the measurement to critically ill patients. An accurate noninvasive method to estimate ICP would dramatically expand the pool of patients that could benefit from this cranial vital sign. Methods: This article presents a spectral approach to model-based ICP estimation from arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) measurements. The model captures the relationship between the ABP, CBFV, and ICP waveforms and utilizes a second-order model of the cerebral vasculature to estimate ICP. Results: The estimation approach was validated on two separate clinical datasets, one recorded from thirteen pediatric patients with a total duration of around seven hours, and the other recorded from five adult patients, one hour and 48 minutes in total duration. The algorithm was shown to have an accuracy (mean error) of 0.4 mmHg and −1.5 mmHg, and a precision (standard deviation of the error) of 5.1 mmHg and 4.3 mmHg, in estimating mean ICP (range of 1.3 mmHg to 24.8 mmHg) on the pediatric and adult data, respectively. These results are comparable to previous results and within the clinically relevant range. Additionally, the accuracy and precision in estimating the pulse pressure of ICP on a beat-by-beat basis were found to be 1.3 mmHg and 2.9 mmHg respectively. Conclusion: These contributions take a step towards realizing the goal of implementing a real-time noninvasive ICP estimation modality in a clinical setting, to enable accurate clinical-decision making while overcoming the drawbacks of the invasive ICP modalities., National Institute of Neurological Disorders and Stroke (Grant R21-NS084264)

Understanding neuropathic pain presents several challenges, given the various mechanisms underlying its pathophysiological classification and the lack of suitable tools to assess its diagnosis. Furthermore, the response of this pathology to available drugs is still often unpredictable, leaving the treatment of neuropathic pain still questionable. In addition, the rise of personalized treatments further extends the ramified classification of neuropathic pain. While a few authors have focused on neuropathic pain clustering, by analyzing, for example, the presence of specific TRP channels, others have evaluated the presence of alterations in microRNAs to find tailored therapies. Thus, this review aims to synthesize the available evidence on the topic from a clinical perspective and provide a list of current demonstrations on the treatment of this disease.

OBJECTIVEIn the search for a reliable, cooperation-independent, noninvasive alternative to invasive intracranial pressure (ICP) monitoring in children, various approaches have been proposed, but at the present time none are capable of providing fully automated, real-time, calibration-free, continuous and accurate ICP estimates. The authors investigated the feasibility and validity of simultaneously monitored arterial blood pressure (ABP) and middle cerebral artery (MCA) cerebral blood flow velocity (CBFV) waveforms to derive noninvasive ICP (nICP) estimates.METHODSInvasive ICP and ABP recordings were collected from 12 pediatric and young adult patients (aged 2–25 years) undergoing such monitoring as part of routine clinical care. Additionally, simultaneous transcranial Doppler (TCD) ultrasonography–based MCA CBFV waveform measurements were performed at the bedside in dedicated data collection sessions. The ABP and MCA CBFV waveforms were analyzed in the context of a mathematical model, linking them to the cerebral vasculature’s biophysical properties and ICP. The authors developed and automated a waveform preprocessing, signal-quality evaluation, and waveform-synchronization “pipeline” in order to test and objectively validate the algorithm’s performance. To generate one nICP estimate, 60 beats of ABP and MCA CBFV waveform data were analyzed. Moving the 60-beat data window forward by one beat at a time (overlapping data windows) resulted in 39,480 ICP-to-nICP comparisons across a total of 44 data-collection sessions (studies). Moving the 60-beat data window forward by 60 beats at a time (nonoverlapping data windows) resulted in 722 paired ICP-to-nICP comparisons.RESULTSGreater than 80% of all nICP estimates fell within ± 7 mm Hg of the reference measurement. Overall performance in the nonoverlapping data window approach gave a mean error (bias) of 1.0 mm Hg, standard deviation of the error (precision) of 5.1 mm Hg, and root-mean-square error of 5.2 mm Hg. The associated mean and median absolute errors were 4.2 mm Hg and 3.3 mm Hg, respectively. These results were contingent on ensuring adequate ABP and CBFV signal quality and required accurate hydrostatic pressure correction of the measured ABP waveform in relation to the elevation of the external auditory meatus. Notably, the procedure had no failed attempts at data collection, and all patients had adequate TCD data from at least one hemisphere. Last, an analysis of using study-by-study averaged nICP estimates to detect a measured ICP > 15 mm Hg resulted in an area under the receiver operating characteristic curve of 0.83, with a sensitivity of 71% and specificity of 86% for a detection threshold of nICP = 15 mm Hg.CONCLUSIONSThis nICP estimation algorithm, based on ABP and bedside TCD CBFV waveform measurements, performs in a manner comparable to invasive ICP monitoring. These findings open the possibility for rational, point-of-care treatment decisions in pediatric patients with suspected raised ICP undergoing intensive care.

Introduction The erector spinae plane block (ESPB) is a newer fascial plane block which has been broadly applied for postoperative analgesia after various surgeries, but the effectiveness in these populations is not well established. Evidence acquisition A systematic database search was conducted in PubMed, PMC, Embase, and Scopus for randomized controlled trials (RCTs) comparing ESPB with control, placebo, or other blocks. The primary outcome was intravenous opioid consumption in milligram morphine equivalents 24 h after surgery. Standardized mean differences (SMDs) with 95% confidence intervals (CI) were calculated using a randomeffects model. Evidence synthesis A total of 29 RCTs were included. An analysis was conducted by subgroups differentiated by surgery type, 'no block' vs. ESPB, and other blocks vs. ESPB. ESPB was effective in reducing opioid consumption against no block for breast surgery (SMD -1.13; CI 95%), thoracic surgery (SMD -3.00; CI 95%), and vertebral surgery (SMD -1.78; CI 95%). ESPB was effective against alternative blocks for breast surgery (vs. paravertebral, SMD -1.07; CI 95%) and abdominal surgery (SMD -1.77; CI 95%). ESPB showed moderate effect in thoracic surgery against paravertebral (SMD 0.58; CI 95%) and against no block in abdominal surgery (SMD 0.80; CI 95%). In only one case did ESPB perform worse than another block: vs. PECS block for breast surgery (SMD 1.66; CI 95%). Conclusions ESPB may be a useful addition to the multimodal analgesic regimen for a variety of surgeries especially when the alternative is no block. Unanswered questions include determining of the mechanism of action, refining of the EPSB technique, and establishing recommended local anesthetic dose and volume.

This study aimed to investigate DNA methylation levels in patients undergoing major breast surgery under opioid-based general anesthesia. Blood samples were collected from eleven enrolled patients, before, during and after anesthesia. PBMC were isolated and global DNA methylation levels as well as DNA methyltransferase (DNMT) and cytokine gene expression were assessed. DNA methylation levels significantly declined by 26%, reversing the direction after the end of surgery. Likewise, DNMT1a mRNA expression was significantly reduced at all time points, with lowest level of −68%. DNMT3a and DNMT3b decreased by 65 and 71%, respectively. Inflammatory cytokines IL6 and TNFα mRNA levels showed a trend for increased expression at early time-points to end with a significant decrease at 48 h after surgery. This exploratory study revealed for the first time intraoperative global DNA hypomethylation in patients undergoing major breast surgery under general anesthesia with fentanyl. The alterations of global DNA methylation here observed seem to be in agreement with DNMTs gene expression changes. Furthermore, based on perioperative variations of IL6 and TNFα gene expression, we hypothesize that DNA hypomethylation may occur as a response to surgical stress rather than to opiate exposure.

We introduce and study the maximal unipotent finite quotient for algebraic group schemes in positive characteristics. Applied to Picard schemes, this quotient encodes unusual torsion. We construct integral Fano threefolds where such unusual torsion actually appears. The existence of such threefolds is surprising, because the torsion vanishes for del Pezzo surfaces. Our construction relies on the theory of exceptional Enriques surfaces, as developed by Ekedahl and Shepherd-Barron., Comment: 29 pages; minor changes

The severe acute respiratory syndrome coronavirus SARS-CoV2 is spreading over millions of people worldwide, leading to thousands of deaths, even among the healthcare providers. Italy has registered the deaths of 337 physicians and more than 200 nurses as of March 14, 2021. Anesthesiologists are at higher risk as they are the care providers in both ICU and operating rooms.Although the vaccination of healthcare providers has been the prioirity, physicians are still continually exposed to the virus and potentially risk contagion and must thus protect themselves and their patients from the risks of infection while providing the best care to their surgical patients.Regional anesthesia allows for a reduction in airway manipulation, reducing environmental contamination as a result. Furthermore, regional anesthesia reduces the opioid requirements as well as the muscle paralysis due to muscle-relaxants and should be recommended whenever possible in COVID-19 patients. Our aim is to evaluate the advantages and criticisms of regional anesthesia in the management of surgical patients in the pandemic age.

The importance of fetal surveillance during pregnancy is worldwide accepted since its peculiar ability to anticipate fetal distress under a variety of conditions. The novel frontier in the field of remote fetal monitoring relies on a continuous and everyday-monitoring of fetal wellbeing. As a consequence, fECG monitoring systems have seen a net increase in popularity in the recent years. In this paper, we propose a novel algorithm for the detection of fECG and we validated its performances by testing it on an open source collection of 75 annotated fECG traces. Our results show the reliability of the proposed methodology in extracting fECG and deriving an estimate of fHR.

Building on the work of Mukai, we explore the birational geometry of the moduli spaces $$M_{S,L}$$ of semistable rank two torsion-free sheaves, with $$c_1=-K_S$$ and $$c_2=2$$ , on a polarized degree one del Pezzo surface (S, L); this is related to the birational geometry of the blow-up X of $$\mathbb {P}^4$$ in 8 points. Our analysis is explicit and is obtained by looking at the variation of stability conditions. Then we provide a careful investigation of the blow-up X and of the moduli space $$Y=M_{S,-K_S}$$ , which is a remarkable family of smooth Fano fourfolds. In particular we describe the relevant cones of divisors of Y, the group of automorphisms, and the base loci of the anticanonical and bianticanonical linear systems.

We study the connected algebraic groups acting on Mori fibrations $X \to Y$ with $X$ a rational threefold and $\mathrm{dim}(Y) \geq 1$. More precisely, for these fibre spaces we consider the neutral component of their automorphism groups and study their equivariant birational geometry. This is done using, inter alia, minimal model program and Sarkisov program and allows us to determine the maximal connected algebraic subgroups of $\mathrm{Bir}(\mathbb{P}^3)$, recovering most of the classification results of Hiroshi Umemura in the complex case., 85 pages, final version

BACKGROUNDPerioperative regional anaesthesia may protect from persistent postsurgical pain (PPSP) and improve outcome after total knee arthroplasty (TKA).OBJECTIVESAim of this study was to evaluate the impact of regional anaesthesia on PPSP and long-term functional outcome after TKA.DESIGNA web-base

There are contrasting positions concerning the benefit-risk ratio of acetaminophen use for osteoarthritis (OA)-related pain. To clarify the effectiveness of acetaminophen or acetaminophen-codeine combinations according to their regimen of use, we evaluated whether being a regular user (adherent) of these medications decreased the occurrence of rescue therapy with non-steroidal anti-inflammatory drugs (NSAIDs).Using the Health Search IMS Health Longitudinal Patient Database, we formed a cohort of patients aged ≥18 years and newly treated with acetaminophen or acetaminophen-codeine combinations for OA between 1 January 2001 and 31 December 2013. These patients were followed up for one year in which they were categorized as regular or irregular users of these medications according to a variable medication possession ratio (VMPR) ≥ 50% or lower. We operationally defined the rescue therapy as the use of any NSAIDs prescribed for OA-related pain.Overall, 40,029 patients (69.5% females; mean age: 68 ± 13.57) treated with acetaminophen or acetaminophen-codeine combinations formed the cohort. After the first year of treatment, regular users showed a statistically significantly lower risk of being prescribed with rescue therapy with NSAIDs (OR = 0.89; 95% CI 0.84-0.96).These findings show that regular use of acetaminophen or acetaminophen-codeine combinations may reduce the need for NSAIDs to treat OA-related pain.

Objective: A noninvasive intracranial pressure (ICP) estimation method is proposed that incorporates a model-based approach within a probabilistic framework to mitigate the effects of data and modeling uncertainties. Methods: A first-order model of the cerebral vasculature relates measured arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) to ICP. The model is driven by the ABP waveform and is solved for a range of mean ICP values to predict the CBFV waveform. The resulting errors between measured and predicted CBFV are transformed into likelihoods for each candidate ICP in two steps. First, a baseline ICP estimate is established over five data windows of 20 beats by combining the likelihoods with a prior distribution of the ICP to yield an a posteriori distribution whose median is taken as the baseline ICP estimate. A single-state model of cerebral autoregulatory dynamics is then employed in subsequent data windows to track changes in the baseline by combining ICP estimates obtained with a uniform prior belief and model-predicted ICP. For each data window, the estimated model parameters are also used to determine the ICP pulse pressure. Results: On a dataset of thirteen pediatric patients with a variety of pathological conditions requiring invasive ICP monitoring, the method yielded for mean ICP estimation a bias (mean error) of 0.6 mmHg and a root-mean-squared error of 3.7 mmHg. Conclusion: These performance characteristics are well within the acceptable range for clinical decision making. Significance: The method proposed here constitutes a significant step towards robust, continuous, patient-specific noninvasive ICP determination.

Photodynamic therapy (PDT) is a clinically approved treatment that exerts a selective cytotoxic activity toward cancer cells. The procedure involves the administration of a photosensitizer drug followed by its activation by visible light. In the presence of oxygen, a series of events lead to tumor cell death. PDT releases different cell signals, some of these lead to death while others can lead to survival. The surviving or resistant cells contribute to the recurrence of tumors after treatment, from which the necessity to understand this molecular response induced by PDT arises. It has been shown that both Heat Shock Proteins (HSPs) and autophagy promote PDT resistance. Moreover, both of them can be stimulated by PDT treatment. However, the molecular interplay between HSPs and autophagy in the photodynamic therapy context is poorly understood. We studied whether PDT induces autophagic activity through HSPs. We demonstrated that PDT promoted HSP27 expression, which in turn triggered autophagic cell survival as well as inhibited apoptosis in colon cancer cells. In addition, an overexpression of the HSP27/autophagy axis was observed in skin carcinoma cells resistant to PDT.

• Chronic pain afflicts approximately 20% of the adult population worldwide. • Gender is one of the critical factors influencing the experience of pain. • Women report more severe levels of pain and chronic pain than men. • The response to pain therapy appears to be gender-related. • Sex hormones, endogenous opioid function, genetic factors, and psychosocial mechanisms contribute to gender differences in pain.

Introduction: Intravenous (I.V.) morphine administered through a patient-controlled system currently represents the gold standard treatment for moderate to severe acute postoperative pain. To fix the limitations showed by the available I.V. patient-controlled analgesia (PCA) systems that may restrict its use in the clinical practice a needle-free, iontophoretic, fentanyl patient-controlled transdermal system has been developed and recently approved by the United States Food and Drug Administration (FDA) and by the European Medicines Agency (EMA).Areas covered: This review aims at describing the technology, pharmacology and clinical efficacy of fentanyl iontophoretic transdermal system (ITS) in the treatment of acute pain. A literature search was conducted in the PUBMED database using the term fentanyl iontophoretic transdermal system through September 2015 and results from the main clinical trials are discussed.Expert opinion: In 2015, the appropriate treatment of acute pain after surgery is still a challenge and it represents a primary goal in the care of the surgical patient. When regional analgesia techniques are not applicable and systemic analgesia is required, patient controlled systems represent the standard of care for opioid administration. The fentanyl ITS presents several potential advantages compared to the currently used PCA devices. In particular, it does not require intravenous lines and eliminates the potential for drug administration errors, observed with manually programmed standard PCA devices. Nevertheless, further studies are needed to address eventual inter-individual variability especially for opioid tolerant patients.

The monitoring of intracranial pressure (ICP) is indicated for diagnosing and guiding therapy in many neurological conditions. Current monitoring methods, however, are highly invasive, limiting their use to the most critically ill patients only. Our goal is to develop and test an embedded device that performs all necessary mathematical operations in real-time for noninvasive ICP (nICP) estimation based on a previously developed model-based approach that uses cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) waveforms.The nICP estimation algorithm along with the required preprocessing steps were implemented on an NXP LPC4337 microcontroller unit (MCU). A prototype device using the MCU was also developed, complete with display, recording functionality, and peripheral interfaces for ABP and CBFV monitoring hardware.The device produces an estimate of mean ICP once per minute and performs the necessary computations in 410 ms, on average. Real-time nICP estimates differed from the original batch-mode MATLAB implementation of theestimation algorithm by 0.63 mmHg (root-mean-square error).We have demonstrated that real-time nICP estimation is possible on a microprocessor platform, which offers the advantages of low cost, small size, and product modularity over a general-purpose computer. These attributes take a step toward the goal of real-time nICP estimation at the patient's bedside in a variety of clinical settings.

Our objective was to develop, deploy, and test a data-acquisition system for the reliable and robust archiving of high-resolution physiological waveform data from a variety of bedside monitoring devices, including the GE Solar 8000i patient monitor, and for the logging of ancillary clinical and demographic information.The data-acquisition system consists of a computer-based archiving unit and a GE Tram Rac 4A that connects to the GE Solar 8000i monitor. Standard physiological front-end sensors connect directly to the Tram Rac, which serves as a port replicator for the GE monitor and provides access to these waveform signals through an analog data interface. Together with the GE monitoring data streams, we simultaneously collect the cerebral blood flow velocity envelope from a transcranial Doppler ultrasound system and a non-invasive arterial blood pressure waveform along a common time axis. All waveform signals are digitized and archived through a LabView-controlled interface that also allows for the logging of relevant meta-data such as clinical and patient demographic information.The acquisition system was certified for hospital use by the clinical engineering team at Boston Medical Center, Boston, MA, USA. Over a 12-month period, we collected 57 datasets from 11 neuro-ICU patients. The system provided reliable and failure-free waveform archiving. We measured an average temporal drift between waveforms from different monitoring devices of 1 ms every 66 min of recorded data.The waveform acquisition system allows for robust real-time data acquisition, processing, and archiving of waveforms. The temporal drift between waveforms archived from different devices is entirely negligible, even for long-term recording.

Background The purpose of this study was to determine whether oral prolonged-release oxycodone-naloxone combination (OXN) could provide equivalent analgesia and a side-effect profile similar to intravenous morphine patient-controlled analgesia (IVPCA) for the control of pain in the immediate postoperative period after total knee replacement (TKR). Methods All patients received a sciatic nerve block with 0.3% ropivacaine 15 mL, femoral nerve block with 0.5% ropivacaine 20 mL, spinal anesthesia and postoperative continuous femoral nerve infusion (ropivacaine 0.2% 4 mL/h). After surgery, patients were randomly allocated to receive either 10 +10 +5 mg controlled release OXN oral administration 12 hourly or IVPCA with morphine (2 mg bolus, no basal infusion). The primary outcome was the average rest and dynamic pain for the first 48 h postoperatively. Secondary outcomes were: post operative nausea vomiting (PONV) and the total morphine consumption. Results OXN group experienced better pain control at rest during the first (0.89±1.54 vs. 1.27±1.82, P=0.0019) and second (1.03±1.69 vs. 1.65±2.05, P=0.0006) postoperative period. There was no statistically significant difference in pain score during movement between the two groups. The secondary outcome measures showed no significant differences in the total morphine consumption (12.04±1.1 vs. 11.46±3.7 mg, P=0.20) or PONV (0.6±0.8 vs. 0.8±1.0, P=0.40). Conclusions This study show that in the immediate postoperative period after TKR, the patients receiving oral prolonged-release OXN experienced the same to better pain control than those receiving morphine IVPCA, with a similar degree of PONV.

Objectives: Our objective was to develop, deploy, and test a data-acquisition system for the reliable and robust archiving of high-resolution physiological waveform data from a variety of bedside monitoring devices, including the GE Solar 8000i patient monitor, and for the logging of ancillary clinical and demographic information.

We settle a question that originates from results and remarks by Koll\'ar on extremal ray in the minimal model program: In positive characteristics, there are no Mori fibrations on threefolds with only terminal singularities whose generic fibers are geometrically non-normal surfaces. To show this we establish some general structure results for del Pezzo surfaces over imperfect ground fields. This relies on Reid's classification of non-normal del Pezzo surfaces over algebraically closed fields, combined with a detailed analysis of geometrical non-reducedness over imperfect fields of p-degree one., Comment: 71 pages, minor changes, to appear in Trans. Amer. Math. Soc

Pain is the most common symptom reported by trauma patients entering the Emergency Department. Treatment has a crucial role in trauma, since adequate pain management leads not only to increased patient comfort and satisfaction, but also to reduced morbidity (such as pulmonary complications or thromboembolic events), shorter length of stay, and improved long-term outcomes. Unfortunately, multiple studies have reported that trauma-related pain is still inadequately controlled. Loco-regional anesthesia, e.g., peripheral nerve blocks, is emerging as an important technique that can be applied at the patient admission to the Emergency Department, and maintained through the perioperative setting. Regional anesthesia can become the first choice of analgesia in patients with isolated orthopedic injuries and burning injuries because this technique is devoid of many adverse effects associated with systemic opioids. Brachial plexus blocks can provide excellent analgesia for upper extremity trauma; lumbar plexus block and sciatic nerve block, both performed at different sites, can be used for lower extremity fractures, while epidural, paravertebral, intercostal, and interpleural block can provide analgesia for thoracic trauma. Some peculiar features of the trauma patients, such as acute blood loss, trauma associated coagulopathy, and the threat of compartment syndrome, must be kept in mind and pose an extra challenge to the choice of the optimal pain management technique.

Recent studies show that the risk of cardiovascular adverse events for certain traditional non-steroidal anti-inflammatory drugs (NSAIDs) is similar to that of rofecoxib. While these results are focused on ischemic cardiomyopathy, there is little evidence concerning the risk of ischemic stroke/transient ischemic attack and hemorrhagic stroke. Additionally, there is no information on nimesulide and ketoprofen, the most frequently prescribed NSAIDs in Italy, along with diclofenac. This study aims to determine whether the use of NSAIDs is associated with an increased risk of cerebrovascular events in Italy. We performed a case-control analysis nested in a cohort of patients with osteoarthritis between 2002 and 2011 who were newly treated with NSAIDs. The patients were followed until December 31, 2012. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI) of cerebrovascular events (index date) associated with current (until 30 days before the index date), recent (31-365 days) and past (>365 days) use of NSAIDs. Within a cohort of 29,722 patients, 1566 cases (1546 matched with controls) were identified (incidence rate = 11.0/1000 person-years). The overall rate of cerebrovascular event was not elevated with current NSAIDs overall when compared with past use. Among individual NSAIDs, diclofenac and ketoprofen were the molecules significantly associated with an increased rate of cerebrovascular events (OR = 1.53; 95% CI 1.04-2.24; OR = 1.62; 95% CI 1.02-2.58, respectively). The most frequent event was hemorrhagic stroke following the use of ketoprofen (OR = 2.09; 95% CI 1.05-4.15). Diclofenac and ketoprofen seemed to increase the risk of cerebrovascular events. These findings might influence the choice of NSAIDs according to patient characteristics.

The increasing and widespread use of direct oral anticoagulants (DOACs) demands guidelines and experts' consensus for their rational and safe use, especially in certain situations for which there is no evidence-based consensus, such as the periprocedural setting. Rivaroxaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF) and for treatment and prevention of venous thromboembolism (VTE) in major orthopedic surgery. This article is addressed to all the clinicians involved in the periprocedural approach of patients treated with rivaroxaban, with the aim to give practical recommendations to improve patients' management during and after surgery.This article is based on a consensus of specialists involved in anticoagulant treatment and in periprocedural setting, including experts in thrombosis, cardiologists, internists, clinical pathologists and anesthesiologists. The authors performed a review of the literature and expressed statements based on the results of the review as well as on personal experience.Rivaroxaban is a safe and effective drug that simplifies management of anticoagulation also in patients undergoing invasive procedures. However, periprocedural management could be challenging and physicians must carefully balance the risk of bleeding and the risk of thrombosis.

Objective.This study used a new method called Acceleration (or Deceleration) Phase-Rectified Slope, APRS (or DPRS) to analyze computerized Cardiotocographic (cCTG) traces in intrauterine growth restriction (IUGR), in order to calculate acceleration- and deceleration-related fluctuations of the fetal heart rate, and to enhance the prediction of neonatal outcome.Method.Cardiotocograms from a population of 59 healthy and 61 IUGR fetuses from the 30th gestation week matched for gestational age were included. APRS and DPRS analysis was compared to the standard linear and nonlinear cCTG parameters. Statistical analysis was performed through thet-test, ANOVA test, Pearson correlation test and receiver operator characteristic (ROC) curves (p<0,05).Results.APRS and DPRS showed high performance to discriminate between Healthy and IUGR fetuses, according to gestational week. A linear correlation with the fetal pH at birth was found in IUGR. The area under the ROC curve was 0.865 for APRS and 0.900 for DPRS before the 34th gestation week.Conclusions.APRS and DPRS could be useful in the identification and management of IUGR fetuses and in the prediction of the neonatal outcome, especially before the 34th week of gestation.