Genetics in Parkinson's disease, state-of-the-art and future perspectives.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is clinically characterized by the presence of motor (bradykinesia, rigidity, rest tremor and postural instability) and non-motor symptoms (cognitive impairment, autonomic dysfunction, sleep disorders, depression and hyposmia). The aetiology of PD is unknown except for a small but significant contribution of monogenic forms. SOURCES OF DATA: No new data were generated or analyzed in support of this review. AREAS OF AGREEMENT: Up to 15% of PD patients carry pathogenic variants in PD-associated genes. Some of these genes are associated with mendelian inheritance, while others act as risk factors. Genetic background influences age of onset, disease course, prognosis and therapeutic response. AREAS OF CONTROVERSY: Genetic testing is not routinely offered in the clinical setting, but it may have relevant implications, especially in terms of prognosis, response to therapies and inclusion in clinical trials. Widely adopted clinical guidelines on genetic testing are still lacking and open to debate. Some new genetic associations are still awaiting confirmation, and selecting the appropriate genes to be included in diagnostic panels represents a difficult task. Finally, it is still under study whether (and to which degree) specific genetic forms may influence the outcome of PD therapies. GROWING POINTS: Polygenic Risk Scores (PRS) may represent a useful tool to genetically stratify the population in terms of disease risk, prognosis and therapeutic outcomes. AREAS TIMELY FOR DEVELOPING RESEARCH: The application of PRS and integrated multi-omics in PD promises to improve the personalized care of patients.

Effects of competitive physical activity on serum irisin levels and bone turnover markers.

BACKGROUND: Irisin, a myokine, is a polypeptide derived from the cleavage of the extracellular domain of fibronectin domain-containing protein 5, a receptor that is present on different tissues (skeletal muscle, pericardium, myocardium, and brain), whose functions are not yet fully defined. PURPOSE: The main aim of our study was to evaluate the effect of competitive physical activity on serum irisin levels and bone turnover markers. METHODS: Fifteen male footballers and an equal number of subjects of the same age and gender, but with a predominantly sedentary lifestyle, had their serum levels of irisin and bone turnover markers measured. Bone mineral status was evaluated in both groups by quantitative bone ultrasound of the calcaneus. In addition, only in footballers, biochemical analyses were repeated after 3 months. RESULTS: We did not observe significant differences in the serum levels of calcium, phosphorus, and parathyroid hormone between the two groups. The footballers had significantly higher quantitative bone ultrasound, 25-OH vitamin D, and creatinine values than the controls. There were also no significant differences in the bone alkaline phosphatase, carboxy-terminal telopeptide of type I collagen, osteoprotegerin, sclerostin or Dkk-1 values, while the irisin levels (+ 89%, p < 0.001) and RANKL were significantly higher in the footballers compared to those in the controls. CONCLUSION: Our study shows that footballers have significantly higher serum irisin values than the general population. Irisin could be the "trait d'union" between bone health and physical activity.

Chronic pain after breast surgery: incidence, associated factors, and impact on quality of life, an observational prospective study.

BACKGROUND: Chronic pain after breast surgery (CPBS) has a disabling impact on postoperative health status. Mainly because of the lack of a clear definition, inconsistency does exist in the literature concerning both the actual incidence and the risk factors associated to CPBS. The aim of this prospective, observational study is to describe the incidence of and risk factors for CPBS, according to the definition provided by the IASP taskforce. The impact of CPBS on patients' function and quality of life is also described. METHODS: Women aged 18+ undergoing oncological or reconstructive breast surgery from Jan until Apr 2018 at the Breast Unit of Careggi Hospital (Florence, Italy) were prospectively observed. Postoperative pain was measured at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 3 months (CPBS) after surgery. Preoperative, intraoperative, and postoperative factors were compared in CPBS and No-CPBS groups through multivariate logistic regression analysis. RESULTS: Among the 307 patients considered in this study, the incidence of CPBS was 28% [95% CI 23.1-33.4%]. Results from the logistic regression analysis suggest that axillary surgery (OR [95% CI], 2.99 [1.13-7.87], p = 0.03), preoperative use of pain medications (OR [95% CI], 2.04 [1.20-3.46], p = 0.01), and higher dynamic NRS values at 6 h postoperatively (OR [95% CI], 1.28 [1.05-1.55], p = 0.01) were all independent predictors for CPBS. CONCLUSIONS: Chronic pain after breast surgery is a frequent complication. In our cohort, long-term use of analgesics for pre-existing chronic pain, axillary surgery, and higher dynamic NRS values at 6 h postoperatively were all factors associated with increased risk of developing CPBS. The possibility to early detect persistent pain, particularly in those patients at high risk for CPBS, might help physicians to more effectively prevent pain chronicisation. TRIAL REGISTRATION: ClinicalTrials.gov registration NCT04309929 .

Effects of psychological interventions on anxiety and pain in patients undergoing major elective abdominal surgery: a systematic review.

A maladaptive response to surgical stress might lead to postoperative complications. A multidisciplinary approach aimed at controlling the surgical stress response may reduce procedural complications and improve patients' quality of life in the short and long term. Several studies suggest that psychological interventions may interact with the pathophysiology of surgical stress response, potentially influencing wound repair, innate and adaptive immunity, inflammation, perception of pain, and patients' mood. The aim of this systematic review is to summarise the effects of perioperative psychological interventions on surgical pain and/or anxiety in adult patients scheduled for elective general abdominal and/or urologic surgery.We conducted a systematic review of controlled clinical trials and observational studies involving psychological interventions for adult patients scheduled for elective general abdominal and/or urologic surgery. Only studies reporting pain and/or anxiety among outcome measures were included in the systematic review. The following psychological interventions were considered: (1) relaxation techniques, (2) cognitive-behavioural therapies, (3) mindfulness, (4) narrative medicine, (5) hypnosis and (6) coping strategies.We examined 2174 papers. Among these, 9 studies were considered eligible for inclusion in this systematic review (1126 patients cumulatively): 8 are randomised controlled trials and 1 is an observational prospective pre/post study.Psychological characteristics widely influence the pathophysiological mechanisms underlying the neuroendocrine and inflammatory response to surgical stress, potentially interfering with surgical outcomes. Psychological interventions are technically feasible and realistically applicable perioperatively during abdominal and/or urologic surgery; they influence the pathophysiological mechanisms underlying maladaptive surgical stress response and might have positive effects on patients' surgical outcomes, such as pain and anxiety.

Pathophysiology and Management of Type 2 Diabetes Mellitus Bone Fragility.

Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of bone fragility fractures compared to nondiabetic subjects. This increased fracture risk may occur despite normal or even increased values of bone mineral density (BMD), and poor bone quality is suggested to contribute to skeletal fragility in this population. These concepts explain why the only evaluation of BMD could not be considered an adequate tool for evaluating the risk of fracture in the individual T2DM patient. Unfortunately, nowadays, the bone quality could not be reliably evaluated in the routine clinical practice. On the other hand, getting further insight on the pathogenesis of T2DM-related bone fragility could consent to ameliorate both the detection of the patients at risk for fracture and their appropriate treatment. The pathophysiological mechanisms underlying the increased risk of fragility fractures in a T2DM population are complex. Indeed, in T2DM, bone health is negatively affected by several factors, such as inflammatory cytokines, muscle-derived hormones, incretins, hydrogen sulfide (H2S) production and cortisol secretion, peripheral activation, and sensitivity. All these factors may alter bone formation and resorption, collagen formation, and bone marrow adiposity, ultimately leading to reduced bone strength. Additional factors such as hypoglycemia and the consequent increased propensity for falls and the direct effects on bone and mineral metabolism of certain antidiabetic medications may contribute to the increased fracture risk in this population. The purpose of this review is to summarize the literature evidence that faces the pathophysiological mechanisms underlying bone fragility in T2DM patients.

SARS-CoV-2 and COVID-19: From the Bench to the Bedside.

First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe, and the United States. COVID-19 is a new clinical syndrome, characterized by respiratory symptoms with varying degrees of severity, from mild upper respiratory illness to severe interstitial pneumonia and acute respiratory distress syndrome, aggravated by thrombosis in the pulmonary microcirculation. Three main phases of disease progression have been proposed for COVID-19: an early infection phase, a pulmonary phase, and a hyperinflammation phase. Although current understanding of COVID-19 treatment is mainly derived from small uncontrolled trials that are affected by a number of biases, strong background noise, and a litany of confounding factors, emerging awareness suggests that drugs currently used to treat COVID-19 (antiviral drugs, antimalarial drugs, immunomodulators, anticoagulants, and antibodies) should be evaluated in relation to the pathophysiology of disease progression. Drawing upon the dramatic experiences taking place in Italy and around the world, here we review the changes in the evolution of the disease and focus on current treatment uncertainties and promising new therapies.

Sleep duration and architecture in non-intubated intensive care unit patients: an observational study.

OBJECTIVE/BACKGROUND: Sleep disturbances are very common and associated with severe complications in patients admitted to intensive care units (ICU). Commonly, sedatives like propofol or benzodiazepines have been demonstrated to increase sleep duration but worsen sleep architecture. Dexmedetomidine seems to positively affect both sleep aspects. PATIENTS/METHODS: The present study aimed to investigate sleep characteristics in non-intubated patients admitted to intensive care unit. The subgroups consisted of those without sedation (NO-DEX), and those which received dexmedetomidine infusion (DEX), titrated to a Richmond Agitation-Sedation Scale target of -1/-2, were also explored. An auto-staged electroencephalographer was used to measure sleep duration and architecture. The Richard-Campbell-Sleep questionnaire was administered to all patients. RESULTS: A multivariate analysis conducted in the overall population showed that dexmedetomidine infusion was the only variable independently associated with N2 increase (p < 0.001). DEX (n = 36) versus NO-DEX (n = 36) group showed longer N2 stage [68.9% (57.5-80.9) versus 49.5% [35.7-61.4]; p < 0.0003]; longer Total Sleep Time [6.5 h (5.7-7.7) versus 3.4 h (1.8-4.9); p < 0.0001, and higher Sleep Efficiency [84.2% (71.3-92.6) versus 47.7% (23.4-60.9); p < 0.0001]; shorter N1 (percentage of Total Sleep Time) [10.5% (7.8-20.0) and 38.8% (25.6-50.3); p < 0.0001]; longer N3 stage [13.6% (1.9-23.3) versus 4.3% (0.4-14.0); p = 0.058]; fewer Cortical Arousals [15 episodes/hour (8.1-24.6) versus 48.7 episodes/hour (29.7-80.4); p < 0.0001]. The questionnaire showed better values in DEX-group in all explored items (p < 0.0001). CONCLUSIONS: Abnormal sleep is common in intensive care unit patients who have not received sedation. Dexmedetomidine, titrated to reach an appropriate sedation level, may optimize sleep duration and architecture.

Validation of END-of-life ScorING-system to identify the dying patient: a prospective analysis.

BACKGROUND: The "END-of-Life ScorING-System" (ENDING-S) was previously developed to identify patients at high-risk of dying in the ICU and to facilitate a practical integration between palliative and intensive care. The aim of this study is to prospectively validate ENDING-S in a cohort of long-term critical care patients. MATERIALS AND METHODS: Adult long-term ICU patients (with a length-of-stay> 4 days) were considered for this prospective multicenter observational study. ENDING-S and SOFA score were calculated daily and evaluated against the patient's ICU outcome. The predictive properties were evaluated through a receiver operating characteristic (ROC) analysis. RESULTS: Two hundred twenty patients were enrolled for this study. Among these, 21.46% died during the ICU stay. ENDING-S correctly predicted the ICU outcome in 71.4% of patients. Sensitivity, specificity, positive and negative predictive values associated with the previously identified ENDING-S cut-off of 11.5 were 68.1, 72.3, 60 and 89.3%, respectively. ROC-AUC for outcome prediction was 0.79 for ENDING-S and 0.88 for SOFA in this cohort. CONCLUSIONS: ENDING-S, while not as accurately as in the pilot study, demonstrated acceptable discrimination properties in identifying long-term ICU patients at very high-risk of dying. ENDING-S may be a useful tool aimed at facilitating a practical integration between palliative, end-of-life and intensive care. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02875912; First registration August 4, 2016.

Caspofungin PK in critically ill patients after the first and fourth doses: suggestions for therapeutic drug monitoring?

We describe caspofungin pharmacokinetics (PK) after the first and fourth doses in 20 critically ill septic patients. Monte Carlo simulation was used to analyze the probability of target attainment (PTA) (AUC/MIC > 865) for Candida spp. Caspofungin concentrations were analyzed by HPLC in plasma and urine. A great variability in PK parameters was observed after both doses. Patients were divided in two groups according to their AUC values (AUC ≤ 75 mg h/L cut-off). In the low-AUC group Cmax, Cmin and AUC were lower, while Vd and Cl were higher than in the high-AUC group (p < 0.05, both at day 1 and 4). The mean 24-h urinary recovery of the drug was 8 ± 6.3% (day1) and 9.8 ± 6.3 (day4). Monte Carlo simulation analysis (0.03-1 mg/L MIC-range) showed that PTA was guaranteed only for MICs ≤ 0.03 mg/L in the low-AUC group, and for MICs ≤ 0.06 mg/L in the high-AUC group. No group had a PTA ≥ 90% for 0.125 mg/L MIC (the epidemiological cut-off). Mortality was higher in low-AUC group (p < 0.01). In our 'real-world' population, no clinical data can predict which patient will have lower, suboptimal caspofungin exposure, therefore we suggest TDM to optimize caspofungin therapy and reduce the risk of selecting resistances (CEAVC, 32366/2015; OSS.15.114, NCT03798600).

In-line filtration reduced phlebitis associated with peripheral venous cannulation: Focus on cost-effectiveness and patients' perspectives.

BACKGROUND: In a previous trial, in-line filtration significantly prevented postoperative phlebitis associated with short peripheral venous cannulation. This study aims to describe the cost-effectiveness of in-line filtration in reducing phlebitis and examine patients' perception of in-hospital vascular access management with and without in-line filtration. METHODS: We analysed costs associated with in-line filtration: these data were prospectively recorded during the previous trial. Furthermore, we performed a follow-up for all the 268 patients enrolled in this trial. Among these, 213 patients responded and completed 6 months after hospital discharge questionnaires evaluating the perception of and satisfaction with the management of their vascular access. RESULTS: In-line filtration group required 95.60€ more than the no-filtration group (a mean of € 0.71/patient). In terms of satisfaction with the perioperative management of their short peripheral venous cannulation, 110 (82%) and 103 (76.9%) patients, respectively, for in-line filtration and control group, completed this survey. Within in-line filtration group, 97.3% of patients were satisfied/strongly satisfied; if compared with previous experiences on short peripheral venous cannulation, 11% of them recognised in-line filtration as a relevant causative factor in determining their satisfaction. Among patients within the control group, 93.2% were satisfied/strongly satisfied, although up to 30% of them had experienced postoperative phlebitis. At the qualitative interview, they recognised no difference than previous experiences on short peripheral venous cannulation, and mentioned postoperative phlebitis as a common event that 'normally occurs' during a hospital stay. CONCLUSION: In-line filtration is cost-effective in preventing postoperative phlebitis, and it seems to contribute to increasing patient satisfaction and reducing short peripheral venous cannulation-related discomfort.

Tapentadol prolonged release in association with analgesic radiofrequency for the treatment of chronic lumbar radicular pain: an observational, prospective study.

OBJECTIVE: Chronic pain is frequently irreversible, representing a major health problem. A survey has shown that 19% of European adults experience chronic pain which is not adequately managed. Innovative interventional techniques for the treatment of chronic pain have been developed, as a further step beyond the three-layer WHO analgesic ladder. Among these techniques, continuous and pulsed radiofrequency (RF) are very effective in the management of radicular pain syndrome. Usually, these techniques are associated with a pharmacologic approach with a wide-spectrum analgesic. Tapentadol has a double mechanism of action, as a µ-opioid receptor agonism (MOR) and noradrenaline reuptake inhibitor (NRI), contributing synergistically to its analgesic efficacy on both nociceptive and neuropathic pain. PATIENTS AND METHODS: We aimed to test the efficacy of tapentadol prolonged release (PR) combined with pulsed RF in improving neuropathic symptoms and disability in 50 patients with moderate-to-severe chronic pain due to lumbar radiculopathy. RESULTS: The responders to treatment, showing at least a 30% reduction in pain intensity on the Numerical Rating Scale (NRS), were 38 (76%). Both average NRS at rest and during loading were statistically significantly reduced compared with baseline (p<0.0001). Other parameters investigated (sleep quality, neuropathic symptoms, the degree of disability) were all statistically better with tapentadol PR. Patients requiring RF intervention dropped dramatically from 98% at baseline to 10% at the end of the study (p<0.01). Adverse events were reported in 14 patients (28%), four of which required therapy discontinuation. However, patients' satisfaction and overall tolerability of tapentadol PR treatment were high. CONCLUSIONS: Tapentadol PR is effective in reducing pain intensity at rest and during loading, with a favorable safety and tolerability profile. Moreover, the use of tapentadol PR decreases the degree and severity of disability, as well as the intensity of neuropathic symptoms.

Trabecular bone score and quantitative ultrasound measurements in the assessment of bone health in breast cancer survivors assuming aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AIs) represent the first-line adjuvant therapy for hormone receptor-positive breast cancer (BC) women. AIs have been associated with an increased rate of fractures. The aim of our study was to investigate trabecular bone score (TBS) and bone quantitative ultrasound (QUS) measurements as bone quality surrogates in AIs users. METHODS: Sixty postmenopausal BC women starting AIs and forty-two controls (mean age 61.64 ± 8.33 years) were considered. Bone mineral density (BMD) at lumbar spine and femoral neck and TBS were measured by DXA; QUS-derived Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), and Ultrasound Bone Profile Index (UBPI) were assessed at phalangeal site; morphometric vertebral fractures (Vfx) by X-ray, serum bone-specific alkaline phosphatase (BSAP), and C-telopeptide of type 1 collagen (CTX) were also evaluated. RESULTS: After 18 months, changes of TBS vs baseline were significantly different between AIs group and controls [Δ TBS - 2.2% vs - 0.4%, respectively, p = 0.001]. AD-SoS, BTT and UBPI values decreased only in AIs' group (- 3.7%, - 6.45%, -8.5%, vs baseline, respectively, pall < 0.001). 3 Vfx occurred in AIs users and were associated with the greater TBS and AD-SoS modifications. In the AIs' group, ΔTBS was associated with ΔAD-SoS (r = 0.58, p < 0.001) and ΔUBPI (r = 0.415, p = 0.001), but not with ΔBMD. Moreover, ΔTBS was independently predicted by ΔAD-SoS, after correcting for BMD, CTX and BSAP level changes (ß = 0.37, SE = 2.44, p < 0.001). CONCLUSIONS: TBS and phalangeal QUS provide useful information related to bone quality in AI-treated BC survivors and could be considered for fracture risk evaluation.

oXirisNet Registry: A Prospective, National Registry on the oXiris Membrane.

Worldwide, the widespread use of extracorporeal blood purification therapies (EBPTs) is progressively increasing in everyday clinical practice, particularly in critical care settings. The efficacy of EBPTs on removal of inflammatory mediators is already well established in the literature. Nonetheless, clinical research is particularly cumbersome in this setting, and many clinical trials aiming at exploring the effect of EBPTs on outcomes have failed in demonstrating consistent results regarding 28-day- or hospital-mortality rates. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of EBPTs. The philosophy behind this Italian Registry is a renewal of the concept of "clinical research" in the field of EBPTs applied to critically ill, septic patients with or without acute kidney injury. The platform used for the registry - specifically designed for research purposes and fed by clinical data prospectively observed - promotes good practice with a positive and active interaction with the physician/researcher. This interaction has favorable real-time effects for the specific patient, providing "bed-side clinical feedbacks," similarly to the decision support system. Examples of these issues are bundles reminders, suggestions for drug adjustment according to the extracorporeal clearance, clinical calculator for body mass index, or mechanical ventilation setting. The platform-physician interaction has additional useful effects on the single utilizing center, providing "mid-term, center-specific clinical feedbacks." These generally consist of clusters of data taken over a certain period, for example, regarding patients' outcome, microbiological data, or use of disposable for EBPTs.

A comparison of two different concentrations and infusion rates of ropivacaine in perineural infusion administered at the same total dose for analgesia after foot and ankle surgery: a randomized, double blinded, controlled study.

BACKGROUND: Continuous popliteal nerve block is utilized for postoperative analgesia after foot and ankle surgery. Whether only the total dose of local anesthetic or the combination of concentration and volume determine the characteristics of a continuous popliteal nerve infusion remains currently unknown. We hypothesized a reduction of the incidence of insensate extremity in patients given ropivacaine 0.4% at 4 mL/h compared to patients given ropivacaine 0.2% at 8 mL/h. METHODS: Sixty-four patients scheduled for major foot and ankle surgery requiring a continuous popliteal catheter infusion for postoperative analgesia were studied. Thirty-three patients were randomized to receive a continuous popliteal nerve block with 0.2% (basal 8 mL/h) and thirty-one with 0.4% (basal 4 mL/h) ropivacaine, reaching the same total dose (16 mg/h). The primary outcome was the incidence of persistent sensory block in the distal sciatic nerve distributions in the postoperative period. Secondary outcomes were the incidence of motor block, NRS pain scores at rest in the postoperative period up to 48 hours after surgery, opioid use and related side effects, patients' satisfaction. RESULTS: The incidence of persistent sensory block was similar in patients given 0.2% and in patients receiving 0.4% ropivacaine. The incidence of motor block, postoperative pain scores at rest, use of oral opioids, side effects and patients' satisfaction with the quality of recovery were also similar in both groups. CONCLUSIONS: Our results suggest that local anesthetic total dose is the primary determinant of continuous popliteal perineural infusion effects.

An Observational Study of Cerebral Blood Flow Velocity Evaluation in the Prone Position During Posterior Lumbar Surgery.

BACKGROUND: Prone positioning (PP) is necessary for surgical access during posterior spine procedure. However, physiological changes occur in the PP. Typical findings are a decrease in arterial blood pressure and in cardiac output that could potentially lead to an alteration in cerebral perfusion. Therefore, we decided to study cerebral blood flow velocity (CBFV) with transcranial Doppler ultrasonography to evaluate the effect of the PP on cerebral hemodynamics. METHODS: Twenty-two patients undergoing spine surgery in the PP were studied. General anesthesia was induced using 250 µg of fentanyl, 2 mg/kg of propofol, and 0.1 mg/kg of vecuronium, and was maintained with 0.25%-0.5% isoflurane, 50% nitrous oxide in oxygen, continuous infusion of 100 µg/kg/min of propofol, 1.5 µg/kg/h of fentanyl, and 0.15 mg/kg/h of ketamine. Continuous invasive arterial blood pressure, heart rate, electrocardiogram, and end-tidal carbon dioxide were monitored. CBFV with transcranial Doppler in the middle cerebral artery was first measured with the patients under general anesthesia in the supine position. Patients were then placed in the PP and remained in this position throughout surgery. CBFV, end-tidal carbon dioxide, heart rate, and blood pressure were measured continuously for 75 minutes after initiation of PP. This coincided with surgical exposure and minimal blood loss. Data were analyzed every 15 minutes for statistical significant change over time. RESULTS: Mean arterial blood pressure decreased 15 minutes after the installation of the PP and onward, but this decrease was not statistically significant. CBFVsyst (the maximal CBFV during the systolic phase of a cardiac cycle) and CBFVmean (the time averaged value of the maximal velocity envelope over 1 cardiac cycle) did not vary at any time points. CBFVdiast (the CBFV just before the acceleration phase [systole] of the next waveform) was lower at T3 (30 minutes after PP) compared to T1 (value derived averaging the first measure in the PP with the ones at 5 and 10 minutes) (P = .01), and the pulsatility index was higher at T5 (60 minutes after PP) compared to T0 (baseline, patient supine under general anesthesia) (P = .04). Data were analyzed at specific time points (T0 and T1). This value was derived by computing an average of the CBFV values collected at the first measure in the PP and at 5 and 10 minutes thereafter: T2, 15 minutes after PP; T3, 30 minutes after PP; T4, 45 minutes after PP; T5, 60 minutes after PP; and T6, 75 minutes after PP. CONCLUSIONS: Our data on CBFV during PP for spine surgery demonstrate preservation of cerebral perfusion during stable systemic hemodynamic conditions. The present results do not allow us to determine whether the PP would be similarly tolerated with increasing length of surgery, variations in systemic hemodynamics, and in different patient populations.

In-Line Filtration Reduces Postoperative Venous Peripheral Phlebitis Associated With Cannulation: A Randomized Clinical Trial.

BACKGROUND: Peripheral venous cannulation is an everyday practice of care for patients undergoing anesthesia and surgery. Particles infused with intravenous fluids (eg, plastic/glass/drugs particulate) contribute to the pathogenesis of peripheral phlebitis. The aim of this study is to demonstrate the efficacy of in-line filtration in reducing the incidence of postoperative phlebitis associated with peripheral short-term vascular access. METHODS: In this controlled trial, 268 surgical patients were randomly assigned to in-line filtration and standard care (NCT03193827). The incidence of phlebitis (defined as visual infusion phlebitis [VIP] score, ≥2) within 48 hours was compared between the 2 groups, as well as the onset and severity of phlebitis and the reasons for removal of the cannula. The lifespan of venous cannulae was compared for the in-line filter and no-filter groups through a Kaplan-Meier curve. RESULTS: The incidence of phlebitis within 48 hours postoperatively was 2.2% and 26.9% (difference, 25% [95% confidence interval {CI}, 12%-36%]; odds ratio, 0.05 [0.01-0.15]), respectively, for the in-line filter and no-filter groups (P < .001). From 24 to 96 hours postoperatively, patients in the no-filter group had higher VIP scores than those in in-line filter group (P < .001). Venous cannulae in the in-line filter group exhibited prolonged lifespan compared to those in the no-filter group (P = .01). In particular, 64 (47.8%) of cannulae in the in-line filter group and 56 (41.8%) of those in the no-filter group were still in place at 96 hours postoperatively. At the same time point, patients with a VIP score <3 were 100% in the in-line filter group and only 50% for the no-filter group. In-line filtration was a protective factor for postoperative phlebitis (hazard ratio, 0.05 [95% CI, 0.014-0.15]; P < .0001) and cannula removal (hazard ratio, 0.7 [95% CI, 0.52-0.96]; P = .02). CONCLUSIONS: In-line filtration has a protective effect for postoperative phlebitis and prolongs cannula lifespan during peripheral venous cannulation in surgical patients.

The Valsalva manoeuvre versus tourniquet for venipuncture.

BACKGROUND: During ultrasound-guided cannulation, venous filling is required for venipuncture. Tourniquet with an elastic tube at the axilla is the most common method to induce venous stasis for cannulation of the deep veins of the arm. Although effective, this method might be associated with short- and long-term complications. Valsalva manoeuvre has been used to produce venous filling in other extrathoracic veins. The aim of this observational study is to demonstrate the effect of Valsalva manoeuvre in respect of the elastic tourniquet on venous distention during echography-guided cannulation of the deep veins of the arm. METHOD: Sixty-nine patients scheduled for cannulation of basilic or brachial vein were prospectively observed. Vein diameters were recorded at rest and after 10 s of Valsalva or tourniquet placement. RESULTS: The mean difference between basilic vein diameters during tourniquet and Valsalva manoeuvre was 0.006 mm (95% confidence interval = -inf, 0.09) with a standard deviation of 0.5 mm (95% confidence interval = 0.5, 0.7; p > 0.01). The mean difference between brachial vein diameters during tourniquet and Valsalva manoeuvre was 0.04 mm (95% confidence interval = -0.23, 0.15) with a standard deviation of 0.8 mm (95% confidence interval = 0.7, 0.9; p > 0.01). DISCUSSION: This increase in cross-sectional basilic and brachial vein diameters was not different to that obtained with the elastic tube tourniquet.

The New MIRUS System for Short-Term Sedation in Postsurgical ICU Patients.

OBJECTIVES: To evaluate the feasibility and safety of the MIRUS system (Pall International, Sarl, Fribourg, Switzerland) for sedation with sevoflurane for postsurgical ICU patients and to evaluate atmospheric pollution during sedation. DESIGN: Prospective interventional study. SETTING: Surgical ICU. February 2016 to December 2016. PATIENTS: Postsurgical patients requiring ICU admission, mechanical ventilation, and sedation. INTERVENTIONS: Sevoflurane was administered with the MIRUS system targeted to a Richmond Agitation Sedation Scale from -3 to -5 by adaptation of minimum alveolar concentration. MEASUREMENTS AND MAIN RESULTS: Data collected included Richmond Agitation Sedation Scale, minimum alveolar concentration, inspired and expired sevoflurane fraction, wake-up times, duration of sedation, sevoflurane consumption, respiratory and hemodynamic data, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment, and laboratory data and biomarkers of organ injury. Atmospheric pollution was monitored at different sites: before sevoflurane delivery (baseline) and during sedation with the probe 15 cm up to the MIRUS system (S1) and 15 cm from the filter-Reflector group (S2). Sixty-two patients were enrolled in the study. No technical failure occurred. Median Richmond Agitation Sedation Scale was -4.5 (interquartile range, -5 to -3.6) with sevoflurane delivered at a median minimum alveolar concentration of 0.45% (interquartile range, 0.4-0.53) yielding a mean inspiratory and expiratory concentrations of 0.79% (SD, 0.24) and 0.76% (SD, 0.18), respectively. Median awakening time was 4 minutes (2.2-5 min). Median duration of sevoflurane administration was 3.33 hours (2.33-5.75 hr), range 1-19 hours with a mean consumption of 7.89 mL/hr (SD, 2.99). Hemodynamics remained stable over the study period, and no laboratory data indicated liver or kidney injury or dysfunction. Median sevoflurane room air concentration was 0.10 parts per million (interquartile range, 0.07-0.15), 0.17 parts per million (interquartile range, 0.14-0.27), and 0.15 parts per million (interquartile range, 0.07-0.19) at baseline, S1, and S2, respectively. CONCLUSIONS: The MIRUS system is a promising and safe alternative for short-term sedation with sevoflurane of ICU patients. Atmospheric pollution is largely below the recommended thresholds (< 5 parts per million). Studies extended to more heterogeneous population of patients undergoing longer duration of sedation are needed to confirm these observations.

Quantitative ultrasound and DXA measurements in aromatase inhibitor-treated breast cancer women receiving denosumab.

PURPOSE: Denosumab has been proven to reduce fracture risk in breast cancer (BC) women under aromatase inhibitors (AIs). Quantitative ultrasound (QUS) provides information on the structure and elastic properties of bone. Our aim was to assess bone health by phalangeal QUS and by dual-energy X-ray absorptiometry (DXA), and to evaluate bone turnover in AIs-treated BC women receiving denosumab. METHODS: 35 Postmenopausal BC women on AIs were recruited (mean age 61.2 ± 4.5 years) and treated with denosumab 60 mg administered subcutaneously every 6 months. Phalangeal QUS parameters [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), Bone Transmission Time (BTT)] and DXA at lumbar spine and femoral neck were performed. Serum C-telopeptide of type 1 collagen (CTX) and bone-specific alkaline phosphatase (BSAP) were also measured. The main outcomes were compared with a control group not receiving denosumab (n = 39). RESULTS: In patients treated with denosumab, differently from controls, QUS and DXA measurements improved after 24 months, and a reduction of CTX and BSAP was detected at 12 and 24 months in comparison to baseline (P < 0.05). The percent changes (Δ) of QUS measurements were significantly associated with ΔBMD at femoral neck, and ΔCTX and ΔBSAP were associated with ΔBMD at lumbar spine (r = -0.39, P = 0.02; r = -0.49, P = 0.01, respectively). CONCLUSIONS: Denosumab preserves bone health as assessed by phalangeal QUS and DXA. Since inexpensive and radiation-free, phalangeal QUS may be considered in the follow-up of AIs-treated BC women receiving denosumab.

Organ dysfunction during continuous veno-venous high cut-off hemodialysis in patients with septic acute kidney injury: A prospective observational study.

BACKGROUND: Continuous veno-venous hemodialysis with high cut-off membranes (HCO-CVVHD) removes inflammatory mediators involved in organ dysfunction during sepsis. The aim of the present study was to assess the variations in SOFA score and identify early predictors of short-term mortality in a cohort of patients with septic shock, treated with HCO-CVVHD for acute kidney injury (AKI). METHODS: An observational prospective multicenter cohort study was conducted in four mixed medical-surgical ICUs. Thirty-eight patients with septic shock and AKI (KDIGO stage≥1) treated with HCO-CVVHD have been included in this study. Patients were divided into Survivors and non-Survivors according to mortality observed at 72nd hr of treatment. The variation of SOFA scores and clinical/biochemical parameters were described over time for the entire population and specifically for Survivors and non-Survivors. Similarly, circulating inflammatory mediators (as IL-6, TNF-a and IL-10) were described over time. A logistic regression analysis was used to identify the baseline clinical and biochemical parameters associated with 72 hrs-ICU mortality. RESULTS: Overall, the mean SOFA score was 12±3 at baseline, 10.9±3 at 6hrs, 9.8±3 at 12hrs, 8.9±3.3 at 24 hrs, and 8±3.5 at 48 hrs after HCO-CVVHD initiation; and 6.5±2.7 at 24 hrs and 6.6±3 at 48 hrs after HCO-CVVHD discontinuation. In the multivariate regression analysis, baseline serum lactate levels and AKI stage independently correlated with short-term mortality during HCO-CVVHD. A significant reduction was observed in circulating levels of TNFα and IL-6 among Survivors. CONCLUSIONS: SOFA score significantly decreased early after initiation of HCO-CVVHD in patients with septic AKI. Baseline lactate levels and the AKI stage resulted to be associated to 72 hrs-ICU-mortality.