Use of Fluoride as a Marker Solute to Quantify the Current Effective Delivered Dose in Continuous Renal Replacement Therapy: An "in vitro" Study.

BACKGROUND: The current effective delivered dose is a quality indicator for continuous renal replacement therapy. Its periodic assessment might enable physicians to deliver personalised treatments. Yet, its quantification as by extracorporeal urea clearance (Cl) is cumbersome and thus often neglected in routine practice. The aim of this in vitro study is to demonstrate the non-inferior effectiveness of assessing the current effective delivered dose using a simpler, cheaper and faster approach based on measurement of fluoride rather than urea extracorporeal Cl. METHODS: We compared urea and fluoride removal in 3 post-dilution continuous veno-venous haemofiltration (CVVH) and 3 continuous veno-venous haemodialysis (CVVHD) in vitro experimental models. Experiments ran for 180 min, using 3 L of human blood, heparin anticoagulation and a machine dose of 30 mL/kg/h. Urea and fluoride were measured in the inflow, outflow and effluent lines to compare sieving coefficients (SC), saturation coefficients (SA) and transmembrane Cls. RESULTS: In CVVH, the median SC values were 1.06 (1.02-1.07) and 1.02 (1.01-1.04) for fluoride and urea, respectively (discrepancy of 4.3%), while transmembrane convective Cls were 31.28 (30.01-31.31) mL/kg/h and 30.30 (29-31.85) mL/kg/h (discrepancy of 3.13%), respectively. In CVVHD, the median SA values were 1.01 (0.96-1.02) and 1 (0.95-1.01) for fluoride and urea, respectively (discrepancy of 1.6%), while transmembrane dialytic Cls were 30.26 (29.52-31.32) mL/kg/h and 31.16 (30-31.75) mL/kg/h (discrepancy of -2.97%), respectively. CONCLUSION: Fluoride transmembrane removal was close to that observed with urea, in terms of SC, SA and transmembrane Cl. Fluoride seems as much accurate as urea in assessing the current effective delivered dose during both CVVH and CVVHD and might therefore be adopted for dose measurement. Besides accuracy, fluoride bedside assessment could present many advantages over urea, particularly in terms of availability, costs, time requirement and rapidity of assessment.

Peripherally inserted central catheter-related thrombosis rate in modern vascular access era-when insertion technique matters: A systematic review and meta-analysis.

BACKGROUND: Technical factors at the moment of catheter insertion might have a role in peripherally inserted central catheter-related thrombotic risk. We performed a systematic review and meta-analysis to define the actual rate of peripherally inserted central catheter-related symptomatic deep vein thrombosis in patients in whom catheter insertion was performed according to ultrasound guidance, appropriate catheter size choice, and proper verification of tip location. METHODS: We searched Medline, Embase, and Cochrane Library. Only prospective observational studies published in peer-reviewed journals after 2010 up to November 2018 reporting peripherally inserted central catheter-related deep vein thrombosis rate were included. All studies were of adult patients who underwent peripherally inserted central catheter insertion. Results were restricted to those studies which included in their methods ultrasound guidance for venipuncture, catheter tip location, and a catheter size selection strategy. Random-effect meta-analyses and arcsine transformation for binomial data were performed to pool deep vein thrombosis weighted frequencies. RESULTS: Of the 1441 studies identified, 15 studies involving 5420 patients and 5914 peripherally inserted central catheters fulfilled our inclusion criteria. The weighted frequency of peripherally inserted central catheter-related deep vein thrombosis was 2.4% (95% confidence interval = 1.5-3.3) and remained low in oncologic patients (2.2%, 95% confidence interval = 0.6-3.9). Thrombotic rate was higher in onco-hematologic patients (5.9%, 95% confidence interval = 1.2-10). Considerable heterogeneity (I2 = 74.9) was observed and all studies were considered at high risk of attrition bias. CONCLUSIONS: A proper technique is crucial at the moment of peripherally inserted central catheter insertion. Peripherally inserted central catheter-related deep vein thrombosis rate appears to be low when evidence-based technical factors are taken into consideration during the insertion procedure.

Albumin Loss and Citrate Load in Pre-Dilution High Cut-Off-CVVHDF with Regional Citrate (18 mmol/L) and High Cut-Off CVVHD with Systemic Heparin: An in vitro Study.

BACKGROUND: Convective therapies with high cut-off membranes (HCO) are usually not recommended because of theoretical excessive albumin loss. The aim of this in vitro study is to demonstrate the noninferior safety of pre-dilution hemodiafiltration with HCO (HCO-CVVHDF) with isotonic citrate anticoagulation (18 mmol/L) with respect to heparin anticoagulated hemodialysis with HCO (HCO-CVVHD) in terms of albumin removal and citrate load. METHOD: -Albumin removal was compared in vitro between 3 pre--dilution-HCO-CVVHDF with citrate anticoagulation and 3 -HCO-CVVHD with heparin anticoagulation during 30-min single-pass and 180-min recirculation phases. RESULTS: Considering concentrations and flows in the extracorporeal circuit, the transmembrane albumin removal was 2.06 (1.51; 2.09) g and 2.09 (1.9; 2.8) g respectively for HCO-CVVHDF and HCO-CVVHD, during the single-pass phase; 2.8 (2.67; 4.59) g and 2.54 (2.35; 4.67) g, respectively, for HCO-CVVHDF and HCO-CVVHD during the recirculation phase. Based on the citrate saturation coefficients, a citrate metabolic load of 8.86 mmol/h has been calculated for HCO-CVVHDF. CONCLUSION: HCO-CVVHDF performed with regional anticoagulation with 18 mmol/L citrate solution does not induce higher -albumin transmembrane removal compared to HCO-CVVHD.

Recovery of muscle function after deep neuromuscular block by means of diaphragm ultrasonography and adductor of pollicis acceleromyography with comparison of neostigmine vs. sugammadex as reversal drugs: study protocol for a randomized controlled trial.

BACKGROUND: The extensive use of neuromuscular blocking agents (NMBAs) during surgical procedures still leads to potential residual paralyzing effects in the postoperative period. Indeed, neuromuscular monitoring in an intra-operative setting is strongly advocated. Acetylcholinesterase inhibitors can reverse muscle block, but their short half-life may lead to residual curarization in the ward, especially when intermediate or long-acting NMBAs have been administered. Sugammadex is the first selective reversal drug for steroidal NMBAs; it has been shown to give full and rapid recovery of muscle strength, thus minimizing the occurrence of residual curarization. Acceleromyography of the adductor pollicis is the gold standard for detecting residual curarization, but it cannot be carried out on conscious patients. Ultrasonography of diaphragm thickness may reveal residual effects of NMBAs in conscious patients. METHODS/DESIGN: This prospective, double-blind, single-center randomized controlled study will enroll patients (of American Society of Anesthesiologists physical status I-II, aged 18-80 years) who will be scheduled to undergo deep neuromuscular block with rocuronium for ear, nose, or throat surgery. The study's primary objective will be to compare the effects of neostigmine and sugammadex on postoperative residual curarization using two different tools: diaphragm ultrasonography and acceleromyography of the adductor pollicis. Patients will be extubated when the train-of-four ratio is > 0.9. Diaphragm ultrasonography will be used to evaluate the thickening fraction, which is the difference between the end expiratory thickness and the end inspiratory thickness, normalized to the end expiratory thickness. Ultrasonography will be performed before the initiation of general anesthesia, before extubation, and 10 and 30 min after discharging patients from the operating room. The secondary objective will be to compare the incidence of postoperative complications due to residual neuromuscular block between patients who receive neostigmine and those who receive sugammadex. DISCUSSION: Postoperative residual curarization is a topic of paramount importance, because its occurrence can cause complications and increase the length of stay in hospital and the related costs. Diaphragm ultrasound assessment may become a bedside integrative tool in the neuromuscular monitoring field to detect concealed residual curarization in surgical patients who have received paralyzing agents. TRIAL REGISTRATION: EudraCT, 2013-004787-62. Registered on 18 June 2014, as "Evaluation of muscle function recovery after deep neuromuscular blockade by acceleromyography of the adductor pollicis or diaphragmatic echography: comparison between sugammadex and neostigmine." ClinicalTrials.gov, NCT02698969 . Registered on 15 February 2016, as "Recovery of Muscle Function After Deep Neuromuscular Block by Means of Diaphragm Ultrasonography and Adductor Pollicis Acceleromyography: Comparison of Neostigmine vs. Sugammadex as Reversal Drugs."

Vasodilator activity of hydrogen sulfide (H2S) in human mesenteric arteries.

The role of endogenous H2S has been highlighted as a gaseous transmitter. The vascular smooth muscle inhibitory effects of H2S have been characterized in isolated aorta and mesenteric arteries in rats and mice. Our study was aimed at investigating the vascular effects of H2S on human isolated mesenteric arteries and examining the underlying mechanisms involved. All experiments were performed on rings (4-8mm long) of human mesenteric arteries obtained from patients undergoing abdominal surgery. Ethical approval was obtained from the Ethics Committee of the University Hospital of the University of Florence (app. N. 2015/0024947). The effect of NaHS, an H2S donor, was determined using noradrenaline pre-contracted human isolated mesenteric rings. NaHS evoked a concentration-dependent relaxation (EC50 57µM). In contrast, homocysteine, an endogenous precursor of H2S, failed to affect human isolated mesenteric rings. Vasorelaxant response to NaHS was reduced by endothelium removal, application of the nitric oxide synthase inhibitor L-NAME and ODQ inhibitor of cyclic GMP. SQ 22536, an adenylate-cyclase inhibitor, failed to block NaHS-induced vasorelaxation. Inhibition of endogenous prostanoid production by indomethacin significantly reduced NaHS induced vasorelaxation. The role of potassium channels was also examined: blockers of the Ca2+-dependent potassium channel, charybdotoxin and apamin, failed to have any influence on the relaxant response to NaHS on this vascular tissue. In summary, H2S induced relaxation of isolated rings of human mesenteric arteries. Endothelium-dependent related mechanisms with the stimulation of ATP-sensitive potassium channels represents important cellular mechanisms for H2S effect on human mesenteric arteries.

Effects of prolonged ischemia on human skeletal muscle microcirculation as assessed by near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) has been used to detect in vivo microvascular alterations by means of a vascular occlusion test. We sought to analyse by NIRS the microcirculatory profile of patients undergoing prolonged tourniquet-induced bloodless condition for extremity surgery, and compare the results with time of ischemia and comorbidities. We conducted a prospective observational study on 42 patients undergoing upper limb surgery. Regional anaesthesia was achieved and ischemia was induced by a tourniquet cuffed at 250 mmHg. The probe of a NIRS monitor (InSpectra 325, Hutchiston, USA) was placed on the brachial muscle, and muscle oxygen saturation (StO2) was recorded continuously before anaesthesia, during and after surgery. The following variables were recorded: baseline StO2, StO2 desaturation slope during occlusion (dSlope, units/s), resaturation rate following ischemia (RR, units/s), hyperaemic peak (peak, units), and duration of the hyperaemic period following ischemia (hyperaemic time, s). Values of dSlope were similar among all patients. RR and hyperaemic time were significantly correlated with the duration of ischemia, but not with comorbidities [p = 0.007 CI (-35.64 to -13.1), and p < 0.001 CI (0.049-0.159), respectively]. Grouping patients by duration of ischemia (30, 60, or 90 min), we found a significant decrease in RR after 60 and 90 min (p < 0.001 and p = 0.03, respectively). Hyperaemic peak was lower in the 90 min group (83.9 ± 6.8 vs. 91.2 ± 5.7 %, p = 0.02) whereas the hyperaemic time was significantly increased (595 ± 136 vs. 429 ± 107 min, p < 0.001). Alterations of skeletal muscle microcirculation were correlated with the duration of ischemia, but not with comorbidities. We observed an initial impairment of the microcirculatory recovery at 90 min of ischemia.

Changes in ceftriaxone pharmacokinetics/pharmacodynamics during the early phase of sepsis: a prospective, experimental study in the rat.

BACKGROUND: Sepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB) with consequent albuminuria. We examined whether the pharmacokinetics-pharmacodynamics (PK/PD) of ceftriaxone (CTX), an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition. METHODS: A prospective, experimental, randomized study was carried out in adult male Sprague-Dawley rats. Sepsis was induced by cecal ligation and puncture (CLP). Rats were divided into two groups: Sham-operated and CLP. CTX (100 mg i.p., equivalent to 1 g dose in humans) was administered in order to measure plasma and lung CTX concentrations at several time-points: baseline and 1, 2, 4 and 6 h after administration. CTX was measured by High Performance Liquid Chromatography (HPLC). The morphological status of the sialic components of the GFB barrier was assessed by lectin histo-chemistry. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA >90%) for 80 and 100% of Tfree > minimum inhibitory concentration (MIC) for 80 and 100% of dosing interval. MEASUREMENTS AND MAIN RESULTS: After CLP, sepsis developed in rats as documented by the growth of polymicrobial flora in the peritoneal fluid (≤1 × 101 CFU in sham rats vs 5 × 104-1 × 105 CFU in CLP rats). CTX plasma concentrations were higher in CLP than in sham rats at 2 and 4 h after administration (difference at 2 h was 47.3, p = 0.012; difference at 4 h was 24.94, p = 0.004), while lung penetration tended to be lower. An increased urinary elimination of protein-bound CTX occurred (553 ± 689 vs 149 ± 128 mg/L, p < 0.05; % of bound/total CTX 22 ± 6 in septic rats vs 11 ± 4 in sham rats, p < 0.01) and it was associated with loss of the GFB sialic components. According to Monte Carlo simulation a PTA > 90% for 100% of the dosing interval was reached neither for sham nor CLP rats using MIC = 1 mg/L, the clinical breakpoint for Enterobacteriacee. CONCLUSIONS: Sepsis causes changes in the PK of CTX and an alteration in the sialic components of the GFB, with consequent loss of protein-bound CTX. Among factors that can affect drug pharmacokinetics during the early phases of sepsis, urinary loss of both free and albumin-bound antimicrobials should be considered.

Postoperative acute kidney injury in high-risk patients undergoing major abdominal surgery.

PURPOSE: Acute kidney injury (AKI) is a frequent complication in high-risk patients undergoing major surgery and is associated with longer hospital stay, increased risk for nosocomial infection and significantly higher costs. MATERIALS AND METHODS: A prospective observational study exploring the incidence of AKI (AKIN classification at any stage) in high-risk patients within 48 hours after major abdominal surgery was conducted. Patients' preoperative characteristics, intraoperative management, and outcome were evaluated for associations with AKI using a logistic regression model. RESULTS: Data from 258 patients were analyzed. Thirty-one patients (12%) developed AKI, reaching the AKIN stage 1. No patient reached an AKIN stage higher than 1. AKI patients were older (75.2 vs 70.2 years; P = 0.0113) and had a higher body mass index (26.5 vs 25.1 kg/m(2)). In addition, AKI patients had a significantly longer ICU length of stay (3.4 vs 2.4 days; P= .0017). Creatinine levels of AKI patients increased significantly compared to the preoperative levels at 24 (P= .0486), 48 (P= .0011) and 72 hours (P= .0055), while after 72 hours it showed a downwards trend. At ICU discharge, 28 out of 31 patients (90.3%) recovered preoperative levels. Multivariate analysis identified age (OR 1.088; P= .002) and BMI (OR 1.124; P= .022) as risk factors for AKI development. Moreover, AKI development was an independent risk factor for ICU stays longer than 48 hours (OR 2.561; P= .019). CONCLUSIONS: Mild AKI is a not rare complication in high-risk patients undergoing major abdominal surgery. Although in almost the totality of cases, the indicators of renal function recovered to preoperative levels, post-operative AKI represents a primary risk factor for a prolonged ICU stay.

Hemodialysis with High Cut-Off Hemodialyzers in Patients with Multi-Drug Resistant Gram-Negative Sepsis and Acute Kidney Injury: A Retrospective, Case-Control Study.

BACKGROUND: Hemodialysis with high cut-off continuous veno-venous hemodialyzer (HCO-CVVHD) removes mediators of organ dysfunction during sepsis. This study assessed the clinical effects of HCO-CVVHD as compared to high-flux (HF) membranes during gram-negative sepsis. METHODS: Intensive care unit (ICU), septic patients treated with HCO-CVVHD or HF-CVVHDF for AKI were retrospectively observed (January 2013-December 2014). Mechanical ventilation, vasopressors' requirements, ICU length of stay (LOS) and ICU in-hospital mortality were compared between groups. RESULTS: Sixteen HCO and 8 HF patients were observed. Isolated pathogens included Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa. Median ratios of days-on-vasopressors and days-on-mechanical ventilation/ICU-LOS were 0.5, 1 and 0.8, 1 for HCO and HF groups (p < 0.03), respectively. ICU-LOS was 16 and 9 days (HCO- and HF-group, p = 0.03). ICU mortality rates were 37.5 and 87.5% for HCO and HF groups, respectively (p = 0.03). No statistical difference was found in in-hospital morality. CONCLUSION: Patients in HCO-CVVHD group spent lesser number of days on vasopressors and mechanical ventilation as a ratio to total ICU-LOS. In the same group, a reduction in ICU mortality was observed.

Urinary Strong Ion Difference as a Marker of Renal Dysfunction. A Retrospective Analysis.

INTRODUCTION: The kidneys play a crucial role in the regulation of electrolytes and acid-base homeostasis. Urinary Strong Ion Difference (SIDu = NaU + KU-ClU) represents an important aspect of renal acid-base regulation. We evaluated the role of SIDu as a marker of renal dysfunction in critically ill patients. MATERIALS AND METHODS: Patients admitted to the Medical Intensive Care Unit with a diagnosis of AKI for whom concomitant urinary samples available for SIDu calculation were retrospectively reviewed and staged according to KDIGO criteria for 3 days from inclusion. Patients were classified as Recovered (R-AKI) or Persistent-AKI (P-AKI) whether they exited KDIGO criteria within the 3-day observation period or not. A control group with normal renal function and normal serum acid-base and electrolytes was prospectively recruited in order to identify reference SIDu values. RESULTS: One-hundred-and-forty-three patients with a diagnosis of AKI were included: 77 with R-AKI, and 66 with P-AKI. Thirty-six controls were recruited. Patients with P-AKI had more severe renal dysfunction and higher mortality than patients with R-AKI (SCr 2.23(IQR:1.68-3.45) and 1.81(IQR1.5-2.5) mg/dl respectively, p<0.001; 24-h UO 1297(950) and 2100(1094) ml respectively, p = 0.003); 30-d mortality, 39% and 13% respectively; p<0.001). SIDu significantly differed between groups, with rising values from controls to P-AKI groups (16.4(12), 30(24) and 47.3(21.5) mEq/l respectively, p<0.001). DISCUSSION: SIDu may be a simple and inexpensive tool in AKI patients' evaluation. Further research is needed to evaluate the ability of SIDu to identify patients with renal dysfunction before derangements in serum creatinine or urine output are observed.

The experience of setting up a resident-managed Acute Pain Service: a descriptive study.

BACKGROUND: The benefits of an Acute Pain Service (APS) for pain management have been widely reported, but its diffusion is still limited. There are two APS models: anesthesiologist-based and a nurse-based model. Here we describe the development of a different APS model managed by anesthesia residents, and we report the first year of activity in a tertiary Italian university hospital (Careggi University Hospital, Florence, IT). METHODS: Patients were included in the APS were those undergoing abdominal and urologic surgery causing moderate or severe postsurgical pain. The service was provided for patients, beginning upon their exit from the operating room, for 4, 12, 24 and 48 h for iv, and up to 72 h for epidural therapy. Vital signs, static/dynamic VAS, presence of nausea/vomiting, sedation level, and Bromage scale in case of epidural catheter, were monitored. RESULTS: From September 2013 to April 2015, a total of 1054 patients who underwent major surgery were included in the APS: 542 from abdominal surgery and 512 from urological surgery. PCA and epidural analgesia were more adopted in general surgical patients than in urology (48% vs 36% and 15% vs 2%, respectively; P < 0.0001). Patients who underwent to abdominal surgery had a significantly higher self-administration of morphine (30.3 vs 22.7 mg; P = 0.0315). Elastomeric pump was the analgesic of choice in half of the urologic patients compared to a quarter of the general surgical patients (P < .0001). Among the different surgical techniques, epidural analgesia was used more in open (16.5%) than in videolaparoscopic (1.9%) and robotic technique (1.1%), whereas PCA was predominant in videolaparoscopic (46.5%) and robotic technique (55.5%) than in open technique (31.4%). CONCLUSIONS: The creation of APS, managed by anesthesia residents, may represent an alternative between specialist-based and nurse-based models.

Linezolid extracorporeal removal during haemodialysis with high cut-off membrane in critically ill patients.

Continuous venovenous haemodialysis with high cut-off membrane (HCO-CVVHD) is often used in critically ill septic patients with acute kidney injury (AKI) to sustain renal function and to remove circulating inflammatory mediators. The aim of this study was to analyse the extracorporeal removal of linezolid and related alterations in pharmacokinetic/pharmacodynamic (PK/PD) parameters during HCO-CVVHD. Three critically ill septic patients with AKI, treated with linezolid and HCO-CVVHD, were prospectively observed. To calculate the extracorporeal clearance of linezolid and the PK parameters, effluent, pre-filter and post-filter samples were contemporaneously collected before linezolid infusion, just after 1-h infusion (maximum serum concentration; C(max)), at 3 h and 6 h after dosing, and before the next dose (trough serum concentration; C(min)). Linezolid C(max) and C(min) (pre-filter) ranged from 10.4-23.5 mg/L and from 2.9-10.3 mg/L. The dialysate saturation coefficient was 0.66-0.85 and the extracorporeal clearance with a diffusive dose of 35 m L/kg/h ranged from 2.1-2.5 L/h. Total linezolid clearance was between 1.7 L/h and 6.3 L/h. The total area under the plasma concentration-time curve (AUC0-∞) ranged from 95.1 mgh/L to 352.9 mgh/L, in accordance with the different clinical conditions. AUCfree/MIC ratios were always <85 for an MIC of 4.0 mg/L, and two of three patients did not reach the optimal PK/PD target of ≥85 even when using an MIC of 2.0 mg/L. Although extracorporeal clearance may affect linezolid total clearance, the clinical features of critically ill septic patients appear to be mainly responsible for the high variability of linezolid serum concentrations.

Fractures of totally implantable central venous ports: more than fortuity. A three-year single center experience.

PURPOSE: Totally implantable venous access devices (Ports) represent the mainstay for infusion therapy in patients undergoing chemotherapy, total parenteral nutrition and/or long-term antibiotic treatment. Amongst mechanical complications, lesions of the catheter wall represent a rare but potentially severe condition. We report our experience with the accidental detection of catheter ruptures in a series of ports removed for complication or for end of use. METHODS: All ports removed from January 2011 to June 2013 were considered. All removed ports had been inserted according to a standardized protocol including ultrasound-guided percutaneous venipuncture (out-of-plane or in-plane approaches) and electrocardiogram-guided positioning of the tip. Once removed, each catheter was checked by inspection and saline instillation in order to evaluate the integrity of the device itself and rule out possible ruptures. RESULTS: In over 338 removed ports, 12 Groshong catheters out of 65 (18.5%) had evidence of partial rupture of the catheter wall. Amongst considered variables, "out-of-plane" approach and type of port (silicon, closed tip with Groshong valve) were the only ones significantly associated with catheter ruptures (p=0.0003 and 0.0008, respectively). We could detect no evidence of rupture in any silicon open-ended catheter (Celsite ports) or in any catheter inserted by "in-plane" approach to the vein. CONCLUSIONS: The actual advantage of using port connected with Groshong silicon catheters should be questioned, since apparently they are more fragile than standard catheters. Furthermore, ultrasound-guided "out-of-plane" puncture of the internal jugular vein should be discouraged.

Minocycline but not tigecycline is neuroprotective and reduces the neuroinflammatory response induced by the superimposition of sepsis upon traumatic brain injury.

OBJECTIVE: The development of sepsis in patients with traumatic brain injury increases mortality, exacerbates morphological and functional cerebral damage, and causes persistent neuroinflammation, including microglial activation. The administration of antibiotics possessing both antimicrobial and immunomodulatory activity might attenuate both sepsis and posttraumatic cerebral inflammation. We compared the potential therapeutic efficacy of two tetracyclines, minocycline and the newer generation tigecycline, on functional neurobehavioral impairment and regional histopathological damage in an experimental model of combined traumatic brain injury and sepsis. DESIGN: Prospective, experimental animal study. SETTING: University Research Laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Controlled cortical impact was used to induce traumatic brain injury and cecal ligation and puncture for sepsis. Immediately following injury, animals were treated with minocycline (45 mg/kg intraperitoneal), tigecycline (7.5 mg/kg intraperitoneal), or saline every 12 hours for 3 days. MEASUREMENTS AND MAIN RESULTS: The development of sepsis and cerebral inflammatory response were evaluated, respectively, by 1) growth of peritoneal microorganisms and clinical variables and 2) tumor necrosis factor-α expression in the perilesional cortex. To assess posttraumatic outcome, vestibulomotor and cognitive function were evaluated at different time points for 14 days post injury whereupon animals were killed and cerebral tissue analyzed for lesion volume, regional hippocampal (CA1/CA3) cell death, and microglial activation in the perilesional cortex, lesion core zone, and choroid plexus. Treatment with both antibiotics reduced microorganism growth, body weight loss, and mortality but had no effect on vestibulomotor or cognitive function. Minocycline alone attenuated postinjury cortical lesion volume, hippocampal CA3 neuronal cell loss, tumor necrosis factor-α expression, and the extent of microglial activation and infiltration. CONCLUSIONS: The significantly heightened mortality caused by the superimposition of sepsis upon traumatic brain injury can be reduced by administration of both antibiotics but only minocycline can decrease the extent of cell death in selectively cortical and hippocampal brain regions, via, in part, a reduction in cerebral inflammation.

High-intensity focused ultrasound provides palliation for liver metastasis causing gastric outlet obstruction: case report.

BACKGROUND: Surgery is the standard of care in several oncologic diseases. However, when non-surgical candidates are not suitable for radical treatment, palliation must be achieved at least. High-intensity focused ultrasound uses ultrasound power that can be sharply focused for highly localised application, as it is a completely non-invasive procedure. Its non-invasiveness appears to be of paramount importance in critically ill patients. CASE DESCRIPTION: We describe the use of ultrasound-guided high-intensity focused ultrasound for a large liver metastasis from breast cancer causing gastric outlet obstruction in a metastatic disease. The left liver deposit did not allow the stomach to empty due to its large volume, and the patient was unable to eat properly. The tumour was metastatic, resistant to chemotherapy and had a size that contraindicated an ablation percutaneous technique. To improve the patient's quality of life, ultrasound-guided high-intensity focused ultrasound ablation seemed the only and most suitable option. Therefore, a high-intensity focused ultrasound treatment was performed, no complications occurred and the patient's general condition has improved since the early post-procedural period. Three months after treatment, two body mass index points were gained, and the lesion decreased by 72% in volume as detected through multi-detector computed tomography follow-up. DISCUSSION AND CONCLUSION: Quality of life is an unquestionable goal to achieve, and palliation must be achieved while causing as little harm as possible. In this view, debulking surgery and percutaneous ablation technique seemed not appropriate for our patient. Instead, high-intensity focused ultrasound combined several advantages, no lesion size limit and a totally non-invasive treatment. Thus, this technique proved to be a clinically successful procedure, offering better disease control and quality of life. In circumstances where other alternatives clearly seem to fail or are contraindicated, high-intensity focused ultrasound can be used and can provide benefits. We recommend its use and development in several oncologic diseases, not only for therapeutic purposes but also for the improvement of patient's quality of life.