Identification of the zebrafish homologues of IMPG2, a retinal proteoglycan.

Photoreceptor outer segments are surrounded by a carbohydrate-rich matrix, the interphotoreceptor matrix, necessary for physiological retinal function. Few roles for molecules characterizing the interphotoreceptor matrix have been clearly defined. Recent studies have found the presence of nonsense mutations in the interphotoreceptor matrix proteoglycan 2 (IMPG2) gene in patients affected by retinal dystrophies. IMPG2 encodes for a proteoglycan synthesized by photoreceptors and secreted in the interphotoreceptor matrix. Little is known about the structure and function of this protein, we thus decided to characterize zebrafish impg2. In zebrafish there are two Impg2 proteins, Impg2a and Impg2b. We generated a phylogenetic tree based on IMPG2 protein sequence similarity among vertebrates, showing a significant similarity between humans and teleosts. The human and zebrafish proteins share conserved domains, as also shown by homology models. Expression analyses of impg2a and impg2b show a continued expression in the photoreceptor layer starting from developmental stages and continuing through adulthood. Between 1 and 6 months post-fertilization, there is a significant shift of Impg2 expression toward the outer segment region, suggesting an increase in secretion. This raises intriguing hypotheses about its possible role(s) during retinal maturation, laying the groundwork for the generation of most needed models for the study of IMPG2-related inherited retinal dystrophies.

Quantum Phase Transitions for an Integrable Quantum Rabi-like Model with Two Interacting Qubits.

A two-interacting-qubit quantum Rabi-like model with vanishing transverse fields on the qubit pair is studied. Independently of the coupling regime, this model can be exactly and unitarily reduced to two independent single-spin quantum Rabi models, where the spin-spin coupling plays the role of the transverse field. This transformation and the analytical treatment of the single-spin quantum Rabi model provide the key to prove the integrability of our model. The existence of different first-order quantum phase transitions, characterized by discontinuous two-spin magnetization, mean photon number, and concurrence, is brought to light.

68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine well-differentiated tumours.

PURPOSE: To explore the role of fully hybrid 68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine tumours (PanNETs) undergoing surgery. METHODS: One hundred eighty-seven consecutive 68Ga-DOTATOC PET/MRI scans (March 2018-June 2020) performed for gastroenteropancreatic neuroendocrine tumour were retrospectively evaluated; 16/187 patients met the eligibility criteria (68Ga-DOTATOC PET/MRI for preoperative staging of PanNET and availability of histological data). PET/MR scans were qualitatively and quantitatively interpreted, and the following imaging parameters were derived: PET-derived SUVmax, SUVmean, somatostatin receptor density (SRD), total lesion somatostatin receptor density (TLSRD), and MRI-derived apparent diffusion coefficient (ADC), arterial and late enhancement, necrosis, cystic degeneration, and maximum diameter. Additionally, first-, second-, and higher-order radiomic parameters were extracted from both PET and MRI scans. Correlations with several PanNETs' histopathological prognostic factors were evaluated using Spearman's coefficient, while the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate parameters' predictive performance. RESULTS: Primary tumour was detected in all 16 patients (15/16 by 68Ga-DOTATOC PET and 16/16 by MRI). SUVmax and SUVmean resulted good predictors of lymphnodal (LN) involvement (AUC of 0.850 and 0.783, respectively). Second-order radiomic parameters GrayLevelVariance and HighGrayLevelZoneEmphasis extracted from T2 MRI demonstrated significant correlations with LN involvement (adjusted p = 0.009), also showing good predictive performance (AUC = 0.992). CONCLUSION: This study demonstrates the role of the fully hybrid PET/MRI tool for the synergic function of imaging parameters extracted by the two modalities and highlights the potentiality of imaging and radiomic parameters in assessing histopathological features of PanNET aggressiveness.

Aerobic exercise and Orexin A: role of sympathetic activity and redox system.

Aerobic exercise is associated with the sympathetic activation evoking adaptive responses to sustain muscle engagement. Physical exercise can cause alterations in the cardiovascular activity and cellular stress may occur which could be marked by either heart rate (HR), or galvanic skin response (GSR). Moderate plasma levels of reactive oxygen species (ROS) are considered as health markers, absolving to important roles such as adaptive cellular responses to exercise. Orexin A, a hypothalamic peptide, causes a widespread stimulation of the sympathetic nervous system, playing a role in many physiological functions.

Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group.

BACKGROUND: To report on long-term results of a phase 3 trial comparing three versus five cycles of adjuvant chemotherapy (CT) with full-dose epirubicin+ifosfamide in high-risk soft tissue sarcomas (STS). METHODS: Patients (pts) were randomized to receive three preoperative cycles of epirubicin 120 mg/m2 and ifosfamide 9 g/m2 (Arm A) or to receive the same three preoperative cycles plus two postoperative cycles (Arm B). Radiotherapy could be either delivered in the preoperative or in the postoperative setting. Non-inferiority of the primary end point, OS, was assessed by the confidence interval of the hazard ratio (HR; Arm A/Arm B) derived from Cox model. RESULTS: Between January 2002 and April 2007, 164 pts were assigned to arm A and 164 to arm B. At a median follow-up (FU) of 117 months (IQ range 103-135 months), 123 deaths were recorded: 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients: 64% in Arm A and 59% in Arm B. The intention-to-treat analysis confirmed that three cycles were not inferior to five cycles (one-sided 95% upper confidence limit was 1.24). A per protocol analysis was consistent with these results. Pts with leiomyosarcoma and undifferentiated pleomorphic sarcoma (UPS) had the lowest, and the highest response rates, respectively. Consistently, Leiomyosarcoma and UPS had the worse and the best prognosis, respectively. CONCLUSIONS: At a longer FU, the non-inferiority of three cycles of a full-dose conventional CT in comparison to five is confirmed. Response to therapy is also confirmed to be associated with better survival. This regimen is currently tested within an ongoing international trial against three cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176).

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

OBJECTIVE: To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twenty-nine centres in Switzerland and Argentina. POPULATION: A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. METHODS: Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. MAIN OUTCOME MEASURES: Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. RESULTS: Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. CONCLUSION: There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour.

Identification of human tear fluid biomarkers in vernal keratoconjunctivitis using iTRAQ quantitative proteomics.

BACKGROUND: Understanding and treating vernal keratoconjunctivitis (VKC) has been a challenge because the pathogenesis is unclear and antiallergic therapy often unsuccessful. The aim of the study was to analyze peptide profiles in human tears using mass spectrometry to elucidate compositional differences between healthy subjects and patients affected by VKC. METHODS: Tears were collected from healthy subjects and VKC patients. Digested samples were treated with iTRAQ (isobaric tag for relative and absolute quantitation). Separation of tryptic peptides was realized using a MicroHPLC interfaced with a microfraction collector. MS and MS/MS mass spectra were performed using a MALDI TOF/TOF 4800 Applied Biosystem spectrometer. Protein Pilot™ software with Paragon™ algorithm v4.1.46 or GPS™ with Mascot engine was used as search engines with SwissProt or IPI human as the databases. RESULTS: A significant number of peptides were examined, and 78 proteins were successfully identified. In all VKC samples, levels of serum albumin, transferrin, and hemopexin were found up to 100 times higher than control tear levels and correlated to the severity of disease. Hemopexin, transferrin, mammaglobin B, and secretoglobin 1D were found significantly over-expressed in VKC samples compared with the control samples. Tear samples from patients treated with topical cyclosporine or corticosteroids showed a dramatic reduction in these protein levels. CONCLUSIONS: LC MALDI MS and isobaric tag for relative and absolute quantitation technique may be useful in the quantitative and qualitative characterization of the peptidoma of human tears. These techniques may identify target proteins to be used in the diagnosis and management of VKC and other inflammatory ocular surface conditions.

Interaction effects of cell diffusion, cell density and public goods properties on the evolution of cooperation in digital microbes.

Microbial cooperation typically consists in the sharing of secreted metabolites (referred to as public goods) within the community. Although public goods generally promote population growth, they are also vulnerable to exploitation by cheating mutants, which no longer contribute, but still benefit from the public goods produced by others. Although previous studies have identified a number of key factors that prevent the spreading of cheaters, little is known about how these factors interact and jointly shape the evolution of microbial cooperation. Here, we address this issue by investigating the interaction effects of cell diffusion, cell density, public good diffusion and durability (factors known to individually influence costs and benefits of public goods production) on selection for cooperation. To be able to quantify these effects across a wide parameter space, we developed an individual-based simulation platform, consisting of digital cooperator and cheater bacteria inhabiting a finite two-dimensional continuous toroidal surface. Our simulations, which closely mimic microbial microcolony growth, revealed that: (i) either reduced cell diffusion (which keeps cooperators together) or reduced public good diffusion (which keeps the public goods closer to the producer) is not only essential but also sufficient for cooperation to be promoted; (ii) the sign of selection for or against cooperation can change as a function of cell density and in interaction with diffusion parameters; and (iii) increased public goods durability has opposing effects on the evolution of cooperation depending on the level of cell and public good diffusion. Our work highlights that interactions between key parameters of public goods cooperation give rise to complex fitness landscapes, a finding that calls for multifactorial approaches when studying microbial cooperation in natural systems.

Investigation on physical restraint use in hospital: health responsibility, ethical and medical legal considerations.

Background: The issue of restraint has long been considered a difficult political and social situation, affecting both healthcare wor-kers and facilities. The practice of restraint is still widespread in many public and private care settings, but there is a lack of systemic studies capable of monitoring the phenomenon. The framing of the question essentially concerns the right to personal freedom, guaranteed by the Italian Constitution. Materials and Methods: An anonymous questionnaire was developed containing questions on knowledge of the regulations on restraints, how, ways, and when they are implemented, and general information such as age, gender, educational qualification, qualification, O.Us. to which they belong. The collected data were statistically processed (Chi-square test) with the Epi Info 7.1.5 program (CDC-Atlanta- USA). A total of 1002 questionnaires were completed. The stratification of the sample by structure shows that 73.9% were public facilities. The indicative figure is represented by the 23.8% of respondents who say that "the restraint is not noted in the medical record". Conclusions: Restraint could be a real risk for the healthcare worker, encroaching on the issue of health liability. It is therefore important to raise awareness among healthcare professionals and top management of the need to structure, at company level, procedures that comply with the "Recommendations on physical restraint" to overcome the use of restraint through the improvement of care pathways in compliance with organizational and risk management standards.

Phase II study on lapatinib in advanced EGFR-positive chordoma.

BACKGROUND: To report on a prospective, investigator-driven, phase II study on lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma patients. PATIENTS AND METHODS: From December 2009 to January 2012, 18 advanced progressing chordoma patients entered this study (median age: 61 years; disease extent: metastatic 72% and locally advanced 28%). Epidermal growth factor receptor (EGFR) expression and activation were evaluated by immunohistochemistry and/or phospho-arrays, real-time polimerase chain reaction, fluorescence immunostaining. Fluorescence in situ hybridization analysis was also carried out. Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day), until progression or toxicity. The primary study end point was response rate (RR) as per Choi criteria. Secondary end points were RR by Response Evaluation Criteria in Solid Tumor (RECIST), overall survival, progression-free survival (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response (PR) + stable disease (SD) ≥ 6 months). RESULTS: All patients were evaluable for response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6 [interquartile (IQ) range 3-8] months. Median PFS by RECIST was 8 (IQ range 4-12) months, with a 22% CBR. CONCLUSIONS: This phase II study showed a modest antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR targeting in chordoma needs to be further investigated, both clinically and preclinically. Clinical trial Registration No: EU Clinical Trials Register trial no. 2009-014456-29.

The epidemiology of life-threatening complications associated with reproductive process in public hospitals in Argentina.

OBJECTIVE: To analyse life-threatening obstetric complications that occurred in public hospitals in Argentina. DESIGN: Multicentre collaborative cross-sectional study. SETTING: Twenty-five hospitals included in the Perinatal Network of Buenos Aires Metropolitan Area. POPULATION: Women giving birth in participating hospitals during a 1-year period. METHODS: All cases of severe maternal morbidity (SMM) and maternal mortality (MM) during pregnancy (including miscarriage and induced abortion), labour and puerperium were included. Data were collected prospectively. MAIN OUTCOME MEASURES: Identification criteria, main causes and incidence of SMM; case-fatality rates, morbidity-mortality index and effective intervention's use rate. RESULTS: A total of 552 women with life-threatening conditions were identified: 518 with SMM, 34 with MM. Identification criteria for SMM were case-management (48.9%), organ dysfunction (15.2%) and mixed criteria (35.9%). Incidence of SMM was 0.8% (95% confidence interval [95% CI] 0.73-0.87%) and hospital maternal death ratio was 52.3 per 100 000 live births (95% CI 35.5-69.1). Main causes of MM were abortion complications and puerperal sepsis; main causes of SMM were postpartum haemorrhage and hypertension. Overall case-fatality rate was 6.2% (95% CI 4.4-8.6): the highest due to sepsis (14.8%) and abortion complications (13.3%). Morbidity-mortality index was 15:1 (95% CI 7.5-30.8). Use rate of known effective interventions to prevent or treat main causes of MM and SMM was 52.3% (95% CI 46.9-57.7). CONCLUSIONS: This study describes the importance of life-threatening obstetric complications that took place in public hospitals with comprehensive obstetric care and the low utilisation of known effective interventions that may decrease rates of SMM and MM. It also provides arguments that justify the need to develop a surveillance system for SMM.

Plasma heavy metal levels correlate with deregulated gene expression of detoxifying enzymes in osteoporotic patients.

Heavy metal levels appear to be associated with low bone mineral density (BMD) and the consequent osteoporosis risk, but the relationship with the disease has not been clearly defined. The altered expression pattern of numerous genes, including detoxifying genes, seems to play a pivotal role in this context, leading to increased susceptibility to several diseases, including osteoporosis. The purpose of this study is to analyse circulating heavy metals levels and the expression of detoxifying genes in osteoporotic patients (OPs, n = 31), compared with healthy subjects (CTRs, n = 32). Heavy metals concentration in plasma samples was determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), and the subsequent expression analysis of NAD(P)H quinone dehydrogenase 1 (NQO1), Catalase (CAT), and Metallothionein 1E (MT1E) genes in Peripheral Blood Mononuclear Cells (PBMCs) was assessed by real-time polymerase chain reaction (qRT-PCR). Copper (Cu), mercury (Hg), molybdenum (Mo) and lead (Pb) were found to be significantly higher in the plasma of OPs compared to CTRs. Analysis of the expression levels of detoxifying genes showed a significant decrease in CAT and MT1E in OP group. In addition, Cu correlated positively with the expression levels of both CAT and MT1E in CTRs group and MT1E in OPs. This study shows an increased circulating concentration of certain metals combined with an altered expression pattern of detoxifying genes in OPs, highlighting a novel aspect to be investigated in order to better characterize the role of metals in the pathogenesis of osteoporosis.

Sunitinib malate in solitary fibrous tumor (SFT).

BACKGROUND: To report on sunitinib activity in a retrospective series of 35 solitary fibrous tumor (SFT) treated at a single institution. PATIENTS AND METHODS: From April 2008, 35 patients with progressive advanced SFT (male/female: 20/15; mean age: 58 years; meningeal/extrameningeal: 6/29; locally advanced/metastatic: 15/20; prior chemotherapy: 25) were treated, on an individual use basis, with continuous-dosing sunitinib 37.5 mg/day. Platelet-derived growth factor receptor beta (PDGFRB) and vascular endothelial growth factor receptor 2 (VEGFR2) status were assessed by immunohistochemistry and, in a subgroup of patients, by real time PCR. RESULTS: Thirty-one patients were assessable for response by RECIST (one early death; three early interruptions). Best responses were 2 partial response (PR), 16 stable disease, 13 progressive disease. A <30% decrease in size was observed in three patients. Fourteen of 29 patients assessable by Choi criteria had a PR. Median progression-free survival by RECIST was 6 months (range 1-22). In two of six patients, resistance to sunitinib was overcome by increasing sunitinib to 50 mg/day. PDGFRB and/or VEGFR2 were positive in all cases and not predictive of response; a less aggressive morphology corresponded to an increased response rate (53% PR by Choi in the malignant SFT, 20% PR in the pleomorphic/dedifferentiated SFT). CONCLUSIONS: Sunitinib is active in SFT. Response can be long-lasting.

Ten answers to key questions for fluid management in intensive care.

This review focuses on fluid management of critically ill patients. The topic is addressed based on 10 single questions with simplified answers that provide clinicians with the basic information needed at the point of care in treating patients in the Intensive Care Unit. The review has didactic purposes and may serve both as an update on fluid management and as an introduction to the subject for novices in critical care. There is an urgent need to increase awareness regarding the potential risks associated with fluid overload. Clinicians should be mindful not only of the indications for administering fluid loads and of the type of fluids administered, but also of the importance to set safety limits. Lastly, it is important to implement proactive strategies seeking to establish negative fluid balance as soon as the clinical conditions are considered to be stable and the risk of deterioration is low.

Molecular cloning and enzymatic characterization of sheep CYP2J.

Cytochrome P450 (CYP) 2Js have been studied in various mammals, but not in sheep, as an animal model used to test veterinary drug metabolism. Sheep CYP2J was cloned from liver messenger RNA (mRNA) by RACE. The cDNA, after modification at its N- and C-terminals, was expressed in Escherichia coli and the sheep CYP2J protein, purified by chromatography, was 80% homologous to human and monkey CYP2J2. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments showed that CYP2J mRNA was expressed in liver, cortex, respiratory and olfactory mucosa, heart, bronchi, lung, spleen, small intestine and kidney. The purified enzyme was catalytically active towards aminopyrine, all-trans-retinoic acid, and particularly arachidonic acid forming 20-HETE, 19-HETE, and 18-HETE (about 86% of the total) and 14,15-, 11,12-, 8,9-, and 5,6-EETs (cis-epoxyeicosatrienoic acids; about 14% of total), with a regioselectivity similar to that shown by the mammalian CYP2J2s.

Post-operative analgesia following total knee arthroplasty: comparison of low-dose intrathecal morphine and single-shot ultrasound-guided femoral nerve block: a randomized, single blinded, controlled study.

BACKGROUND AND OBJECTIVES: Total knee arthroplasty often results in marked postoperative pain. A recent meta-analysis supports the use of femoral nerve block or alternatively spinal injection of morphine plus local anaesthetic for post-operative analgesia. On the other hand, the use of intrathecal morphine may be associated with a large number of distressing side effects (itching, urinary retention, nausea and vomiting, delayed respiratory depression). The aim of this study was to compare the effectiveness of femoral nerve block and low dose intrathecal morphine in post-operative analgesia after primary unilateral total knee arthroplasty. MATERIAL AND METHODS: Fifty-two consecutive patients scheduled for primary unilateral total knee arthroplasty were allocated to the intrathecal morphine group (ITM group) or to the femoral nerve block group (FNB group). In ITM group a subarachnoid puncture was performed at the L3-L4 inter-vertebral space with hyperbaric bupivacaine 15 mg plus 100 mcg of preservative-free morphine. Patients allocated to the FNB group received a single-injection ultrasound-assisted femoral nerve block with ropivacaine 0.75% 25 ml before the spinal injection of hyperbaric bupivacaine 15 mg. All patients received postoperative patient-controlled-analgesia (PCA) morphine, using a 1-mg bolus and a 5-minute lockout period. Data were analyzed using Student t test or two-way analysis of variance (ANOVA) for repeated measures with time and treatment as the 2 factors. Post hoc comparisons were performed by Bonferroni test. Statistical significance for all test was a p value < 0.05. RESULTS: Patient characteristics were similar between the 2 groups. We found a statistically significant differences in postoperative pain between the two groups: ITM group had the lower visual analogic pain score (VAS) values. Morphine consumption was lower in the ITM group: average consumption within the first 6 hours was 0.9 mg in IT group compared to 3.1 mg in FNB group; at 12 h 4.2 mg vs 6.3 mg; at 24 h 6.9 mg vs 10.3 mg; at 48 h 9.7 mg vs 13.6 mg. However, the difference in the opiate consumption was not statistically different (p value = 0.06). Thirteen patients in ITM group experienced itching, only 5 in FNB group. We did not find any difference in the two treatment groups in the use of antiemetic and antipruritic medication. No cases of respiratory depression was recorded. CONCLUSIONS: Our results show that low dose of intrathecal morphine may be safe and more efficient than single-shot femoral nerve block for post-operative analgesia after total knee arthroplasty.

Protection of ovarian tissue from radiotherapy.

Advances researches in the diagnosis and treatment of childhood, adolescent and adult cancer have greatly increased the life expectancy of premenopausal women with cancer. However, one of the serious side effects of these treatments is the risk of damage to fertility. The ovaries are very sensitive to cytotoxic and radiotherapeutic treatment. The only established method of fertility preservation is embryo cryopreservation according to the Ethics Committee of the American Society for Reproductive Medicine (2005), but this option requires the patient to be of pubertal age, have a partner or use donor sperm, and be able to undergo a cycle of ovarian stimulation, which is not possible when the radiotherapy has to be initiated immediately or when stimulation is contraindicated according to the type of cancer. For patients who need immediate radiotherapy, cryopreservation of ovarian tissue is the only possible alternative. This manuscript reports the different techniques of cryopreservation and the results of transplantation of cryopreserved ovarian tissue. The current techniques allow cryopreservation of human ovarian fragments for a long time with good follicular survival rate after thawing. Numerous studies ultimately in this field have demonstrated to improve the survival rate of the oocytes and cryopreserved follicles. Moreover this manuscript includes a case of a 17-year-old girl who had to undergo pelvic irradiation for non-Hodgkin's lymphoma and the laparoscopic treatment to preserve the fertility (Fig. 2, Ref. 47).

Ten answers to key questions for fluid management in intensive care.

This review focuses on fluid management of critically ill patients. The topic is addressed based on 10 single questions with simplified answers that provide clinicians with the basic information needed at the point of care in treating patients in the Intensive Care Unit. The review has didactic purposes and may serve both as an update on fluid management and as an introduction to the subject for novices in critical care. There is an urgent need to increase awareness regarding the potential risks associated with fluid overload. Clinicians should be mindful not only of the indications for administering fluid loads and of the type of fluids administered, but also of the importance to set safety limits. Lastly, it is important to implement proactive strategies seeking to establish negative fluid balance as soon as the clinical conditions are considered to be stable and the risk of deterioration is low.