Drop-on-Demand Pyro-Electrohydrodynamic Printing of Nematic Liquid Crystal Microlenses.

Inkjet printing of liquid crystal (LC) microlens arrays is particularly appealing for the development of switchable 2D/3D organic light-emitting diode (OLED) displays, as the printing process ensures that the lenses can be deposited directly and on-demand onto the pixelated OLED layer without the need for additional steps, thus simplifying fabrication complexity. Even if different fabrication technologies have been employed and good results in LC direct printing have already been achieved, all the systems used require costly equipment and heated nozzles to reduce the LC solution's viscosity. Here, we present the direct printing of a nematic LC (NLC) lens by a Drop-on-Demand (DoD) inkjet printing by a pyro-electrohydrodynamic effect for the first time. The method works at ambient temperature and avoids dispensing nozzles, thus offering a noncontact manipulation approach of liquid with high resolution and good repeatability on different kinds of substrates. NLC microlenses are printed on different substrates and fully characterized. Polarization properties are evaluated for various samples, i.e., NLC lenses on unaligned and indium-tin oxide (ITO) aligned. Moreover, an in-depth characterization of the NLC lenses is reported by polarized optical microscopy and by analyzing the birefringence in digital holographic microscopy.

Highly sensitive detection of the neurodegenerative biomarker Tau by using the concentration effect of the pyro-electrohydrodynamic jetting.

It is largely documented that neurodegenerative diseases can be effectively treated only if early diagnosed. In this context, the structural changes of some biomolecules such as Tau, seem to play a key role in neurodegeneration mechanism becoming eligible targets for an early diagnosis. Post-translational modifications are responsible to drive the Tau protein towards a transition phase from a native disorder conformation into a preaggregation state, which then straight recruits the final fibrillization process. Here, we show for the first time the detection of pre-aggregated Tau in artificial urine at femto-molar level, through the concentration effect of the pyro-electrohydrodynamic jet (p-jet) technique. An excellent linear calibration curve is demonstrated at the femto-molar level with a limit of detection (LOD) of 130 fM. Moreover, for the first time we show here the structure stability of the protein after p-jet application through a deep spectroscopic investigation. Thanks to the small volumes required and the relatively compact and cost-effective characteristics, this technique represents an innovative breakthrough in monitoring the early stage associated to neurodegeneration syndromes in different scenarios of point of care (POC) and such as for example in long-term human space exploration missions.

Primary malignant phyllodes tumors of the breast: A retrospective analysis from a referral center.

BACKGROUND: The treatment for primary malignant phyllodes tumors of the breast (B-MPT) consists of wide local excision with negative margins (≥1 cm). However, because of their rarity, prognostic factors, type of surgery and adjuvant treatments are still a matter of debate. METHODS: We conducted a single-center retrospective study to describe outcomes and prognostic factors of patients with primary B-MPT, who underwent breast surgery from January 2000 to December 2021. The primary endpoint was the cumulative incidence of any recurrence. Secondary endpoints were the cumulative incidences of distant and local recurrences. RESULTS: 131 patients were included, of whom all received surgery, 5 adjuvant anthracycline-based chemotherapy and 15 radiation therapy. After a median follow-up of 6.4 years, the cumulative incidences at 5-years of any, local and distant recurrences were of 26% (95% Confidence Interval [CI], 4-34%), 16% (95%CI, 10-24%) and 10% (95%CI, 5.3-16%), respectively. Tumor size ≥ 5 cm was associated with higher distant recurrences (p = 0.05); instead, among small tumors (<5 cm), distant recurrences were higher in those with heterologous differentiation and/or multifocal disease (p = 0.06). Type of breast surgery (mastectomy vs. lumpectomy/excision) was not found to be significantly associated with distant (p = 0.32) or local (p = 0.17) recurrence, even after controlling local recurrence incidence for negative pathologic prognostic factors (p = 0.17). CONCLUSIONS: The natural history of B-MPT is burdened by local and distant recurrences. Pathologic prognostic factors (i.e., tumor size, heterologous differentiation and multifocal disease) more than the type of wide breast surgery (mastectomy vs. lumpectomy) seem to represent the most significant prognostic factor for recurrences.

Oscillation Dynamics of Dielectric Polymer Droplets during Electrohydrodynamic Jetting in a Wide Range of Viscosities.

The electrohydrodynamic (EHD) jetting of fluids is used for several applications such as inkjet printing, atomization of analyte in mass spectrometry, liquid metal alloy ion sources, and electrospinning of polymer fibers. Historically, the bulk of research has focused on nonviscous, highly conductive fluids which are most suitable for EHD spray and printing, while there is relatively little experimental work on EHD jetting of highly viscous liquid dielectrics. We studied the dynamics of oscillation and pulsating jetting from a suspended drop of polydimethylsiloxane (PDMS) polymers in an electric field, with particular attention to the viscosity dependence of the oscillation period and meniscus elongation and contraction time over a wide viscosity range (102-105 cSt). The reported results could help the appropriate design of EHD processes and may open new possibilities for the rheological characterization of liquid polymers using small volumes at the scale of nanoliters.

Genetic Alterations of Melanoma Brain Metastases: A Systematic Review and Meta-Analysis.

BACKGROUND: Data on molecular alterations harbored by melanoma brain metastases (MBMs) are limited, and this has hampered the development of more effective therapeutic strategies. We conducted a systematic review and meta-analysis of all the studies reporting DNA sequencing data of MBMs, in order to identify recurrently mutated genes and molecular pathways significantly enriched for genetic alterations. METHODS: We searched PubMed, Embase and Scopus for articles published from the inception of each database to June 30, 2021. We included in the analysis all the studies that reported individual patient data on DNA sequencing of MBMs, assessing single nucleotide variants (SNVs) and/or gene copy number variations (CNVs) in at least five tumor samples. Meta-analysis was performed for genes evaluated for SNVs and/or CNVs in at least two studies. Pooled proportions of samples with SNVs and/or CNVs was calculated by applying random-effect models based on the DerSimonian-Laird method. Gene-set enrichment analysis (GSEA) was performed to identify molecular pathways significantly enriched for mutated genes. RESULTS: Ten studies fulfilled the inclusion criteria and were included in the analysis, for a total of 531 samples of MBMs evaluated. Twenty-seven genes were found recurrently mutated with a meta-analytic rate of SNVs higher than 5%. GSEA conducted on the list of these 27 recurrently mutated genes revealed vascular endothelial growth factor-activated receptor activity and transmembrane receptor protein tyrosine kinase activity to be among the top 10 gene ontology (GO) molecular functions significantly enriched for mutated genes, while regulation of apoptosis and cell proliferation were among the top 10 significantly enriched GO biological processes. Notably, a high meta-analytic rate of SNVs was found in several actionable cancer-associated genes, such as all the vascular endothelial growth factor (VEGF) receptor isoforms (i.e., Flt1 and Flt2 genes, for both SNV rate: 0.22, 95% CI 0.04-0.49; KDR gene, SNV rate: 0.1, 95% CI 0.05-0.16). Finally, two tumor suppressor genes were characterized by a high meta-analytic rate of CNVs: CDKN2A/B (CNV rate: 0.59, 95% CI 0.23-0.90) and PTEN (CNV rate: 0.31, 95% CI 0.02-0.95). CONCLUSION: MBMs harbored actionable molecular alterations that could be exploited as therapeutic targets to improve the poor prognosis of patients.

Miniaturized, high numerical aperture confocal fluorescence detection enhanced with pyroelectric droplet accumulation for sub-attomole analyte diagnosis.

To meet the growing demand for early fatal disease screening among large populations, current fluorescence detection instruments aiming at point-of-care diagnosis have the tendency to be low cost and high sensitivity, with a high potential for the analysis of low-volume, multiplex analytes with easy operation. In this work, we present the development of a miniaturized, high numerical aperture confocal fluorescence scanner for sub-micro-liter fluid diagnosis. It is enhanced with high-rate analyte accumulation using a pyroelectro-hydrodynamic dispensing system for generating tiny, stable sample droplets. The simplified confocal fluorescence scanner (numerical aperture 0.79, working distance 7.3 mm) uses merely off-the-shelf mass-production optical components. Experimental results show that it can achieve a high-sensitive, cost-efficient detection for sub-micro-liter, low-abundant (0.04 µL, 0.67 attomoles) fluid diagnosis, promising for point-of-care diagnosis.

Instant in situ formation of a polymer film at the water-oil interface.

The water-oil interface is an environment that is often found in many contexts of the natural sciences and technological arenas. This interface has always been considered a special environment as it is rich in different phenomena, thus stimulating numerous studies aimed at understanding the abundance of physico-chemical problems that occur there. The intense research activity and the intriguing results that emerged from these investigations have inspired scientists to consider the water-oil interface even as a suitable setting for bottom-up nanofabrication processes, such as molecular self-assembly, or fabrication of nanofilms or nano-devices. On the other hand, biphasic liquid separation is a key enabling technology in many applications, including water treatment for environmental problems. Here we show for the first time an instant nanofabrication strategy of a thin film of biopolymer at the water-oil interface. The polymer film is fabricated in situ, simply by injecting a drop of polymer solution at the interface. Furthermore, we demonstrate that with an appropriate multiple drop delivery it is also possible to quickly produce a large area film (up to 150 cm2). The film inherently separates the two liquids, thus forming a separation layer between them and remains stable at the interface for a long time. Furthermore, we demonstrate the fabrication with different oils, thus suggesting potential exploitation in different fields (e.g. food, pollution, biotechnology). We believe that the new strategy fabrication could inspire different uses and promote applications among the many scenarios already explored or to be studied in the future at this special interface environment.

Association of Anticancer Immune Checkpoint Inhibitors With Patient-Reported Outcomes Assessed in Randomized Clinical Trials: A Systematic Review and Meta-analysis.

Importance: The association of immune checkpoint inhibitors (ICIs) with patient quality of life has been poorly explored. Objective: To evaluate patient-reported outcomes (PROs) assessed in randomized clinical trials (RCTs) of immunotherapy-based treatments. Data Sources: This systematic review and random-effects meta-analysis used RCTs identified in PubMed, MEDLINE, Embase, and Scopus from database inception to June 1, 2021. Study Selection: A total of 2259 RCTs were identified that assessed ICIs as monotherapy or in combination with chemotherapy or combined with another ICI and/or targeted therapy vs control groups not containing immunotherapy in patients with advanced solid tumors. Studies were reviewed independently by 2 authors. Data Extraction and Synthesis: This meta-analysis followed the PRISMA guidelines and recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium. Main Outcomes and Measures: The coprimary aims of the meta-analysis were (1) pooled differences between treatment groups in the mean change of PRO score from baseline to 12 and 24 weeks of follow-up and (2) pooled differences between treatment groups in the time to deterioration of PRO score. For each end point, RCTs have been analyzed according to the type of treatment administered in the experimental group: ICIs given as monotherapy, ICIs combined with chemotherapy, or ICIs in association with another ICI and/or with targeted therapies. Results: Of the 2259 identified RCTs, 34 (18 709 patients) met the selection criteria and were analyzed. In the group of 19 RCTs testing ICIs as monotherapy, the pooled between-groups difference of mean change from baseline to 12 weeks of follow-up was 4.6 (95% CI, 2.8-6.4), and the mean change from baseline to 24 weeks of follow-up was 6.1 (95% CI, 4.2-8.1), significantly favoring ICIs. The pooled difference was 1.4 (95% CI, -0.4 to 3.2) at week 12 and 2.5 (95% CI, -0.8 to 5.9) at week 24 in the group of 8 RCTs testing ICIs combined with chemotherapy and 2.1 (95% CI, -0.8 to 5.0) at week 12 and 2.1 (95% CI, -0.4 to 4.5) at week 24 in the group of 8 RCTs testing other ICI-containing combinations. The time to deterioration was significantly longer in the immunotherapy-containing groups compared with control groups in all 3 groups of RCTs evaluated (hazard ratios of 0.80 [95% CI, 0.70-0.91] for ICIs as monotherapy, 0.89 [95% CI, 0.78-1.00] for ICIs plus chemotherapy, and 0.78 [95% CI, 0.63-0.96] for other ICI-containing combinations). Conclusions and Relevance: Immune checkpoint inhibitors as monotherapy appear to have a favorable association with patient-reported quality of life and can be combined with other classes of anticancer drugs without worsening this quality of life.

On-the-Fly Formation of Polymer Film at Water Surface.

The self-propulsion of bodies floating in water is of great interest for developing new robotic and intelligent systems at different scales, and whenever possible, Marangoni propulsion is an attractive candidate for the locomotion of untethered micro-robots. Significant cases have been shown using liquid and solid surfactants that allow an effective propulsion for bodies floating on water to be achieved. Here, we show for the first time a strategy for activating a twofold functionality where the self-propulsion of a floating body is combined with the formation of a polymer thin film at the water surface. In fact, we demonstrate that by using polymer droplets with an appropriate concentration of solvent and delivering such drops at specific locations onto freely floating objects, it is possible to form "on-the-fly" thin polymer films at the free water surface. By exploiting self-propulsion, a polymer thin film can be formed that could cover quite extensive areas with different shapes depending on the motion of the floating object. This intriguing twice-functionality activated though a single phenomenon, i.e., film formation and related locomotion, could be used in perspective to perform complex operations at water surfaces, such as dynamic liquid packaging, cleaning, and moving away floating particles, monolayer films, or macro-sized objects, as discussed in the text.

Extracorporeal membrane oxygenation (ECMO) in COVID-19 patients: a pocket guide for radiologists.

During the coronavirus disease 19 (COVID-19) pandemic, extracorporeal membrane oxygenation (ECMO) has been proposed as a possible therapy for COVID-19 patients with acute respiratory distress syndrome. This pictorial review is intended to provide radiologists with up-to-date information regarding different types of ECMO devices, correct placement of ECMO cannulae, and imaging features of potential complications and disease evolution in COVID-19 patients treated with ECMO, which is essential for a correct interpretation of diagnostic imaging, so as to guide proper patient management.

The Ubiquitin E3 Ligase TRIM21 Promotes Hepatocarcinogenesis by Suppressing the p62-Keap1-Nrf2 Antioxidant Pathway.

BACKGROUND AND AIMS: TRIM21 is a ubiquitin E3 ligase that is implicated in numerous biological processes including immune response, cell metabolism, redox homeostasis, and cancer development. We recently reported that TRIM21 can negatively regulate the p62-Keap1-Nrf2 antioxidant pathway by ubiquitylating p62 and prevents its oligomerization and protein sequestration function. As redox homeostasis plays a pivotal role in many cancers including liver cancer, we sought to determine the role of TRIM21 in hepatocarcinogenesis. METHODS: We examined the correlation between TRIM21 expression and the disease using publicly available data sets and 49 cases of HCC clinical samples. We used TRIM21 genetic knockout mice to determine how TRIM21 ablation impact HCC induced by the carcinogen DEN plus phenobarbital (PB). We explored the mechanism that loss of TRIM21 protects cells from DEN-induced oxidative damage and cell death. RESULTS: There is a positive correlation between TRIM21 expression and HCC. Consistently, TRIM21-knockout mice are resistant to DEN-induced hepatocarcinogenesis. This is accompanied by decreased cell death and tissue damage upon DEN treatment, hence reduced hepatic tissue repair response and compensatory proliferation. Cells deficient in TRIM21 display enhanced p62 sequestration of Keap1 and are protected from DEN-induced ROS induction and cell death. Reconstitution of wild-type but not the E3 ligase-dead and the p62 binding-deficient mutant TRIM21 impedes the protection from DEN-induced oxidative damage and cell death in TRIM21-deficient cells. CONCLUSIONS: Increased TRIM21 expression is associated with human HCC. Genetic ablation of TRIM21 leads to protection against oxidative hepatic damage and decreased hepatocarcinogenesis, suggesting TRIM21 as a preventive and therapeutic target.

Jejunoileal diverticula: a broad spectrum of complications.

BACKGROUND: Small bowel diverticula are a rare condition occurring mainly in the elderly. They can be isolated or multiple and can involve the duodenum, jejunum and ileum. Acute complications are extremely rare, with an aspecific pattern of symptoms. The aim of the study is to report the different patterns of presentation of patients with complicated jejunoileal diverticula. METHODS: This is a retrospective descriptive study on a consecutive series of patients admitted for complicated jejunoileal diverticula in four Italian surgical departments between 2012 and 2019. Complications included acute diverticulitis, bleeding, perforation and intestinal obstruction. Patients presenting with complicated duodenal or Meckel's diverticula were not included. RESULTS: Twenty-six patients were enrolled. The median age was 77 (46-94) years. Abdominal pain, fever and nausea/vomiting were the most frequent symptoms at presentation. Abdominal computed tomography (CT) was diagnostic in 35% of patients. Ten (38%) patients had bowel perforation, nine (35%) acute diverticulitis, five (19%) bowel obstruction and two (8%) had intestinal bleeding. Twenty-one (81%) patients underwent surgery, two (8%) were managed by CT-guided drainage of collections and three (11%) were treated with antibiotics. One patient died post-operatively. The median hospital stay was 9 (5-62) days. CONCLUSION: Acutely complicated jejunoileal diverticula are infrequent, but a strong suspect should be raised whenever elderly patients are admitted for unspecific abdominal pain with a non-diagnostic CT scan. Conservative management may be offered in very selected cases if a diagnosis is obtained, but in most instances, surgery is both diagnostic and therapeutic.

Quick liquid packaging: Encasing water silhouettes by three-dimensional polymer membranes.

One of the most important substances on Earth is water. It is an essential medium for living microorganisms and for many technological and industrial processes. Confining water in an enclosed compartment without manipulating it or by using rigid containers can be very attractive, even more if the container is biocompatible and biodegradable. Here, we propose a water-based bottom-up approach for facile encasing of short-lived water silhouettes by a custom-made adaptive suit. A biocompatible polymer self-assembling with unprecedented degree of freedom over the water surface directly produces a thin membrane. The polymer film could be the external container of a liquid core or a free-standing layer with personalized design. The membranes produced have been characterized in terms of physical properties, morphology and proposed for various applications from nano- to macroscale. The process appears not to harm cells and microorganisms, opening the way to a breakthrough approach for organ-on-chip and lab-in-a-drop experiments.

On the Complex and Reversible Pathways of CdSe Quantum Dots Driven by Pyroelectric-Dielectrophoresis.

Electrophoresis (EP) and dielectrophoresis (DEP) are the two well-established methodologies to manipulate nanoparticles (NPs). Recently, DEP by a virtual electrode platform was demonstrated on ferroelectric substrates, where the driving force is due to the strong electric field generated by the pyroelectric effect, thus opening new scenarios for manipulating the matter. Such an innovative approach named pyroelectric-DEP has several advantages over traditional EP and DEP. However, a detailed study on this novel approach is required for understanding the complex pathways traced by NPs under the action of the pyroelectric-driven forces and thus for explaining the final patterns. Here, we investigate experimentally the dynamic behavior of CdSe NPs through time-lapse fluorescence microscopy imaging. Complete visualization and measurement of the directed-assembling process of NPs immersed in polydimethylsiloxane fluid is reported, which shows some unpredicted results with respect to the previous works, thus opening the route for designing in principle a reversible and switchable device allowing two different and reversible final NP-patterned states. The observed phenomena are fully analyzed by experimental and simulated analysis, and the movements of NPs is performed to elucidate in depth the involved processes. The investigation furnishes an interesting result that the complex behavior of the NPs can be fully comprehended and explained by considering the superposition of both EP and DEP forces.

Factors Associated with the Economic Sustainability of the Registered Dental Hygienist in Alternative Practice.

Purpose: The purpose of this study was to investigate key factors associated with the economic sustainability of the Registered Dental Hygienist in Alternative Practice (RDHAP).Methods: An invitation to participate in a 38-question electronic survey was sent via postal mail to 440 RDHAP licentiate addressees obtained through the Dental Hygiene Committee of California (DHCC). Legal restrictions did not allow for obtaining the RDHAP licentiate email addresses from the DHCC. The survey was disseminated via email to the 254 RDHAPs who were members of the California Dental Hygienists' Association. Additional invitations to participate were made via flyer distribution at an RDHAP symposium, and on RDHAP only social media sites.Results: The response rate was an estimated 16%. While 44% of the RDHAPs reported some employment in a traditional dental practice, given the opportunity, 61% of these respondents indicated that they would practice exclusively as an RDHAP. With regard to practice strategic planning and alliances, 31% felt that dentists lacked knowledge of the RDHAP, and 25% indicated dentists were resistant to this workforce model. Regarding RDHAP practice staffing patterns, 75% indicated not having any employees. When asked about business systems, 64% had solo, portable practices and 16% had standalone practices. Economic sustainability challenges included practice business/equipment expenses (29%), insurance/reimbursement issues (21%), patient flow (19%) and RDHAP visibility (14%).Conclusions: RDHAP practices face challenges including the need for strategic planning and intra- and inter-professional alliances, efficient and effective patient flow, optimal staffing patterns and effective business systems. Focus on enhancing RDHAP visibility within the dental and medical communities should be a priority. In addition, further research should explore RDHAPs aligning with community-based clinics, Federally Qualified Health Centers and Dental Support Organizations (DSOs) with a commitment to disease prevention in addition to the financial resources and staff to manage practice business systems.

Direct Writing of Microfluidic Footpaths by Pyro-EHD Printing.

In this study, we report a direct writing method for the fabrication of microfluidic footpaths by pyro-electrohydrodynamic (EHD) jet printing. Here, we propose the use of a nozzle-free three-dimensional printing technique for the fabrication of printed structures that can be embedded in a variety of soft, transparent, flexible, and biocompatible polymers and thus easily integrated into lab-on-chip devices. We prove the advantage of the high resolution and flexibility of pyro-EHD printing for the realization of microfluidic channels well below the standard limit in dimension of conventional ink-jet printing technique and simply adaptable to the end-user desires in terms of geometry and materials. Starting from the description of the innovative approach proposed for the channel fabrication, we demonstrate the design, fabrication, and proof of a microfluidic matrix of interconnected channels. The method described here could be a breakthrough technology for the fabrication of in situ implantable, stretchable, and biocompatible devices, opening new routes in the field of biomedical engineering and wearable electronics.

Demanding Diagnosis of Splenic Angiosarcoma as Cause of Delayed Treatment of Spontaneous Splenic Rupture: A Case Report and Literature Review.

Background. Primary splenic angiosarcoma is a very rare mesenchymal malignant tumor associated with a poor prognosis due to its high metastatic potential. This disease can be easily neglected and spontaneous splenic rupture is a frequent manifestation at the time of diagnosis leading to a poor outcome because of peritoneal dissemination. Case Presentation. We describe the case of a 49-year-old man who presented with asthenia, left upper quadrant abdominal pain, and anemia. Computerized tomography scan showed an enlarged spleen with no nodules and a nontraumatic rupture of the splenic capsule. Splenectomy was performed on account of the severe anemia and histopathology examination showed a primary angiosarcoma. Conclusions. Splenic angiosarcoma should be considered as one of the differential diagnoses in patients with nontraumatic spleen rupture and a specific previous medical history. Regrettably, splenectomy allows for a definitive diagnosis but not a curative treatment.

Endowing a plain fluidic chip with micro-optics: a holographic microscope slide.

Lab-on-a-Chip (LoC) devices are extremely promising in that they enable diagnostic functions at the point-of-care. Within this scope, an important goal is to design imaging schemes that can be used out of the laboratory. In this paper, we introduce and test a pocket holographic slide that allows digital holography microscopy to be performed without an interferometer setup. Instead, a commercial off-the-shelf plastic chip is engineered and functionalized with this aim. The microfluidic chip is endowed with micro-optics, that is, a diffraction grating and polymeric lenses, to build an interferometer directly on the chip, avoiding the need for a reference arm and external bulky optical components. Thanks to the single-beam scheme, the system is completely integrated and robust against vibrations, sharing the useful features of any common path interferometer. Hence, it becomes possible to bring holographic functionalities out of the lab, moving complexity from the external optical apparatus to the chip itself. Label-free imaging and quantitative phase contrast mapping of live samples are demonstrated, along with flexible refocusing capabilities. Thus, a liquid volume can be analyzed in one single shot with no need for mechanical scanning systems.

Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials.

The role of glutamine (GLN) supplementation in critically ill patients is controversial. Our aim was to analyze its potential effect in patients admitted to intensive care unit (ICU).We performed a systematic literature review through Medline, Embase, Pubmed, Scopus, Ovid, ISI Web of Science, and the Cochrane-Controlled Trials Register searching for randomized clinical trials (RCTs) published from 1983 to 2014 and comparing GLN supplementation to no supplementation in patients admitted to ICU. A random-effect meta-analysis for each outcome (hospital and ICU mortality and rate of infections) of interest was carried out. The effect size was estimated by the risk ratio (RR).Thirty RCTs were analyzed with a total of 3696 patients, 1825 (49.4%) receiving GLN and 1859 (50.6%) no GLN (control groups). Hospital mortality rate was 27.6% in the GLN patients and 28.6% in controls with an RR of 0.93 (95% CI = 0.81-1.07; P = 0.325, I = 10.7%). ICU mortality was 18.0 % in the patients receiving GLN and 17.6% in controls with an RR of 1.01 (95% CI = 0.86-1.19; P = 0.932, I = 0%). The incidence of infections was 39.7% in GLN group versus 41.7% in controls. The effect of GLN was not significant (RR = 0.88; 95% CI = 0.76-1.03; P = 0.108, I = 56.1%).These results do not allow to recommend GLN supplementation in a generic population of critically ills. Further RCTs are needed to explore the effect of GLN in more specific cohort of patients.