Development of a whole spinal MRI-based tumor burden scoring method in participants with multiple myeloma: a pilot study of prognostic significance.

The aim of the study was to develop a new whole spinal MRI-based tumor burden scoring method in participants with newly diagnosed multiple myeloma (MM) and to explore its prognostic significance. We prospectively recruited participants with newly diagnosed MM; performed whole spinal MRI (sagittal FSE T1WI, sagittal IDEAL T2WI, and axial FLAIR T2WI) on them; and collected their clinical data, early treatment response, progression-free survival (PFS), and overall survival (OS). We developed a new tumor burden scoring method according to the extent of bone marrow infiltration in five MRI patterns. All participants were divided into good response and poor response groups after four treatment cycles. Univariate, multivariate analyses, and ROC were used to determine the performance of independent predictors. Thresholds for PFS and OS were calculated using X-tile, and their prognostic significance were assessed by Kaplan-Meier. The Kruskal-Wallis H test was used to compare the differences of tumor burden score between the revised International Staging System (R-ISS) stages. The new tumor burden scoring method was used in 62 participants (median score, 12; range, 0-18). The tumor burden score (OR 1.266, p = 0.002) was an independent predictor of poor response and the AUC was 0.838. Higher tumor burden scores were associated with shorter PFS (p = 0.002) and OS (p = 0.011). The tumor burden score was higher in R-ISS-III than in R-ISS-I and R-ISS-II (p = 0.016 and p = 0.006, respectively). The tumor burden score was an excellent predictor of prognosis and may serve as a supplemental marker for R-ISS.

Omental coating attenuates implant-induced foreign body reaction in rats.

The objective of this study is to clarify whether the omental coating can effectively attenuate foreign body reaction (FBR) induced by implanted materials. Male Sprague-Dawley rats were injected with polydextran particle slurry intraperitoneally to activate the omentum. 7 days later, polyether polyurethane sponge discs were implanted subcutaneously on each side of the rat's back as the foreign implants to induce FBR. The next day, omental transposition were performed. The disc on the left side of each rat's back was wrapped with omental flap (omental group); the disc on the right side was untreated (control group). All discs were removed 21 days after implantation and assessed by determining the components of the fibrovascular tissue (angiogenesis, inflammation, foreign body giant cells (FBGCs) aggregation and fibrogenesis). In implants in omental group, micro vessel density (MVD), Hemoglobin (Hb) content and VEGF levels (pro-angiogenic cytokine) were increased when compared with implants from control group. Inflammatory parameters (IL-1ß; macrophage accumulation-NAG activity; neutrophil accumulation- MPO levels) were decreased in implants after omental coating. Also, collagen deposition, fibrous capsule thickness, and FBGCs decreased in implants from omental group. However, intra-implant levels of TNF-α and TGF-ß1 were not different after omental coating. Our findings showed for the first time that the omental coating around the implants attenuate the adverse FBR, it may be critical in developing new strategies to control FBR and improve the function and performance of the implanted materials.

Identification and profile of phenolamides with anthracnose resistance potential in tea (Camellia sinensis).

Tea anthracnose is a prevalent disease in China that can lead to reduced tea production and lower quality, yet there is currently a lack of effective means for controlling this disease. In this study, we identified 46 phenolamides (including 27 isomers) in different tissues and organs of tea plants based on a developed workflow, and the secondary mass spectra of all these compounds have been documented. It was revealed that tea plants predominantly accumulate protonated aliphatic phenolamides, rather than aromatic phenolamides. The profile of phenolamides indicate that their buildup in tea plants is specific to certain tissues and acyl-acceptors, and this distribution is associated with the extent of phenolamide acyl-modification. Additionally, it was observed that N-Feruloylputrescine (Fer-Put, a type of phenolamides) was responsive to the stimulated accumulation of the tea anthracnose pathogen. The findings of anti-anthracnose experiments in vitro and on tea leaf demonstrated that Fer-Put was capable of significantly inhibiting the growth of anthracnose pathogen colony, effectively prevented tea leaf disease. Furthermore, it was observed that Fer-Put treatment can enhance the antioxidant enzyme activity of tea leaves. TEA002780.1 and TEA013165.1 gene may be responsible for the biosynthesis of Fer-Put in the disease resistance process in tea plants. Through these studies, the types and distribution of phenolamides in tea plants have been elucidated, and Fer-Put's ability to resist anthracnose has been established, providing new insights into the resistance of tea anthracnose.

A Fast Magnetic Flux Density Measurement Method With Skip-Echo Acquired Turbo Spin Echo (SATE).

The measurements of magnetic flux density ( Bz) needed in magnetic resonance electrical impedance tomography (MREIT) and magnetic resonance current density imaging (MRCDI) techniques often utilize spin echo (SE)-based sequences for data acquisition. The low imaging speed of SE-based methods significantly hampers the clinical applications of MREIT and MRCDI. Here, we propose a new sequence for substantially accelerating the acquisition of Bz measurements. A skip-echo acquired turbo spin echo (SATE) imaging sequence based on the conventional turbo spin echo (TSE) technique was proposed by adding a skip-echo module in front of the TSE acquisition module. The skip-echo module consisted of a series of refocusing pulses without acquisition. In SATE, amplitude-modulated crusher gradients were used to remove the stimulated echo pathways, and the radiofrequency (RF) pulse shape was specially selected to preserve more signals. In efficiency evaluation experiments performed on a spherical gel phantom, we demonstrated that SATE had improved measurement efficiency compared to the conventional TSE sequence via skipping one echo before acquiring signals. The accuracy of the Bz measurements by SATE was validated against those by the multi-echo injection current nonlinear encoding (ME-ICNE) method, while SATE was able to accelerate the data acquisition up to 10-fold. Volumetric coverage of Bz maps obtained in the phantom, pork, and human calf illustrated that SATE can reliably measure volumetric Bz distributions within clinically acceptable time. The proposed SATE sequence provides a fast and effective approach for volumetric coverage of Bz measurements, greatly facilitating the clinical applications of MREIT and MRCDI techniques.

Single-cell analysis reveals melanocytes may promote inflammation in chronic wounds through cathepsin G.

During acute wound (AW) healing, a series of proper communications will occur between different epidermal cells at precise temporal stages to restore the integrity of the skin. However, it is still unclear what variation happened in epidermal cell interaction in the chronic wound environment. To provide new insights into chronic wound healing, we reconstructed the variations in the epidermal cell-cell communication network that occur in chronic wound healing via single-cell RNA-seq (scRNA-seq) data analysis. We found that the intricate cellular and molecular interactions increased in pressure ulcer (PU) compared to AW, especially the PARs signaling pathways were significantly upregulated. It shows that the PARs signaling pathways' main source was melanocytes and the CTSG-F2RL1 ligand-receptor pairs were its main contributor. Cathepsin G (CatG or CTSG) is a serine protease mainly with trypsin- and chymotrypsin-like specificity. It is synthesized and secreted by some immune or non-immune cells. Whereas, it has not been reported that melanocytes can synthesize and secrete the CTSG. F2R Like Trypsin Receptor 1 (F2RL1) is a member of proteinase-activated receptors (PARs) that are irreversibly activated by proteolytic cleavage and its stimulation can promote inflammation and inflammatory cell infiltration. In this study, we found that melanocytes increased in pressure ulcers, melanocytes can synthesize and secrete the CTSG and may promote inflammation in chronic wounds through CTSG-F2RL1 pairs, which may be a novel potential target and a therapeutic strategy in the treatment of chronic wounds.

Imaging Techniques and Clinical Application of the Marrow-Blood Barrier in Hematological Malignancies.

The pathways through which mature blood cells in the bone marrow (BM) enter the blood stream and exit the BM, hematopoietic stem cells in the peripheral blood return to the BM, and other substances exit the BM are referred to as the marrow-blood barrier (MBB). This barrier plays an important role in the restrictive sequestration of blood cells, the release of mature blood cells, and the entry and exit of particulate matter. In some blood diseases and tumors, the presence of immature cells in the blood suggests that the MBB is damaged, mainly manifesting as increased permeability, especially in angiogenesis. Some imaging methods have been used to monitor the integrity and permeability of the MBB, such as DCE-MRI, IVIM, ASL, BOLD-MRI, and microfluidic devices, which contribute to understanding the process of related diseases and developing appropriate treatment options. In this review, we briefly introduce the theory of MBB imaging modalities along with their clinical applications.

De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids.

Hematopoietic humanized (hu) mice are powerful tools for modeling the action of human immune system and are widely used for preclinical studies and drug discovery. However, generating a functional human T cell compartment in hu mice remains challenging, primarily due to the species-related differences between human and mouse thymus. While engrafting human fetal thymic tissues can support robust T cell development in hu mice, tissue scarcity and ethical concerns limit their wide use. Here, we describe the tissue engineering of human thymus organoids from inducible pluripotent stem cells (iPSC-thymus) that can support the de novo generation of a diverse population of functional human T cells. T cells of iPSC-thymus-engrafted hu mice could mediate both cellular and humoral immune responses, including mounting robust proinflammatory responses on T cell receptor engagement, inhibiting allogeneic tumor graft growth and facilitating efficient Ig class switching. Our findings indicate that hu mice engrafted with iPSC-thymus can serve as a new animal model to study human T cell-mediated immunity and accelerate the translation of findings from animal studies into the clinic.

CT-Angiography-Based Outcome Prediction on Diabetic Foot Ulcer Patients: A Statistical Learning Approach.

The purpose of our study is to predict the occurrence and prognosis of diabetic foot ulcers (DFUs) by clinical and lower extremity computed tomography angiography (CTA) data of patients using the artificial neural networks (ANN) model. DFU is a common complication of diabetes that severely affects the quality of life of patients, leading to amputation and even death. There are a lack of valid predictive techniques for the prognosis of DFU. In clinical practice, the use of scales alone has a large subjective component, leading to significant bias and heterogeneity. Currently, there is a lack of evidence-based support for patients to develop clinical strategies before reaching end-stage outcomes. The present study provides a novel technical tool for predicting the prognosis of DFU. After screening the data, 203 patients with diabetic foot ulcers (DFUs) were analyzed and divided into two subgroups based on their Wagner Score (138 patients in the low Wagner Score group and 65 patients in the high Wagner Score group). Based on clinical and lower extremity CTA data, 10 predictive factors were selected for inclusion in the model. The total dataset was randomly divided into the training sample, testing sample and holdout sample in ratio of 3:1:1. After the training sample and testing sample developing the ANN model, the holdout sample was utilized to assess the accuracy of the model. ANN model analysis shows that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of the overall ANN model were 92.3%, 93.5%, 87.0%, 94.2% and 0.955, respectively. We observed that the proposed model performed superbly on the prediction of DFU with a 91.6% accuracy. Evaluated with the holdout sample, the model accuracy, sensitivity, specificity, PPV and NPV were 88.9%, 90.0%, 88.5%, 75.0% and 95.8%, respectively. By contrast, the logistic regression model was inferior to the ANN model. The ANN model can accurately and reliably predict the occurrence and prognosis of a DFU according to clinical and lower extremity CTA data. We provided clinicians with a novel technical tool to develop clinical strategies before end-stage outcomes.

Efficacy and safety of CO2 laser in the treatment of chronic wounds: A Retrospective Matched Cohort Trial.

OBJECTIVES: Treating chronic cutaneous wounds is challenging, and debridement is a central concept in treating them. Studies have shown that CO2 laser debridement can control local infection and promote the wound healing process. The present study aimed to investigate the efficacy and safety of fully ablative CO2 laser debridement compared to routine surgical debridement in the treatment of chronic wounds. METHODS: The retrospective cohort study was conducted on patients with chronic (>1 month) cutaneous wounds (≥1 cm2 ) between December 1, 2017, and December 1, 2020, in the Wound Healing Center at Shanghai Ruijin Hospital, China. Patients treated with CO2 laser debridement with a DEKA SmartXide2 C80 (DEKA) (the CO2 laser group) were compared with matched control patients with similar baseline characteristics who had undergone routine surgical debridement (the routine group). The primary outcome was time-to-heal (days) for chronic wounds in two groups, and secondary outcomes included the wound area and BWAT (Bates-Jensen wound assessment tool) score before treatment, and at 1, 2, 3, and 4 weeks after treatment. RESULTS: The study included 164 patients (82 in the CO2 laser group and 82 matched in the routine group). The time-to-heal for patients in the CO2 laser group (41.30 ± 17.11) was significantly shorter than that of the patients in the routine group (48.51 ± 24.32) (p = 0.015). At 3 and 4 weeks after treatment, the absolute wound area of the CO2 laser group was significantly smaller than that of the routine group. Also, the CO2 laser group exhibited a significantly lower relative area at 2, 3, and 4 weeks after treatment. The CO2 laser group yielded significantly lower BWAT scores at 2, 3, and 4 weeks after treatment. Additionally, the relative BWAT score was significantly lower in the CO2 laser group than the relative scores in the routine group at 2, 3, and 4 weeks after treatment. No adverse events related to the treatments were observed in either group during the study period. CONCLUSIONS: The present study has shown that fully ablative CO2 laser debridement has several advantages over routine sharp surgical debridement. It is superior at ameliorating wound status and reducing wound area, and it also significantly reduces the time-to-heal for chronic wounds, without causing any adverse events.

Application of Compound Polymyxin B Ointment in the Treatment of Chronic Refractory Wounds.

The purpose of this study was to investigate the clinical efficacy of compound polymyxin B ointment for treating chronic refractory wounds. A retrospective analysis was performed on 111 patients who underwent chronic refractory wound treatment. Patients were divided into 2 groups, with 45 patients included in the experimental group (compound polymyxin B group) and 66 patients included in the control group (silver sulfadiazine group). After thorough debridement in both groups, either compound polymyxin B ointment or silver sulfadiazine cream was evenly applied to the patient's wound and covered with sterile gauze. In both groups, dressing changes were dependent on the wound's condition and secretions. Using the Bates-Jensen Wound Assessment Tool (BWAT), patients in both groups were scored, after which wound healing, infection, and healing time were compared. There was no significant difference in BWAT scores between the 2 groups on the 7th or 14th day; however, on the 21st day, the BWAT score in the experimental group was significantly lower than that of the control group. The difference was statistically significant (P < .05). There was no significant difference in the BWAT-I scores between the 2 groups on the seventh day. The healing time in the experimental group was significantly shorter than that of the control group, and the difference was statistically significant (P < .05). For the treatment of chronic refractory wounds, thorough debridement followed by compound polymyxin B ointment topical application can reduce and control wound infection effectively and accelerate the process of wound repair.

Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to facilitate tissue repair in diabetic wounds.

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO-induced dysfunction. We observed that the accumulation of MGO-derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO-derived AGEs in the wound tissue of type-2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1-like macrophages induced by lipopolysaccharide (LPS), but not those of M0-like macrophages induced by PMA or of M2-like macrophages induced by interleukins 4 (IL-4) and 13 (IL-13); the impaired phagocytosis of M1-like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non-healing diabetic wounds.

Successful Postoperative Nephrocutaneous Fistula Treatment With Omental Flap Grafting: A Case Report.

Nephrocutaneous fistula (NCF) is a rare and severe complication of renal disease and surgical procedures. Treatments for NCF are based on the renal function, and can include nephrectomy, heminephrectomy, nephroureterectomy, endourological maneuvers or antibiotic therapy alone. Here we report a case of a chronic NCF which occurred 5 years after partial nephrectomy. In this report, we describe a new surgical approach for the management of a patient with postoperative NCF. In the present case, in addition to removing the fistulous tract, we also performed an omental flap grafting to tightly cover the kidney. In addition to limiting and controlling the local inflammation, the omental flap prevents contact between the kidney and the flank muscle on its posterior rim. No recurrence or complications occurred throughout 10 months of follow-up. The NCF was successfully treated with completely removal of the sinus tract and omental flap grafting, without nephrectomy. This case adds new aspects to the treatment of NCF.

An Optimization Approach for Transcranial Direct Current Stimulation Using Nondominated Sorting Genetic Algorithm II.

Transcranial direct current stimulation (tDCS) delivers weak current into the brain to modulate neural activities. Many methods have been proposed to determine electrode positions and stimulation intensities. Due to the trade-off between intensity and focality, it is actually a multi-objective optimization problem that has a set of optimal solutions. However, traditional methods can produce only one solution at each time, and many parameters need to be determined by experience. In this study, we proposed the nondominated sorting genetic algorithm II (NSGA-II) to solve the current optimization problem of multi-electrode tDCS. We also compared the representative solutions with LCMV solutions. The result shows that a group of solutions close to the optimal front can be obtained just in only one run without any prior knowledge.

Distribution and Antibiotic Resistance Patterns of Pathogenic Bacteria in Patients With Chronic Cutaneous Wounds in China.

Background: To determine the distribution and antimicrobial susceptibility pattern of pathogenic bacteria in patients with chronic cutaneous wounds on a national scale. Methods: A retrospective study was conducted using the data recorded between January 1, 2018 and January1, 2020 in 195 hospitals across China. After screening the data, 815 patients with chronic wounds were finally analyzed. The data collected included information about the patients' general condition and local cutaneous wound assessments, especially microbial culture and antibiotic susceptibility tests. The analyses were performed using SPSS Version 26. Results: The study included 815 patients (290 [35.6%] females; 63 [50-74] years). The most common causes of chronic cutaneous wounds were diabetes (183, 22.5%), infection (178, 21.8%), and pressure (140, 17.2%). Among these, 521(63.9%) samples tested yielded microbial growth, including 70 (13.4%) polymicrobial infection and 451 (86.6%) monomicrobial infection. The positive rate of microbial culture was highest in wound tissue of ulcers caused by infection (87.6%), followed by pressure (77.1%), diabetes (68.3%), and venous diseases (67.7%). Bates-Jensen wound assessment tool (BWAT) scores >25 and wounds that lasted for more than 3 months had a higher positive rate of microbial culture. BWAT scores >25 and wounds in the rump, perineum, and feet were more likely to exhibit polymicrobial infection. A total of 600 strains were isolated, of which 46.2% (277 strains) were Gram-positive bacteria, 51.3% (308 strains) were Gram-negative bacteria, and 2.5% (15 strains) were fungi. The most common bacterial isolates were Staphylococcus aureus (29.2%), Escherichia coli (11.5%), Pseudomonas aeruginosa (11.0%), Proteus mirabilis (8.0%), and Klebsiella pneumoniae (5.8%). The susceptibility tests showed that 116 cultured bacteria were Multidrug resistant (MDR) strains. The resistance rates of S. aureus were 92.0% (161/175) to penicillin, 58.3% (102/175) to erythromycin, and 50.9% (89/175) to clindamycin. Vancomycin was the most effective antibiotic (0% resistance rate) against all Gram-positive bacteria. Besides, the resistance rates of E. coli were 68.1% (47/69) to ampicillin, 68.1% (47/69) to ciprofloxacin, 60.9% (42/69) to levofloxacin. However, all the isolated Gram-negative bacteria showed low resistance rates to tigecycline (3.9%) and amikacin (3.6%). Conclusions: The distribution of bacteria isolated from chronic cutaneous wounds varies with the BWAT scores, causes, duration, and the location of wounds. Multidrug resistance is a serious health issue, and therefore antibiotics used in chronic wounds must be under strict regulation. Our findings may help clinicians in making informed decisions regarding antibiotic therapy.

Effect of Long-term Transcranial Direct Current Stimulation on Glx and GABA: A Pilot Study.

Previous studies have demonstrated that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) can enhance working memory. However, the mechanism underlying the long-term tDCS is still unclear. This pilot study aims to examine neurotransmitters such as gamma-aminobutyric (GABA) and Glx (a measure of glutamate and glutamine combined) and working memory in response to the long-term anodal tDCS over dlPFC. Six healthy, right-handed young adults enrolled in this study received 2-mA anodal tDCS over dlPFC within 4 weeks. Long-term tDCS means that it was applied 5 times per week for the first two weeks and once for the last two weeks with 30 min each time. The other six participants were enrolled as the control group without stimulation for testing the baseline enhancement of working memory due to learning. The GABA and Glx levels were assessed by Magnetic Resonance Spectroscopy (MRS), while a 3-back task was performed to assess working memory. Data were collected at the beginning of the experiment, after two-week tDCS and at the end of the experiment. We found that the working memory was not significantly enhanced by the first two-week tDCS because the accuracy of response in 3-back was not significantly increased compared to the control group. Meanwhile, there were no significant changes in the levels of GABA. However, the Glx level was found significantly decreased in both 2- and 4-week MRS measurements. The observation that the long-term tDCS causes the decrease of excitatory neurotransmitters implies the different underlying mechanisms between the long-term tDCS and the single one.

Validation of Numerical Simulation for Transcranial Direct Current Stimulation with Spherical Phantom.

Transcranial direct current stimulation (tDCS) is a promising brain modulation technique in clinical application. Computational models of brain current flow have been used to provide better insights into determining the stimulation parameters, but there are only a few studies to validate the numerical simulation model. The purpose of this study is to validate the simulation model of tDCS. A one-/three-layered spherical phantom model was constructed to mimic the human head. The tDCS-induced voltages were measured at different depth in the spherical phantom model with stereotactic-EEG (s-EEG) electrodes. Comparing the measured values with the simulation data from the computational models, we found that the computational and empirically measured electric field distributions on the brain surface is similar and that the deviation between the predicted and measured electric field value becomes larger near the electrode.

Effect of miR-181a-3p on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting BMP10.

Objective: To explore the regulation relationship between miR-181a-3p and BMP10, and their mechanism of osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs).Methods: After osteogenic induction of MSCs, the ALP activity was detected by ELISA. The expression of miRNA-181a-3p and BMP10 was detected by RT-qPCR, and the protein levels of BMP10 and osteogenic differentiation marker proteins ALK and RUNX2 were detected by Western blot. The TargetScan online website was used to predict the putative target of miR-181a-3p, and dual luciferase reporter assay was performed to validate the targeting relationship between miR-181a-3p and BMP10.Results: In osteogenic differentiation of MSCs, ALP activity, the level of ALK and RUNX2 was evidently increased (p < .05), and the expression of miR-181a-3p was significantly downregulated (p < .05). Moreover, overexpression of miR-181a-3p obviously decreased the expression of BMP10 (p < .05), miR-181a-3p knockdown increased the expression of BMP10 prominently (p < .05). The transfection of miR-181a-3p mimics resulted in significantly downregulation of ALP activity and RUNX2 protein expression in MSCs (p < .05). In addition, overexpression of BMP10 could reverse the inhibitory effect of miR-181a-3p on osteogenic differentiation (p < .05).Conclusions: In conclusion, we found that miR-181a-3p inhibited osteogenic differentiation of MCSs by targeting BMP10.

Effects of Enteral Immunonutrition in Patients Undergoing Pancreaticoduodenectomy: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effect of enteral immunonutrition (EIN) in patients undergoing pancreaticoduodenectomy (PD) is still doubtful. This meta-analysis aimed to assess the impact of EIN on postoperative clinical outcomes for patients undergoing PD. METHODS: A literature search was carried out to identify all of the randomized controlled trials (RCTs) concerning the use of EIN for PD. Data collection ended on April 1, 2018. Pooled risk ratios (RRs) and the mean difference (MD) with a 95% CI were calculated using fixed effects or random effects models. The analyses were performed with RevMan 5.3.5. RESULTS: Four RCTs with a total of 299 patients were included. Immunonutrition reduced the incidence of postoperative infectious complications (RR 0.58, 95% CI 0.37-0.92; p = 0.02) and shortened the length of hospital stay (MD -1.79, 95% CI -3.40 to 0.18; p = 0.03). Conversely, there were no significant differences in the incidence of overall postoperative complications (RR 0.81, 95% CI 0.62-1.05; p = 0.11), non-infectious complications (RR 0.94, 95% CI 0.69-1.28; p = 0.70) and postoperative mortality (RR 2.43, 95% CI 0.37-16.10; p = 0.36). CONCLUSIONS: EIN reduced postoperative infectious complications and shortened the length of the hospital stay; immunonutrition should be encouraged in patients undergoing PD.