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Ngoc Quyen Nguyen,1 Trong Hau Phan2 1Department of Outpatient Clinic, 108 Military Central Hospital, Hanoi City, Vietnam; 2Department of Spinal Surgery, 108 Military Central Hospital, Hanoi City, VietnamCorrespondence: Ngoc Quyen Nguyen, Department of Outpatient Clinic, 108 Military Central Hospital, No. 1, Tran Hung Dao Street, Ha Ba Trung District, Hanoi City, 113000, Vietnam, Tel +84-989052288, Email bsquyenptcs108@gmail.comIntroduction: Postoperative surgical site infection remains one of the major complications after spinal surgery. IntraSPINE® (intraspine) is a dynamic intralaminar device introduced by Cousin Biotech and is indicated for the surgical treatment of lumbar spine disorders. There are no reports on delayed surgical site infection (SSI) after lumbar surgery using this device.Case Presentation: A 29-year-old male patient was admitted to our department with complaints of moderate pain and chronic subcutaneous abscess with purulent flow from his old surgical scar. Thirty-four months ago, he underwent a traditional open bilateral L4 laminotomy without discectomy and intraspine insertion for the treatment of L4-5 central lumbar spinal stenosis at another hospital. The patient was discharged 4 days after surgery without radiating pain, and the surgical wound was well healed. He gradually returned to his normal activity and work. However, he experienced moderate pain, redness and swelling of his old surgical scar approximately one month before coming to our hospital, but he did not receive any treatment. One month later, he had a mass with purulent discharge at the surgical scar site, and he visited our hospital on December 29th, 2020. Based on the physical examination and MRI findings, delayed -SSI was diagnosed. The patient underwent removal of the intraspine device, debridement and wound closure with closed drainage. The wound healed satisfactorily, and the patient had no complaints more than 2 years later.Conclusion: A delayed surgical site infection following intraspine insertion may have occurred.Keywords: postoperative surgical infection, artificial device, lumbar disc herniation

Minh-Hoang Tran,1 Ngoc Quy Nguyen,2 Hong Tham Pham1,3 1Department of Pharmacy, Nhan Dan Gia Dinh Hospital, Ho Chi Minh City, Vietnam; 2Institute of Environmental Technology and Sustainable Development, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam; 3Department of Pharmacy, Nguyen Tat Thanh University, Ho Chi Minh City, VietnamCorrespondence: Hong Tham Pham, Department of Pharmacy, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam, Tel +84 919 559 085, Email phtham@ntt.edu.vnAbstract: Recent years have witnessed the rise of artificial intelligence (AI) in antimicrobial resistance (AMR) management, implying a positive signal in the fight against antibiotic-resistant microbes. The impact of AI starts with data collection and preparation for deploying AI-driven systems, which can lay the foundation for some effective infection control strategies. Primary applications of AI include identifying potential antimicrobial molecules, rapidly testing antimicrobial susceptibility, and optimizing antibiotic combinations. Aside from their outstanding effectiveness, these applications also express high potential in narrowing the burden gap of AMR among different settings around the world. Despite these benefits, the interpretability of AI-based systems or models remains vague. Attempts to address this issue had led to two novel explanation techniques, but none have shown enough robustness or comprehensiveness to be widely applied in AI and AMR control. A multidisciplinary collaboration between the medical field and advanced technology is therefore needed to partially manage this situation and improve the AI systems’ performance and their effectiveness against drug-resistant pathogens, in addition to multiple equity actions for mitigating the failure risks of AI due to a global-scale equity gap.Keywords: antibiotic, antimicrobial resistance, infection, artificial intelligence

Ngoc Quyen Nguyen,1 Trong Hau Phan2 1Department of Outpatient Clinic, 108 Military Central Hospital, Hanoi City, Vietnam; 2Department of Spinal Surgery, 108 Military Central Hospital, Hanoi City, VietnamCorrespondence: Ngoc Quyen Nguyen, Department of Outpatient Clinic, 108 Military Central Hospital, No. 1, Tran Hung Dao Street, Ha Ba Trung District, Hanoi, 113000, Vietnam, Tel +84-989052288, Email bsquyenptcs108@gmail.comBackground: The radiological complications including correction loss and hardware failure of short segment posterior pedicle screw fixation in the treatment of unstable thoracolumbar burst fractures remain a main concern. Several procedures aiming to reinforce the anterior column have been introduced to solve these limitations, including transforaminal interbody fusion (TIF). The purposes of this study were to evaluate the radiological complications of short-segment pedicle screw fixation in combination with transforaminal interbody fusion in the treatment of unstable thoracolumbar burst fractures.Methods: This retrospective case series study enrolled patients with isolated unstable thoracolumbar burst fractures, who were treated by posterior short fixation with TIF between January 2013 and January 2017. Patients were followed up for a minimum of one and half years. For evaluation of correction loss, % loss of anterior vertebral body height (%AVB), vertebral kyphotic angle (VA) and regional kyphotic angle (RA) were collected preoperatively, postoperatively and at the final follow-up. Hardware failure was assessed on radiological images at the last follow-up.Results: There were 36 patients who met the inclusion criteria with a mean follow-up duration of 53 months. The mean correction loss of %AVB, VA and RA were 10.2%, 2.9° and 5.6°, respectively. There were 6 patients (16.7%) with hardware failure at the final follow-up.Conclusion: Short-segment posterior pedicle screw fixation with TIF using bone chip grafts does not completely prevent hardware failure and progressive kyphosis in the treatment of unstable thoracolumbar burst fractures.Keywords: thoracolumbar burst fracture, short-segment fixation, transforaminal interbody fusion, hardware failure, correction loss

OBJECTIVES: : Delay in initiating enteral nutrition has been reported to disrupt intestinal mucosal integrity in animals and to prolong the duration of mechanical ventilation in humans. However, its impact on intestinal absorptive function in critically ill patients is unknown. The aim of this study was to examine the impact of delayed enteral nutrition on small intestinal absorption of 3-O-methyl-glucose. DESIGN: : Prospective, randomized study. SETTING: : Tertiary critical care unit. PATIENTS: : Studies were performed in 28 critically ill patients. INTERVENTIONS: : Patients were randomized to either enteral nutrition within 24 hrs of admission (14 'early feeding': 8 males, 6 females, age 54.9 ± 3.3 yrs) or no enteral nutrition during the first 4 days of admission (14 'delayed feeding': 10 males, 4 females, age 56.1 ± 4.2 yrs). MEASUREMENTS AND MAIN RESULTS: : Gastric emptying (scintigraphy, 100 mL of Ensure (Abbott Australia, Kurnell, Australia) with 20 MBq Tc-suphur colloid), intestinal absorption of glucose (3 g of 3-O-methyl-glucose), and clinical outcomes were assessed 4 days after intensive care unit admission. Although there was no difference in gastric emptying, plasma 3-O-methyl-glucose concentrations were less in the patients with delayed feeding compared to those who were fed earlier (peak: 0.24 ± 0.04 mmol/L vs. 0.37 ± 0.04 mmol/L, p < .02) and integrated (area under the curve at 240 mins: 38.5 ± 7.0 mmol/min/L vs. 63.4 ± 8.3 mmol/min/L, p < .04). There was an inverse correlation between integrated plasma concentrations of 3-O-methyl-glucose (area under the curve at 240 mins) and the duration of ventilation (r = -.51; p = .006). In the delayed feeding group, both the duration of mechanical ventilation (13.7 ± 1.9 days vs. 9.2 ± 0.9 days; p = .049) and length of stay in the intensive care unit (15.9 ± 1.9 days vs. 11.3 ± 0.8 days; p = .048) were greater. CONCLUSIONS: : In critical illness, delaying enteral feeding is associated with a reduction in small intestinal glucose absorption, consistent with the reduction in mucosal integrity after nutrient deprivation evident in animal models. The duration of both mechanical ventilation and length of stay in the intensive care unit are prolonged. These observations support recommendations for 'early' enteral nutrition in critically ill patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Enteral nutrient (EN) deprivation slows gastric emptying (GE) and increases plasma cholecystokinin (CCK) concentrations in healthy humans and may potentially contribute to the delayed GE in the critically ill. This study examined the impact of delayed feeding on GE, plasma CCK, and peptide YY (PYY) concentrations in the critically ill. DESIGN: Randomized controlled trial. SETTING: Mixed medical and surgical intensive care unit (ICU). INTERVENTIONS: Twenty-eight critically ill patients were randomized to receive EN either within 24 hrs of admission ('early feeding': 54.9 +/- 3.3 yrs; Acute Physiology and Chronic Health Evaluation (APACHE) II = 23.0 +/- 1.8) or on day 4 of admission after GE assessment ('delayed feeding': 56.1 +/- 4.2 yrs, APACHE II = 21.7 +/- 1.8). GE of 100 ml of Ensure was measured using scintigraphy on day 4 of admission. Blood was sampled for measurement of plasma CCK, PYY, and glucose concentrations. RESULTS: Demographics, APACHE II score, use of inotrope and morphine sedation were similar between the groups. The mean administered/prescribed caloric ratio in the 'early feeding' group was 72 +/- 4%. There were no differences in the retention of meal, intragastric meal distribution, proportion of patients with delayed GE (9/14 vs. 9/14), and plasma CCK and PYY concentrations during fasting and postprandially between the two groups. There was no relationship between the number of calories received and percentage of meal retention at 240 min (p > .05). However, delayed feeding was associated with longer duration of mechanical ventilations (13.7 +/- 1.9 vs. 9.2 +/- .9 days, p = .049) and length of stay in ICU (15.9 +/- 1.9 vs. 11.3 +/- 0.8 days, p = .048), but no difference in mortality. CONCLUSIONS: In critical illness, delayed enteral feeding appears to have little impact on either GE or the enterogastric feedback hormones. However, the association between delayed feeding and increased duration of ventilation and length of stay in the ICU supports the current recommendation that enteral nutrition should be commenced early. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the efficacy of combination therapy, with erythromycin and metoclopramide, to erythromycin alone in the treatment of feed intolerance in critically ill patients. DESIGN: Randomized, controlled, double-blind trial. SETTING: Mixed medical and surgical intensive care unit. PATIENTS: Seventy-five mechanically ventilated, medical patients with feed intolerance (gastric residual volume > or =250 mL). INTERVENTIONS: Patients received either combination therapy (n = 37; 200 mg of intravenous erythromycin twice daily + 10 mg of intravenous metoclopramide four times daily) or erythromycin alone (n = 38; 200 mg of intravenous erythromycin twice daily) in a prospective, randomized fashion. Gastric feeding was re-commenced and 6-hourly gastric aspirates performed. Patients were studied for 7 days. Successful feeding was defined as a gastric residual volume <250 mL with the feeding rate > or =40 mL/hr, over 7 days. Secondary outcomes included daily caloric intake, vomiting, postpyloric feeding, length of stay, and mortality. MEASUREMENTS AND MAIN RESULTS: Demographic data; use of inotropes, opioids, or benzodiazepines; and pretreatment gastric residual volume were similar between the two groups. The gastric residual volume was significantly lower after 24 hrs of treatment with combination therapy, compared with erythromycin alone (136 +/- 23 mL vs. 293 +/- 45 mL, p = .04). Over the 7 days, patients treated with combination therapy had greater feeding success, received more daily calories, and had a lower requirement for postpyloric feeding, compared with erythromycin alone. Tachyphylaxis occurred in both groups but was less with combination therapy. Sedation, higher pretreatment gastric residual volume, and hypoalbuminemia were significantly associated with a poor response. There was no difference in the length of hospital stay or mortality rate between the groups. Watery diarrhea was more common with combination therapy (20 of 37 vs. 10 of 38, p = .01) but was not associated with enteric infections, including Clostridium difficile. CONCLUSIONS: In critically ill patients with feed intolerance, combination therapy with erythromycin and metoclopramide is more effective than erythromycin alone in improving the delivery of nasogastric nutrition and should be considered as the first-line treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to a) compare the efficacy of metoclopramide and erythromycin in the treatment of feed intolerance in critical illness; and b) determine the effectiveness of 'rescue' combination therapy in patients who fail monotherapy. DESIGN: Randomized controlled trial. SETTING: Level III mixed medical and surgical intensive care unit. PATIENTS: Ninety mechanically ventilated, medical patients with feed-intolerance (gastric residual volume>or=250 mL). INTERVENTIONS: Patients received either metoclopramide 10 mg intravenously four times daily (n=45) or erythromycin 200 mg intravenously twice a day (n=45) in a double-blind, randomized fashion. After the first dose, nasogastric feeding was commenced and 6-hourly nasogastric aspirates were performed. If a gastric residual volume>or=250 mL recurred on treatment, open-label, combination therapy was given. Patients were studied for 7 days. Successful feeding was defined as 6-hourly gastric residual volume<250 mL with a feeding rate>or=40 mL/hr. MEASUREMENTS AND MAIN RESULTS: Demographic data, blood glucose levels, and use of inotropes, opioids, and benzodiazepines were similar between the two groups. After 24 hrs of treatment, both monotherapies reduced the mean gastric residual volume (metoclopramide, 830+/-32 mL to 435+/-30 mL, p<.0001; erythromycin, 798+/-33 mL to 201+/-19 mL, p<.0001) and improved the proportion of patients with successful feeding (metoclopramide=62% and erythromycin=87%). Treatment with erythromycin was more effective than metoclopramide, but the effectiveness of both treatments declined rapidly over time. In patients who failed monotherapy, rescue combination therapy was highly effective (day 1=92%) and maintained its effectiveness for the study duration (day 6=67%). High pretreatment gastric residual volume was associated with poor response to prokinetic therapy. CONCLUSIONS: In critical illness, erythromycin is more effective than metoclopramide in treating feed intolerance, but the rapid decline in effectiveness renders both treatments suboptimal. Rescue combination therapy is highly effective, and further study is required to examine its role as the first-line therapy. [ABSTRACT FROM AUTHOR]

Objective: Delayed gastric emptying and intolerance to gastric feeding occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Cholecystokinin (CCK) slows gastric emptying. The aim of this study was to determine plasma CCK concentrations during fasting and in response to small-intestine nutrient infusion in critically ill patients.Design: Randomized, controlled trial.Setting: Level 3, mixed medical and surgical intensive care unit.Subjects: A total of 31 mechanically ventilated, critically ill patients (23 men, 51 +/- 3 yrs) and 28 healthy subjects (21 men, 43 +/- 2 yrs).Interventions: Subjects received two 60-min duodenal infusions of Ensure (complete balanced nutrition), at 1 and 2 kcal/min, in a randomized, single-blind fashion. The nutrient infusions were separated by a 2-hr "washout" period. Blood samples for measurement of plasma CCK concentrations were obtained immediately before and every 20 mins during nutrient infusion.Measurements and Main Results: Baseline and nutrient-stimulated plasma CCK concentrations were higher in critically ill patients compared with healthy subjects (p < .001). The magnitude of the rise in plasma CCK in response to nutrients was also greater in the critically ill (p < .01). Of the 23 patients who received enteral nutrition before the study, nine were intolerant of gastric feeding. In these patients, both the baseline plasma CCK concentration and the magnitude of CCK increase during nutrient infusions were greater than in patients with feed tolerance (p < .002). Impaired renal function was associated with an increased baseline CCK concentration but had no effect on the CCK response to nutrients.Conclusions: Both fasting and nutrient-stimulated plasma CCK concentrations are increased in critically ill patients, particularly in those with feed intolerance. This may provide a humoral mechanism for delayed gastric emptying seen in critical illness. [ABSTRACT FROM AUTHOR]

Background: Poor intra-tumoural vascularity contributes to a lack of response to chemotherapy in pancreatic cancers. Preliminary data suggest that the addition of endoscopic ultrasound (EUS)-guided intra-tumoural injection of phosphorus-32 ( 32 P) microparticles to standard chemotherapy is potentially beneficial in locally advanced pancreatic cancer (LAPC). We aimed to assess changes in pancreatic tumour vascularity following 32 P implantation, using contrast-enhanced EUS (CE-EUS)., Methods: This was a prospective single-centre trial from January 2022 to 2024 of patients with unresectable, non-metastatic LAPC undergoing standard FOLFIRINOX chemotherapy and 32 P implantation. We performed CE-EUS pre-implantation after two chemotherapy cycles and 4 and 12 weeks after implantation. Time-intensity curves were analysed for 90 s after IV contrast bolus to ascertain peak intensity and intensity gain., Results: A total of 20 patients underwent 32 P implantation, with 15 completing 12-week follow-up. The technical success of 32 P implantation was 100%. The median primary tumour size reduced from 32 mm (IQR 27.5-38.75) pre-implantation to 24 mm (IQR 16-26) 12 weeks post-implantation ( p < 0.001). Five patients (25%) had tumour downstaging, and four underwent resections. The baseline (pre-implantation, post-chemotherapy) median intensity gain of contrast enhancement within the tumour was 32.15 (IQR 18.08-54.35). This increased to 46.85 (IQR 35.05-76.6; p = 0.007) and 66.3 (IQR 54.7-76.3; p = 0.001) at 4 weeks and 12 weeks post-implantation, respectively. Over a median follow-up of 11.2 months (IQR 7.8-12.8), 15/20 (75%) of patients remained alive, with 3/20 (15%) demonstrating local disease progression. Overall survival was not significantly different between patients with or without an increased intensity of 10 a.u. or more at 12 weeks post-implantation., Conclusion: This is the first clinical study to demonstrate treatment-induced increased vascularity within pancreatic primary tumours, which followed 32 P implantation and FOLFIRINOX chemotherapy. Larger comparative trials are warranted.

In recent years, the use of Building Information Modeling (BIM) with Building Energy Modeling (BEM) has become the primary research focus for reducing the energy consumption of buildings in the planning and operational phases. The combination of BIM and BEM offers advantages for the various phases of a construction project. However, there are currently very few studies that can integrate multi-objective optimization algorithms into the BIM-BEM process to achieve automatic optimization and effectively manage many aspects of building development. In this study, an EnergyPlus integrated multi-objective jellyfish search (EP-MOJSO) system was developed, utilizing an optimization algorithm to find the best thermal insulation layers for an Aluminum composite material (ACM) wall. The goal is to reduce the energy consumption and total cost in a BIM-BEM environment. In the case study, the authors successfully applied the system to a real building, resulting in a 10.7% reduction in total cost and a 65 kWh/m 2 /year reduction in EUI. It is expected that the results of the study will open up new ways of using algorithms for multi-criteria optimization in BIM models to optimize various project factors such as energy and total cost and thus make an important contribution to sustainable building design., (© 2024. The Author(s).)

With age, hematopoietic stem cells can acquire somatic mutations in leukemogenic genes that confer a proliferative advantage in a phenomenon termed "clonal hematopoiesis of indeterminate potential" (CHIP). How these mutations confer a proliferative advantage and result in increased risk for numerous age-related diseases remains poorly understood. We conducted a multiracial meta-analysis of epigenome-wide association studies (EWAS) of CHIP and its subtypes in four cohorts (N=8196) to elucidate the molecular mechanisms underlying CHIP and illuminate how these changes influence cardiovascular disease risk. The EWAS findings were functionally validated using human hematopoietic stem cell (HSC) models of CHIP. A total of 9615 CpGs were associated with any CHIP, 5990 with DNMT3A CHIP, 5633 with TET2 CHIP, and 6078 with ASXL1 CHIP (P <1×10 -7 ). CpGs associated with CHIP subtypes overlapped moderately, and the genome-wide DNA methylation directions of effect were opposite for TET2 and DNMT3A CHIP, consistent with their opposing effects on global DNA methylation. There was high directional concordance between the CpGs shared from the meta-EWAS and human edited CHIP HSCs. Expression quantitative trait methylation analysis further identified transcriptomic changes associated with CHIP-associated CpGs. Causal inference analyses revealed 261 CHIP-associated CpGs associated with cardiovascular traits and all-cause mortality (FDR adjusted p-value <0.05). Taken together, our study sheds light on the epigenetic changes impacted by CHIP and their associations with age-related disease outcomes. The novel genes and pathways linked to the epigenetic features of CHIP may serve as therapeutic targets for preventing or treating CHIP-mediated diseases., Competing Interests: Competing interests F.P. is an employee of Biomodal. L.M.R serves as a consultant for the NHLBI TOPMed Administrative Coordinating Center (through Westat). P.N. reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech / Roche, and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech / Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis, scientific advisory board membership of Esperion Therapeutics, Preciseli, TenSixteen Bio, and Tourmaline Bio, scientific co-founder of TenSixteen Bio, equity in MyOme, Preciseli, and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. No other authors have competing interests. The Jimma University Internal Review Board approved the study ensuring all procedures involving human participation adhere to ethical guidelines established by both the Institution and National Research Committee before any research began.

Motivation: Molecular core structures and R-groups are essential concepts in drug development. Integration of these concepts with conventional graph pre-training approaches can promote deeper understanding in molecules. We propose MolPLA, a novel pre-training framework that employs masked graph contrastive learning in understanding the underlying decomposable parts in molecules that implicate their core structure and peripheral R-groups. Furthermore, we formulate an additional framework that grants MolPLA the ability to help chemists find replaceable R-groups in lead optimization scenarios., Results: Experimental results on molecular property prediction show that MolPLA exhibits predictability comparable to current state-of-the-art models. Qualitative analysis implicate that MolPLA is capable of distinguishing core and R-group sub-structures, identifying decomposable regions in molecules and contributing to lead optimization scenarios by rationally suggesting R-group replacements given various query core templates., Availability and Implementation: The code implementation for MolPLA and its pre-trained model checkpoint is available at https://github.com/dmis-lab/MolPLA., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes., Methods: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up., Results: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up., Discussion: Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets., (Copyright © 2024 by The American College of Gastroenterology.)