Key risk factors and adverse outcomes in metachronous vertebral osteomyelitis following periprosthetic joint infection: A 5-year retrospective study.

Purpose: Periprosthetic joint infection (PJI) is a leading cause of joint arthroplasty failure, potentially leading to critical complications like vertebral osteomyelitis (VO). The factors contributing to VO after PJI and the outcomes for these patients are not well understood. Our study aims to (1) identify risk factors for VO following PJI and (2) assess the clinical outcomes in these cases. Methods: We included PJI patients treated surgically at our centre from January 2006 to December 2020, excluding those with simultaneous VO post-PJI. Our focus was on patients with VO occurring after PJI, monitored for at least 5 years. Analysis included patient comorbidities, PJI treatment approaches, pathogen identification and clinical outcomes. Results: Of 1701 PJI cases, 21 (1.23%) developed VO. Key risk factors for VO post-PJI were identified: systemic inflammatory response syndrome, substance misuse, polymicrobial infection and undergoing at least three stages of resection arthroplasty (odds ratios: 1.86, 54.28, 52.33 and 31.88, respectively). Adverse outcomes were noted in VO patients, with recurrent VO in 6/21 and repeated PJIs in 18/21 cases. Conclusions: Patients with PJI, especially those with certain risk factors, have an increased likelihood of developing VO and encountering negative outcomes. The potential role of bacteremia in the development of VO after PJI needs further exploration. Level of Evidence: Level III.

Robust inference for causal mediation analysis of recurrent event data.

Recurrent events, including cardiovascular events, are commonly observed in biomedical studies. Understanding the effects of various treatments on recurrent events and investigating the underlying mediation mechanisms by which treatments may reduce the frequency of recurrent events are crucial tasks for researchers. Although causal inference methods for recurrent event data have been proposed, they cannot be used to assess mediation. This study proposed a novel methodology of causal mediation analysis that accommodates recurrent outcomes of interest in a given individual. A formal definition of causal estimands (direct and indirect effects) within a counterfactual framework is given, and empirical expressions for these effects are identified. To estimate these effects, a semiparametric estimator with triple robustness against model misspecification was developed. The proposed methodology was demonstrated in a real-world application. The method was applied to measure the effects of two diabetes drugs on the recurrence of cardiovascular disease and to examine the mediating role of kidney function in this process.

Sodium-Glucose Cotransporter 2 Inhibitors Reduce the Risk of Hospitalization for Heart Failure and Amputation Rate Compared With Incretin-Based Therapy in Patients With Diabetic Foot Disease: A Nationwide Population-Based Study.

OBJECTIVE: Major adverse cardiovascular event (MACE) outcomes associated with sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapies remain unclear in patients with type 2 diabetes and newly diagnosed diabetic foot complications (DFCs). This study examined the impact of SGLT2i and GLP-1 RA use on the rates of MACEs and amputations in patients with type 2 diabetes and without cardiovascular disease. METHODS: Data from the Taiwan National Health Insurance Research Database (2004-2017) were analyzed, focusing on patients with type 2 diabetes without previous MACE and newly diagnosed DFCs. The primary outcome was the first MACE occurrence, and the secondary outcomes included MACE components, all-cause mortality, and lower extremity amputation (LEA) rates. RESULTS: SGLT2i users showed a significant decrease in the MACE (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.46-0.88) and hospitalization for heart failure (HR, 0.54; 95% CI, 0.35-0.83) rates compared with dipeptidyl peptidase-4 inhibitor users. The amputation rates were also lower in SGLT2i users without LEA at the first DFC diagnosis (HR, 0.28; 95% CI, 0.10-0.75) and did not increase in those with a history of peripheral artery disease or LEA. No significant differences were observed between dipeptidyl peptidase-4 inhibitor and GLP-1 RA users in terms of the primary or secondary outcomes. CONCLUSION: In patients with type 2 diabetes initially diagnosed with DFC, SGLT2i are effective in significantly reducing the hospitalization for heart failure and MACE rates. SGLT2i lower the amputation rates, especially in patients who have not previously had a LEA, than the dipeptidyl peptidase-4 inhibitor therapy.

Presentations of Children with Suspected Sepsis Caused by Acute Infectious Diarrhea in the Pediatric Emergency Department.

BACKGROUND: Acute infectious diarrhea is a common cause of hospitalization in children. Hence, early identification of acute bacterial gastroenteritis with suspected sepsis in pediatric emergency departments (EDs) is important. This study aimed to describe the clinical spectrum and initial characteristics of children who were presented to a pediatric ED with acute infectious diarrhea and suspected sepsis. METHODS: Between April 2020 to March 2021, children with clinical diagnoses of acute bacterial colitis and suspected sepsis who were admitted to the pediatric ED were prospectively enrolled. The following data were obtained and compared between different age groups of children: including demographics, presentation, laboratory tests, culture results, treatment modalities, complications, and short-term outcomes. RESULTS: A total of 105 patients (70 males and 35 females; mean age: 3.75 ± 3.52 years) were enrolled in this study. Of them, 89 (84.8%) patients were <6 years of age, and 80 (76.2%) patients required hospitalization for a duration of 4.7 ± 2.08 days. C-reactive protein (CRP) and procalcitonin (PCT) levels were significantly higher in the admission (both p < 0.001) and anti-biotic treatment groups (both p < 0.001). Salmonella enteritidis was the most common organism cultured from the stool and blood samples (39 of 91 (38.5%) and 2 of 105 (1.9%), respectively). CONCLUSIONS: The primary causative organism of acute infectious diarrhea identified in this study was S. enteritidis. Age and elevated serum CRP or PCT levels could be important factors in the decisions of emergency physicians regarding hospitalization and antibiotic therapies for pediatric acute infectious diarrhea.

Risk Factors for Urinary Tract Infections in Children with Hematuria in the Emergency Department.

INTRODUCTION: Hematuria is a worrisome symptom in children and is sometimes associated with urinary tract infections (UTIs). This study aimed to identify useful clinical factors that can predict UTIs in hematuria patients without pyuria in the pediatric emergency department (ED). METHODS: We retrospectively recruited patients with hematuria from the pediatric ED. Clinical symptoms, urine biochemistry and microscopic examination results, and blood laboratory tests were analyzed to identify the predictors of UTIs. Patients were divided into the verbal group (age ≥ 2 years) and non-verbal group (age < 2 years) for identifying predictors of UTIs. Causes of hematuria were also investigated. RESULTS: A total of 161 patients with hematuria without pyuria were evaluated. Among symptoms, dysuria was significantly correlated with UTIs. Regarding urine biochemistry data, urine esterase and urine protein > 30 mg/dl were found to be significant parameters for predicting UTIs, while urine esterase and urine nitrite showed significant differences in children with age < 2 years. In the urine microscopic examinations, urine red blood cells (RBC) > 373/µL in children aged ≥ 2 years and urine RBC > 8/µL in children aged < 2 years were associated with UTIs. In addition, UTIs and urinary tract stones were found to be the top two causes of hematuria. CONCLUSIONS: Dysuria, urine esterase, urine nitrite, and urine protein may be useful parameters for predicting UTIs in pediatric patients with hematuria but no pyuria in the ED. In addition, a UTI was the most commonly identified etiology of hematuria without pyuria, followed by urinary tract stones.

Efficacy evaluation of a bivalent subunit vaccine against classical swine fever virus and porcine circovirus type 2.

Classical swine fever virus (CSFV) and porcine circovirus type 2 (PCV2) are two of the most devastating and economically significant pathogens affecting pig populations worldwide. Administration of a combination of vaccines against swine pathogens has been demonstrated to be as efficacious as the administration of single vaccines. In this study, we developed and tested a novel bivalent subunit vaccine against CSFV and PCV2. The safety and efficacy of this vaccine were demonstrated in mice and specific pathogen-free (SPF) piglets. In addition to investigating the serological responses after immunization, challenge studies with both viruses were also conducted. The results showed that this CSFV/PCV2 bivalent vaccine elicited a high level of neutralizing antibodies against both viruses and provided protection in challenge studies. In conclusion, the CSFV/PCV2 bivalent vaccine is safe and effective against CSFV or PCV2 challenge.

Multiply robust estimation of natural indirect effects with multiple ordered mediators.

Multiple mediation analysis is a powerful methodology to assess causal effects in the presence of multiple mediators. Several methodologies, such as G-computation and inverse-probability-weighting, have been widely used to draw inferences about natural indirect effects (NIEs). However, a limitation of these methods is their potential for model misspecification. Although powerful semiparametric methods with high robustness and consistency have been developed for inferring average causal effects and for analyzing the effects of a single mediator, a comparably robust method for multiple mediation analysis is still lacking. Therefore, this theoretical study proposes a method of using multiply robust estimators of NIEs in the presence of multiple ordered mediators. We show that the proposed estimators not only enjoy the multiply robustness to model misspecification, they are also consistent and asymptotically normal under regular conditions. We also performed simulations for empirical comparisons of the finite-sample properties between our multiply robust estimators and existing methods. In an illustrative example, a dataset for liver disease patients in Taiwan is used to examine the mediating roles of liver damage and liver cancer in the pathway from hepatitis B/C virus infection to mortality. The model is implemented in the open-source R package "MedMR."

Efficacy of lidocaine wet compress combined with red-light irradiation for chronic wounds.

BACKGROUND: Chronic wounds that fail to progress through normal phases of healing present a significant healthcare burden owing to prolonged treatment and associated costs. Traditional wound care typically involves regular dressing changes, which can be painful. Recent approaches have explored the use of lidocaine to manage pain and red-light irradiation (RLI), known for its anti-inflammatory and cell proliferation effects, to potentially enhance wound healing. AIM: To investigate the therapeutic efficacy of lidocaine wet compression (LWC) combined with RLI for chronic wounds. METHODS: We enrolled 150 patients with chronic wounds from the Wound and Ostomy Outpatient Clinic of the Second Hospital of Anhui Medical University from April to September 2022. The wounds were treated with dressing changes. The patients were randomly assigned to the control and experimental groups using a random number table and given the same first dressing change (2% LWC for 5 min and routine dressing change). From the second dressing change, in addition to 2% LWC for 5 min and routine dressing change, the experimental group received RLI, whereas the control group continued to receive the same LWC and dressing change. The first and second dressing changes were performed on days 1 and 2, respectively. The third dressing change was performed 3 d after the second change. The frequency of subsequent dressing changes was determined based on wound exudation and pain. Pain during the first three dressing changes was evaluated in both groups. The average number of dressing changes within 28 d and the degree of wound healing on day 28 were also recorded. RESULTS: During the initial dressing change, no noticeable differences were observed in the pain levels experienced by the two groups, indicating similar pain tolerance. However, during the second and third dressing changes, the experimental group reported significantly less pain than the control group. Furthermore, over 28 d, the experimental group required fewer dressing changes than the control group. CONCLUSION: Notably, the effectiveness of wound healing on the 28th day was significantly higher in the experimental group than that of in the control group. The combination of LWC and RLI was effective in reducing early-stage pain, promoting wound healing, decreasing the frequency of dressing changes, and enhancing patients' overall quality of life with chronic wounds.

Obtaining organ-specific radiobiological parameters from clinical data for radiation therapy planning of head and neck cancers.

Objective.Different radiation therapy (RT) strategies, e.g. conventional fractionation RT (CFRT), hypofractionation RT (HFRT), stereotactic body RT (SBRT), adaptive RT, and re-irradiation are often used to treat head and neck (HN) cancers. Combining and/or comparing these strategies requires calculating biological effective dose (BED). The purpose of this study is to develop a practical process to estimate organ-specific radiobiologic model parameters that may be used for BED calculations in individualized RT planning for HN cancers.Approach.Clinical dose constraint data for CFRT, HFRT and SBRT for 5 organs at risk (OARs) namely spinal cord, brainstem, brachial plexus, optic pathway, and esophagus obtained from literature were analyzed. These clinical data correspond to a particular endpoint. The linear-quadratic (LQ) and linear-quadratic-linear (LQ-L) models were used to fit these clinical data and extract relevant model parameters (alpha/beta ratio, gamma/alpha,dTand BED) from the iso-effective curve. The dose constraints in terms of equivalent physical dose in 2 Gy-fraction (EQD2) were calculated using the obtained parameters.Main results.The LQ-L and LQ models fitted clinical data well from the CFRT to SBRT with the LQ-L representing a better fit for most of the OARs. The alpha/beta values for LQ-L (LQ) were found to be 2.72 (2.11) Gy, 0.55 (0.30) Gy, 2.82 (2.90) Gy, 6.57 (3.86) Gy, 5.38 (4.71) Gy, and the dose constraint EQD2 were 55.91 (54.90) Gy, 57.35 (56.79) Gy, 57.54 (56.35) Gy, 60.13 (59.72) Gy and 65.66 (64.50) Gy for spinal cord, optic pathway, brainstem, brachial plexus, and esophagus, respectively. Additional two LQ-L parametersdTwere 5.24 Gy, 5.09 Gy, 7.00 Gy, 5.23 Gy, and 6.16 Gy, and gamma/alpha were 7.91, 34.02, 8.67, 5.62 and 4.95.Significance.A practical process was developed to extract organ-specific radiobiological model parameters from clinical data. The obtained parameters can be used for biologically based radiation planning such as calculating dose constraints of different fractionation regimens.

Stem Cell Therapy in Children with Traumatic Brain Injury.

Pediatric traumatic brain injury is a cause of major mortality, and resultant neurological sequelae areassociated with long-term morbidity. Increasing studies have revealed stem cell therapy to be a potential new treatment. However, much work is still required to clarify the mechanism of action of effective stem cell therapy, type of stem cell therapy, optimal timing of therapy initiation, combination of cocurrent medical treatment and patient selection criteria. This paper will focus on stem cell therapy in children with traumatic brain injury.

Mesenchymal Stem Cells in the Treatment of COVID-19.

Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond the respiratory system, affecting various organs and functions. In severe cases, it can progress to acute respiratory distress syndrome (ARDS) and multi-organ failure, often fueled by an excessive immune response known as a cytokine storm. Mesenchymal stem cells (MSCs) have considerable potential because they can mitigate inflammation, modulate immune responses, and promote tissue regeneration. Accumulating evidence underscores the efficacy and safety of MSCs in treating severe COVID-19 and ARDS. Nonetheless, critical aspects, such as optimal routes of MSC administration, appropriate dosage, treatment intervals, management of extrapulmonary complications, and potential pediatric applications, warrant further exploration. These research avenues hold promise for enriching our understanding and refining the application of MSCs in confronting the multifaceted challenges posed by COVID-19.

Usability evaluation of augmented reality visualizations on an optical see-through head-mounted display for assisting machine operations.

This study explores the effect of using different visual information overlays and guiding arrows on a machine operation task with an optical see-through head-mounted display (OST-HMD). Thirty-four participants were recruited in the experiment. The independent variables included visual information mode (text, animation, and mixed text and animation) and the use of guiding arrows (with and without arrows). In addition, gender difference was also an objective of this study. The task performance indicators were determined based on task completion time and error counts as well as subjective measures (system usability scale, NASA task load index, and immersion scale). This study used the mixed analysis of variance design to evaluate the main and interaction effects. The results showed that males performed better when using the mixed text and animation mode. Females performed better when using the text mode. In addition, using the mixed text and animation mode demonstrated the best outcome in system usability scale and NASA task load index. For the use of guiding arrows, the task completion time was reduced and the system usability scale, NASA task load index, and immersion scale showed positive effects.

Combination of systemic immune-inflammation index and albumin-bilirubin grade predict prognosis of regorafenib in unresectable hepatocellular carcinoma.

Regorafenib improved prognosis for unresectable hepatocellular carcinoma (uHCC) after sorafenib treatment failure. We aimed to investigate prognostic value of combining systemic inflammatory markers with liver function evaluation in patients receiving sorafenib-regorafenib sequential therapy. A total of 122 uHCC patients who received sorafenib-regorafenib sequential therapy were retrospectively enrolled for analysis. The pre-treatment preserving liver function and six inflammatory indexes were collected. The Cox regression model was used to identify independent predictors of progression-free survival (PFS) and overall survival (OS). Baseline ALBI grade I (hazard ratio (HR) = 0.725, P = 0.040 for PFS; HR = 0.382, P = 0.012 for OS) and systemic inflammatory index (SII) ≤ 330 (HR = 0.341, P = 0.017 for OS; HR = 0.485, P = 0.037 for OS) were identified as independent prognostic factors in multivariable analysis and were used to develop the scoring system. Patients who fulfilled both criteria (2 points; score-high) had the longest median PFS (not-reached) and OS (not-reached), followed by fulfilling 1 criterion (1 point; score-intermediate; PFS: 3.7 months and OS: 17.9 months), and patients fulfilled no criterion (0 point; score-low; PFS: 2.9 months, overall log-rank P = 0.001 and OS: 7.5 months, overall log-rank P = 0.003). Additionally, best radiological response was significantly higher in patients with score-high (complete response/partial response/stable disease/progressive disease: score-high: 5.9%/5.9%/58.8%/29.4% vs. score-intermediate: 0%/14.0%/44.2%/41.9% vs. score-low: 0%/0%/25.0%/75.0%; P = 0.011). In conclusion, a combination of baseline ALBI grade and SII index can be used as a simple and powerful parameter to predict prognosis of uHCC patients receiving regorafenib after sorafenib-refractory treatment. The score may help with patient counseling but requires prospective validation.

Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A Comprehensive PENTEC Genitourinary Review.

PURPOSE: Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. METHODS AND MATERIALS: We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. RESULTS: The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and <3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a <5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. CONCLUSIONS: In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure.

Ketyl Radical Anion Mediated Radical Polymerization and Anionic Ring-Opening Polymerization to Give Polymers with Low Molecular Weight Distribution.

The development of novel polymerization capable of yielding polymers with low molecular weight distribution (D) is essential and significant in polymer chemistry, where monofunctional initiator contains only one initiation site in these polymerizations generally. Here, ketyl radical anion species is introduced to develop a novel Ketyl Mediated Polymerization (KMP), which enables radical polymerization at carbon radical site and anionic ring-opening polymerization at oxygen anion site, respectively. Meanwhile, polymerization and corresponding organic synthesis generally couldn't be performed simultaneously in one pot. Through KMP, organic synthesis and polymerization are achieved in one pot, where small molecules (cyclopentane derivates) and polymers with low D are successfully prepared under mild condition simultaneously. At the initiation step, both organic synthesis and polymerization are initiated by single electron transfer reaction with ketyl radical anion formation. Cyclopentane derivates are synthesized through 3-3 coupling reaction and cyclization. Polystyrene and polycaprolactone with low D and a full monomer conversion are prepared by KMP via radical polymerization and anionic ring-opening polymerization, respectively. This work therefore enables both organic synthesis and two different polymerizations from same initiation system, which saves time, labour, resource and energy and expands the reaction mode and method libraries of organic chemistry and polymer chemistry.

Current and emerging therapies for Achondroplasia: The dawn of precision medicine.

Achondroplasia is a rare disease affecting bone growth and is caused by a missense mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. In the past few years, there were multiple experimental drugs entering into clinical trials for treating achondroplasia including vosoritide, the first precision medicine approved for this indication. This perspective presents the mechanism of action, benefit, and potential mechanistic limitation of the drugs currently being evaluated in clinical trials for achondroplasia. This article also discusses the potential impact of those drugs not only in increasing the growth of individuals living with achondroplasia but also in improving their quality of life.

Synthesis and biological evaluation of biaryl alkyl ethers as inhibitors of IDO1.

Starting from the dialkylaniline indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor lead 3 (IDO1 HeLa IC50 = 7.0 nM), an iterative process of synthesis and screening led to cyclized analog 21 (IDO1 HeLa IC50 = 3.6 nM) which maintained the high potency of 3 while addressing issues of lipophilicity, cytochrome P450 (CYP) inhibition, hERG (human potassium ion channel Kv11.1) inhibition, Pregnane X Receptor (PXR) transactivation, and oxidative metabolic stability. An x-ray crystal structure of a biaryl alkyl ether 11 bound to IDO1 was obtained. Consistent with our earlier results, compound 11 was shown to bind to the apo form of the enzyme.

Real-time motion monitoring using orthogonal cine MRI during MR-guided adaptive radiation therapy for abdominal tumors on 1.5T MR-Linac.

BACKGROUND: Real-time motion monitoring (RTMM) is necessary for accurate motion management of intrafraction motions during radiation therapy (RT). PURPOSE: Building upon a previous study, this work develops and tests an improved RTMM technique based on real-time orthogonal cine magnetic resonance imaging (MRI) acquired during magnetic resonance-guided adaptive RT (MRgART) for abdominal tumors on MR-Linac. METHODS: A motion monitoring research package (MMRP) was developed and tested for RTMM based on template rigid registration between beam-on real-time orthogonal cine MRI and pre-beam daily reference 3D-MRI (baseline). The MRI data acquired under free-breathing during the routine MRgART on a 1.5T MR-Linac for 18 patients with abdominal malignancies of 8 liver, 4 adrenal glands (renal fossa), and 6 pancreas cases were used to evaluate the MMRP package. For each patient, a 3D mid-position image derived from an in-house daily 4D-MRI was used to define a target mask or a surrogate sub-region encompassing the target. Additionally, an exploratory case reviewed for an MRI dataset of a healthy volunteer acquired under both free-breathing and deep inspiration breath-hold (DIBH) was used to test how effectively the RTMM using the MMRP can address through-plane motion (TPM). For all cases, the 2D T2/T1-weighted cine MRIs were captured with a temporal resolution of 200 ms interleaved between coronal and sagittal orientations. Manually delineated contours on the cine frames were used as the ground-truth motion. Common visible vessels and segments of target boundaries in proximity to the target were used as anatomical landmarks for reproducible delineations on both the 3D and the cine MRI images. Standard deviation of the error (SDE) between the ground-truth and the measured target motion from the MMRP package were analyzed to evaluate the RTMM accuracy. The maximum target motion (MTM) was measured on the 4D-MRI for all cases during free-breathing. RESULTS: The mean (range) centroid motions for the 13 abdominal tumor cases were 7.69 (4.71-11.15), 1.73 (0.81-3.05), and 2.71 (1.45-3.93) mm with an overall accuracy of <2 mm in the superior-inferior (SI), the left-right (LR), and the anterior-posterior (AP) directions, respectively. The mean (range) of the MTM from the 4D-MRI was 7.38 (2-11) mm in the SI direction, smaller than the monitored motion of centroid, demonstrating the importance of the real-time motion capture. For the remaining patient cases, the ground-truth delineation was challenging under free-breathing due to the target deformation and the large TPM in the AP direction, the implant-induced image artifacts, and/or the suboptimal image plane selection. These cases were evaluated based on visual assessment. For the healthy volunteer, the TPM of the target was significant under free-breathing which degraded the RTMM accuracy. RTMM accuracy of <2 mm was achieved under DIBH, indicating DIBH is an effective method to address large TPM. CONCLUSIONS: We have successfully developed and tested the use of a template-based registration method for an accurate RTMM of abdominal targets during MRgART on a 1.5T MR-Linac without using injected contrast agents or radio-opaque implants. DIBH may be used to effectively reduce or eliminate TPM of abdominal targets during RTMM.