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Accounting for Competing Risks in Clinical Research

JAMA. 2024 May 29. doi: 10.1001/jama.2024.4970. Online ahead of print.

NO ABSTRACT

PMID:38809526 | DOI:10.1001/jama.2024.4970

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The efficacy of intravenous application of the Mycobacterium Cell Wall Fraction (AMPLIMUNE) in the treatment of subclinical mastitis caused by S. Aureus

Vet Res Commun. 2024 May 29. doi: 10.1007/s11259-024-10426-9. Online ahead of print.

ABSTRACT

The aim of the study was to investigate the effect of the immunostimulant Mycobacterium Cell Wall Fraction (MCWF) on the treatment of S. aureus SCM by intravenous application. The study included 45 HF dairy cows in 2nd and 3rd month after parturition divided into three groups (n = 15 per group): the MC + group – cows with S. aureus SCM treated with MCWF; the MC- group – cows with S. aureus SCM, with no treatment; and the C group – the control group of healthy cow with no treatment. Samples were collected 0th (I sample), 7th (II), and 14th day (III) from the day of SCM diagnosis and on day 21st (IV). A greater influx of leukocytes was confirmed into milk after 7 days after MCWF treatment in MC + group, which was followed by increase of WBC and LYM in blood. These results support the hypothesis of effective action of MCWF, and in quarters with lower-grade infection, bacteriological cure was achieved. The MC- group had a statistically higher concentration of TBARS and CAT activity in milk, while MC + group had lower blood serum LDH activity, which indicates a positive effect of the MCWF application and a lower exposure of the tissue to lipide peroxidation and inflammation caused by S. aureus. The application of MCWF would give new possibilities in the prevention and therapy of mammary gland diseases without fear of the presence of residues and the emergence of bacterial resistance. In future studies, the effects of local and systemic application of MCWF in the treatment of S. aureus SCM should be compared.

PMID:38809504 | DOI:10.1007/s11259-024-10426-9

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Diagnostic efficacy of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for early detection of acute kidney injury in dogs with leptospirosis or babesiosis

Vet Res Commun. 2024 May 29. doi: 10.1007/s11259-024-10416-x. Online ahead of print.

ABSTRACT

This study evaluates the diagnostic efficacy of urinary biomarkers, Neutrophil Gelatinase-Associated Lipocalin (uNGAL), and Kidney Injury Molecule-1 (uKIM-1), in identifying Acute Kidney Injury (AKI) in dogs affected with leptospirosis or babesiosis. Acute kidney injury was diagnosed based on the increase in serum creatinine levels above 0.3 mg/dL within 48 h and dogs were categorized according to AKI grades based on International Renal Interest Society guidelines. Traditional biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers like urinary NGAL and urinary KIM-1 levels were measured and compared to concentrations obtained in control dogs. Statistical analysis assessed significant differences (P < 0.01) across AKI grades, specifically noting elevated urinary NGAL and KIM-1 in IRIS grade I AKI (P < 0.001). The study highlights the diagnostic significance of urinary NGAL and KIM-1 as early indicators of renal damage, particularly valuable in non-azotemic AKI cases, offering promising markers for early AKI diagnosis in veterinary clinical settings. These biomarkers demonstrate clinical utility and underscore their potential for improving AKI management in veterinary medicine. Further validation studies involving larger cohorts and diverse etiologies of AKI are needed to confirm the diagnostic accuracy and clinical utility of urinary NGAL and KIM-1 in veterinary practice.

PMID:38809503 | DOI:10.1007/s11259-024-10416-x

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Prevalence and outcomes of fear of falling in older adults with falls at the emergency department: a multicentric observational study

Eur Geriatr Med. 2024 May 29. doi: 10.1007/s41999-024-00992-1. Online ahead of print.

ABSTRACT

PURPOSE: Fear of falling (FOF) may result in activity restriction and deconditioning. The aim of the study was to identify factors associated with FOF in older patients and to investigate if FOF influenced long-term outcomes.

METHODS: Multicentric, observational, prospective study including patients 65 years or older attending the emergency department (ED) after a fall. Demographical, patient- and fall-related features were recorded at the ED. FOF was assessed using a single question. The primary outcome was all-cause death. Secondary outcomes included new fall-related visit, fall-related hospitalisation, and admission to residential care. Logistic regression and Cox regression models were used for statistical analyses.

RESULTS: Overall, 1464 patients were included (47.1% with FOF), followed for a median of 6.2 years (2.2-7.9). Seven variables (age, female sex, living alone, previous falls, sedative medications, urinary incontinence, and intrinsic cause of the fall) were directly associated with FOF whereas use of walking aids and living in residential care were inversely associated. After the index episode, 748 patients (51%) died (median 3.2 years), 677 (46.2%) had a new fall-related ED visit (median 1.7 years), 251 (17.1%) were hospitalised (median 2.8 years), and 197 (19.4%) were admitted to care (median 2.1 years). FOF was associated with death (HR 1.239, 95% CI 1.073-1.431), hospitalisation (HR 1.407, 95% CI 1.097-1.806) and institutionalisation (HR 1.578, 95% CI 1.192-2.088), but significance was lost after adjustment.

CONCLUSION: FOF is a prevalent condition in older patients presenting to the ED after a fall. However, it was not associated with long-term outcomes. Future research is needed to understand the influence of FOF in maintenance of functional capacity or quality of life.

PMID:38809489 | DOI:10.1007/s41999-024-00992-1

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Modulated Arc Therapy for hippocampal-avoidance whole brain radiation therapy: planning comparison with intensity modulated Radiation Therapy

Radiat Environ Biophys. 2024 May 29. doi: 10.1007/s00411-024-01075-2. Online ahead of print.

ABSTRACT

This study aimed to evaluate the modulated arc therapy (mARC) technique as a planning and treatment option for hippocampal sparing whole brain radiotherapy (HS-WBRT) following the Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Computed tomography (CT) and magnetic resonance imaging (MRI) were selected retrospectively for 15 patients. Two types of plans were created for each patient, namely an intensity-modulated radiation therapy (IMRT) and a mARC plan. IMRT and mARC plans were compared in terms of plan quality indices, absorbed dose to organs at risk (OARs), number of monitor units (MUs), and treatment time. All plans in both techniques were considered clinically acceptable for treatment. However, IMRT plans presented a higher conformity (p = 0.01) as well as a higher homogeneity as compared to mARC plans, but this difference was not statistically significant (p > 0.05). In terms of the preservation of the hippocampus, it was observed that the IMRT plans achieved significantly lower doses for both 100% of its volume and for its maximum dose (p < 0.001). The evaluation of the remaining OARs showed that the IMRT technique resulted in lower doses, and significant differences were observed for the following organs: left cochlea (p < 0.001), left eye (p < 0.001), right eye (p = 0.03), both lenses of the eye (p < 0.001), and right optic nerve (p = 0.02). Despite these differences, the absolute differences in all dosimetric parameters were low enough to bear any clinical relevance. A drastic (close to 65%) and significant (p < 0.001) decrease was observed in the number of MUs for the mARC plans. This resulted in a substantial decrease in treatment time (60.45%, p < 0.001). It is concluded that the mARC technique is a feasible planning and treatment solution for HS-WBRT that meets the RTOG 0933 criteria. The main advantage of using mARC over IMRT for HS-WBRT is the considerable reduction in MUs and treatment time.

PMID:38809486 | DOI:10.1007/s00411-024-01075-2

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Distribution and predictors of F-18-FDG uptake values of non-malignant cervical lymph nodes in pediatric patients

EJNMMI Res. 2024 May 29;14(1):52. doi: 10.1186/s13550-024-01110-9.

ABSTRACT

BACKGROUND: F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes can be involved in some pediatric malignancies, but increased uptake in non-malignant cervical lymph nodes is not exceptional in this population. The aim of the present study is to identify predictors of the maximum uptake in non-malignant cervical lymph nodes in the pediatric population.

METHODS: 191 FDG PET/CT studies of pediatric patients without malignant involvement of cervical lymph nodes were retrospectively reviewed. The maximal Standard Uptake Value in the hottest cervical lymph node (SUVmaxCLN), as well as demographic, technical and imaging variables were recorded. The predictive effect of those variables on SUVmaxCLN was estimated using linear regression models.

RESULTS: Increased FDG activity in cervical nodes was observed in 136/191 studies (71%). The mean SUVmaxCLN was 2.2 ± 1.3. Ipsilateral palatine tonsil SUVmax, mean liver uptake, and treatment status were all statistically significant predictors of SUVmaxCLN. However, in multivariate regression analysis, only ipsilateral palatine tonsil SUVmax was found to be significant. In addition, SUVmaxCLN was greater than the mean liver uptake in 50% of all studies. This proportion was higher in younger children, reaching 77% of studies of children younger than six years.

CONCLUSION: SUVmax in ipsilateral palatine tonsil is a strong predictor of the maximal uptake value of non-malignant cervical lymph nodes in children. The intensity of uptake in non-malignant cervical lymph nodes is frequently higher than liver uptake in children, and this tendency increases for younger patients.

TRIAL WAS REGISTERED: In the internal hospital registry under TRN 0209-22-HMO on date 23.04.2022.

PMID:38809472 | DOI:10.1186/s13550-024-01110-9

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Perioperative efficacy of laparoscopic duodenal-preserving pancreatic head resection

Zhonghua Wai Ke Za Zhi. 2024 May 29;62(7):671-676. doi: 10.3760/cma.j.cn112139-20240317-00130. Online ahead of print.

ABSTRACT

Objective: To compare the perioperative outcomes of laparoscopic duodenal-preserving pancreatic head resection(LDPPHR) with laparoscopic pancreaticoduodenectomy(LPD) in the treatment of borderline and benign diseases of the pancreatic head. Methods: This is a retrospective cohort study. Perioperative data from 87 patients with non-malignant pancreatic head diseases who underwent LDPPHR or LPD were retrospectively collected in the Department of Biliary-Pancreatic Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2020 to December 2022. There were 49 male and 38 female patients with an age of 57.0(16.5) years (range: 20 to 75 years). Forty patients underwent LDPPHR and 47 patients underwent LPD. Quantitative data following a normal distribution were compared using Student’s t-test, while quantitative data not following a normal distribution were compared using the Mann-Whitney U test. Comparisons of categorical or ordinal variables were made using χ2 test or Fisher’s exact test. Logistic regression analysis was used to estimate the risk factors associated with the rate of complications. Results: There were no statistically significant differences between the LDPPHR group and the LPD group in terms of reoperation rate,total hospital stay duration,postoperative hospital stay duration,90-day mortality rate,30-day and 90-day readmission rates,and 2-year tumor recurrence rate (all P>0.05). The complication rate was higher in the LDPPHR group compared to the LPD group(32 cases (80.0%) vs. 24 cases (51.1%),χ2=7.89,P=0.005),but there was no difference in the rate of Clavien-Dindo classification of surgical complications≥Ⅲ between the two groups(4 cases (10.0%) vs. 6 cases (12.8%), χ2<0.01, P=0.947). Additionally,the rate of delayed gastric emptying (DGE) was higher in the LDPPHR group compared to the LPD group (χ2=10.79,P=0.001),but there was no statistically significant difference in the rate of B,C grade DGE between the two groups (χ2=0.48, P=0.487). There were no statistically significant differences in the rates of postoperative pancreatic fistula,bile leakage,post-pancreatectomy hemorrhage,intra-abdominal infection,and pulmonary infection between the two groups (all P>0.05). The results of the univariate logistic regression analysis showed that LDPPHR (compared to LPD, OR=3.83, 95%CI: 1.46 to 10.04, Z=2.73,P=0.006) and preoperative biliary stent placement (compared to non-use of biliary stent, OR=5.30, 95%CI: 1.13 to 25.00, Z=2.11, P=0.035) were risk factors for the complication rate,but neither was an independent risk factor for complication rate (all P>0.05). Conclusion: The preliminary results suggest that LDPPHR can achieve perioperative safety and effectiveness comparable to LPD.

PMID:38808434 | DOI:10.3760/cma.j.cn112139-20240317-00130

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Clinical effect of the modified pharyngeal flap of bilateral muscular rings in the treatment of moderate and severe velopharyngeal insufficiency

Zhonghua Kou Qiang Yi Xue Za Zhi. 2024 May 27;59(6):610-614. doi: 10.3760/cma.j.cn112144-20231031-00230. Online ahead of print.

ABSTRACT

To introduce the modified pharyngeal flap of bilateral muscular rings(BMR), and to discuss the clinical effect of this operation in the correction of moderate and severe velopharyngeal insufficiency. The clinical data of 18 patients who underwent BMR surgery in the Department of Craniofacial Plastic and Aesthetic Surgery, School of Stomatology, The Fourth Military Medical University from May 2019 to July 2021 were retrospectively analyzed. There were 10 males and 8 females, with a median age of 8.5 years (aged from 5 to 34 years). The patients were diagnosed preoperatively with moderate to severe velopharyngeal insufficiency (velopharyngeal closure ratio<0.7). The results of nasopharyngoscopy and speech assessment were compared and analyzed before operation and at the follow-up 6 months after the operation to evaluate the changes in velopharyngeal function and speech. Eighteen patients underwent BMR, 4 patients had snoring (the symptom disappeared after a few weeks in 3 cases), and 2 patients had local erosion of the wound, which delayed healing. Postoperative nasopharyngoscopy showed that all patients achieved comparatively complete velopharyngeal closure, some patients got enhanced lateral pharyngeal wall motility, and all patients got active motility of posterior pharyngeal wall flap. The postoperative speech assessment was significantly improved compared with that before the operation. The preoperative median score was 9 (range 7-12), and the postoperative median score was 2 (range 0-4). The statistical analysis was performed by paired non-parametric Wilcoxon signed rank test, and the difference was statistically significant (P<0.001). BMR is a reliable method for the treatment of moderate and severe velopharyngeal insufficiency. This technique can achieve functional contraction of the full circumference of the ventilator while preserving the obstructive effect of the posterior pharyngeal wall flap, which is helpful to balance nasal ventilation and velopharyngeal closure and improve the velopharyngeal function of patients.

PMID:38808422 | DOI:10.3760/cma.j.cn112144-20231031-00230

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Explorations about the correlation between biological changes of meninges in periodontitis mice and cognitive impairment via single-cell RNA sequencing

Zhonghua Kou Qiang Yi Xue Za Zhi. 2024 May 27;59(6):595-603. doi: 10.3760/cma.j.cn112144-20231102-00234. Online ahead of print.

ABSTRACT

Objective: To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing. Methods: Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of Atf3 and Apold1. Results: Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest (CEJ-ABC) in experimental mice [(185.60±17.60), (206.90±13.37) μm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) μm] (t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm; (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm; (3.05±0.93) cm/s] (t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] (t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests (t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) (t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) (t=3.88, P=0.005; t=3.02, P=0.017). Conclusions: The mice chronically infected with W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

PMID:38808420 | DOI:10.3760/cma.j.cn112144-20231102-00234

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A kinetic study of mechanically activated atom exchange: the effect of milling frequency and ball mass

Phys Chem Chem Phys. 2024 May 29. doi: 10.1039/d3cp06147g. Online ahead of print.

ABSTRACT

This study investigates the mechanochemical reaction of hydrogen isotope exchange between solid benzoic acid and liquid heavy water. The systematic change of milling conditions revealed that the reaction rate scales with the milling frequency and the mass of the milling balls. The ball size being always the same, faster reactions stem from the use of higher milling frequencies and heavier balls. The kinetic curves are described by a kinetic model that accounts for the statistical, deformational and chemical factors involved in mechanochemical transformations. The results indicate that the reaction is driven by the generation of a new interface area caused by the deformation of the solid reactants.

PMID:38808410 | DOI:10.1039/d3cp06147g