Nevin Manimala

Med Eng Phys. 2023 Sep;119:104027. doi: 10.1016/j.medengphy.2023.104027. Epub 2023 Jul 20.

ABSTRACT

Early aseptic loosening following primary total knee arthroplasty related to several factors might appear at the interface implant-cement or cement-bone. A standardized in vitro model might provide information on the relevance of single variable parameter of cementation including technique and cement respectively bone structure on fixation strength. Micromotion measurement using different directions of load should detect the primary stability of the interfaces. An open-cell rigid foam model was used for cementation of PFC-Sigma tibial trays with Palacos®. Pins were applied to the model for continuous non-destructive measurement. Relative micromotions for rotation, valgus-varus and extension flexion stress were detected at the interfaces as well as cement penetration was measured. The reproducibility of the measurement could be shown for all interfaces in extension-flexion movements. For rotation a negative trend was shown for the interface cement-prosthesis and cement-bone concerning varus-valgus stress reflecting varying surgical cementation technique. More micromotion related to extension-flexion force might reflect the design of the implant. Measurement of relative micromotion and cement distribution appear accurate to detect small differences of movement at different interfaces of cemented tibial implants and the results are reproducible for most parameter. An increased number of specimens should achieve statistical relevance for all measurements.

PMID:37634907 | DOI:10.1016/j.medengphy.2023.104027

Med Eng Phys. 2023 Sep;119:104025. doi: 10.1016/j.medengphy.2023.104025. Epub 2023 Jul 22.

ABSTRACT

Deep inferior epigastric artery perforator (DIEAP) flap reconstruction surgeries can potentially benefit from augmented reality (AR) in the context of surgery planning and outcomes improvement. Although three-dimensional (3D) models help visualize and map the perforators, the anchorage of the models to the patient’s body during surgery does not consider eventual skin deformation from the moment of computed tomography angiography (CTA) data acquisition until the position of the patient while in surgery. In this work, we compared the 3D deformation registration from supine arms down (CTA position) to supine with arms at 90° degrees (surgical position), estimating the patient’s skin deformation. We processed the data sets of 20 volunteers with a 3D rigid registration tool and performed a descriptive statistical analysis and statistical inference. With 2.45 mm of root mean square and 2.89 mm of standard deviation, results include 30% cases of deformation above 3 mm and 15% above 4 mm. Pose transformation deformation indicates that 3D surface data from the CTA scan position differs from data acquired in loco at the surgical table. Such results indicate that research should be conducted to construct accurate 3D models using CTA data to display on the patient, while considering projection errors when using AR technology.

PMID:37634903 | DOI:10.1016/j.medengphy.2023.104025

Open Heart. 2023 Aug;10(2):e002313. doi: 10.1136/openhrt-2023-002313.

ABSTRACT

AIM: To create and validate a simple scoring system for predicting 30-day mortality in patients presenting with acute coronary syndromes (ACS) at their moment of admission.

METHODS AND RESULTS: 2407 consecutive patients presenting to Harefield Hospital with measured arterial blood gases, from January 2011 to December 2020, were studied to build the training set. 30-day mortality in this group was 17.2%. A scoring algorithm that was built using binary logistic regression of variables available on admission was then converted to an additive risk score. The resultant scoring system is the BE-ALIVE score, which incorporates the following factors:Base Excess (1 point for <-2 mmol/L), Age (<65 years: 0 points, 65-74: 1 point, 75-84: 2 points, ≥85: 3 points), Lactate (<2 mmol/L: 0 points, 2-4.9: 1 point, 5-9.9: 3 points, ≥10: 6 points), Intubated (2 points), Left Ventricular function (mildly impaired or better: -1 point, moderately impaired: 1 point, severely impaired: 3 points) and External/out of hospital cardiac arrest 2 points).The scoring system was validated using a testing set of 515 patients presenting to Harefield Hospital in 2021. The validation metrics were excellent with a c-statistic of 0.9, Brier’s score 0.06 vs a naïve classifier of 0.15, Spiegelhalter’s z-statistic probability of 0.267 and a calibration slope of 1.08.

CONCLUSION: The BE-ALIVE score is a simple and accurate scoring system to predict 30-day mortality in patients presenting with ACS. Appreciating this mortality risk can allow prompt involvement of appropriate care such as the shock team.

PMID:37634901 | DOI:10.1136/openhrt-2023-002313

Clin Respir J. 2023 Aug 27. doi: 10.1111/crj.13674. Online ahead of print.

ABSTRACT

BACKGROUND: The clinical indications of extracorporeal membrane oxygenation (ECMO) in immunosuppressed patients are not clear. This study aimed to analyse the effectiveness of ECMO and to identify the risk factors for the mortality of ECMO in immunocompromised patients with acute respiratory failure.

METHODS: This retrospective, cohort study included 46 confirmed immunocompromised patients with acute hypoxemic respiratory failure treated with ECMO between July 2014 and August 2020. The clinical features and outcomes of the survival group and the non-survival group were statistically analysed.

RESULTS: The mean age of the enrolled patients was 60.0 (50.0, 66.0) years; male patients accounted for 60.9% of patients, and the mean CD4 level was 213 cells/μL (150.3, 325.3). The hospital mortality rate of the cohort was 67.4% (31/46 patients). Patients in the survival group showed a higher rate of receiving awake ECMO (11/15 vs. 4/31; p = 0.006), a lower rate of acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT) (1/15 vs. 12/31; p = 0.035), fewer platelet transfusion units (0/15 vs. 2/31 units; p = 0.039) and a lower rate of ventilator-associated pneumonia (2/15 vs. 19/31; p = 0.006). In a multivariate Cox regression analysis model, intubated ECMO (hazard ratio = 1.77, 95% confidence interval: 1.34-2.32, p < 0.001) and AKI requiring CRRT (1.37, 95% confidence interval: 1.14-1.61, p = 0.003) were identified as independent risk factors for mortality.

CONCLUSIONS: In-hospital mortality has remained high in ECMO-treated immunocompromised patients with acute respiratory failure. Intubated ECMO and AKI receiving CRRT during ECMO treatment may predict ECMO failure in immunocompromised patients with ARF. A primarily awake ECMO strategy seems feasible in some selected immunocompromised patients.

PMID:37634899 | DOI:10.1111/crj.13674

Fam Process. 2023 Aug 27. doi: 10.1111/famp.12930. Online ahead of print.

ABSTRACT

Community-based family-focused interventions can offer support to families of children with chronic health conditions. This review aimed to evaluate the effectiveness of community-based family-focused interventions in improving family functioning, disease knowledge, and child health outcomes among families of children with chronic health conditions. Eight electronic databases (MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO, Scopus, Web of Science, and ProQuest Dissertations & Theses Global) and one trial registry (ClinicalTrials.gov) were searched from their dates of inception to October 2022. Meta-analysis was performed under the random-effect model when appropriate otherwise, findings were narratively synthesized. I² statistics and Cochran’s Q chi-squared test were used to determine heterogeneity. Quality appraisal was conducted by the Cochrane risk of bias tool and the Grades of Recommendation, Assessment, Development, and Evaluation approach at the study and outcome level, respectively. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guided this review. Eight studies were included in this review. Community-based family-focused interventions were viable methods that could support families of children with chronic health conditions. Family-focused interventions that incorporate guided role-playing exercises for parents and children, psychoeducational components, and elements from relationship-focused interventions could support families more effectively. However, current findings are mostly limited to interventions conducted in patients’ homes, and the long-term effect of these interventions cannot be determined. Overall, community-based family-focused interventions have the potential to offer valuable support to families of children with chronic health conditions, and future research could seek to improve the effectiveness of these interventions.

PMID:37634898 | DOI:10.1111/famp.12930

J Korean Neurosurg Soc. 2023 Aug 25. doi: 10.3340/jkns.2023.0157. Online ahead of print.

ABSTRACT

OBJECTIVE: Subarachnoid hemorrhage (SAH) is a condition characterized by bleeding in the subarachnoid space, often resulting from the rupture of a cerebral aneurysm. Delayed cerebral ischemia (DCI) caused by vasospasm is a significant cause of mortality and morbidity in SAH patients, and inflammatory markers such as systemic inflammatory response index (SIRI), systemic inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), and derived NLR (dNLR) have shown potential in predicting clinical vasospasm and outcomes in SAH patients. This article aims to investigate the relationship between inflammatory markers and cerebral vasospasm after aneurysmatic subarachnoid hemorrhage (aSAH) and evaluate the predictive value of various indices, including systemic inflammatory response index (SIRI), systemic inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), and derived NLR (dNLR), in predicting clinical vasospasm.

METHODS: A retrospective analysis was performed on a cohort of 96 patients who met the inclusion criteria out of a total of 139 patients admitted XXXXXXXXXXX hospital with a confirmed diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) between January 2013 and December 2021. Diagnostic procedures, neurological examinations, and laboratory tests were performed to assess the patients’ condition. The Student’s t-test compared age variables, while the chi-square test compared categorical variables between the non-vasospasm (NVS) and vasospasm (VS) groups. Receiver operating characteristic (ROC) curve analyses were used to evaluate the diagnostic accuracy of laboratory parameters, calculating the area under the ROC curve (AUC), cut-off values, sensitivity, and specificity. A significance level of p < 0.05 was considered statistically significant.

RESULTS: The study included 96 patients divided into two groups: NVS (non-vasospasm) and VS (vasospasm). Various laboratory parameters, such as NLR, SII, and dNLR, were measured daily for 15 days, and statistically significant differences were found in NLR on seven days, with specific cut-off values identified for each day. SII showed a significant difference on day 9, while dNLR had significant differences on days 2, 4, and 9. Graphs depicting the values of these markers for each day are provided.

CONCLUSION: Neuroinflammatory biomarkers, when used alongside radiology and scoring scales, can aid in predicting prognosis, determining severity and treatment decisions for aneurysmal subarachnoid hemorrhage (aSAH), and further studies with larger patient groups are needed to gain more insights.

PMID:37634893 | DOI:10.3340/jkns.2023.0157

Neuroimage. 2023 Aug 25:120346. doi: 10.1016/j.neuroimage.2023.120346. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases. However, the AD mechanism has not yet been fully elucidated to date, hindering the development of effective therapies. In our work, we perform a brain imaging genomics study to link genetics, single-cell gene expression data, tissue-specific gene expression data, brain imaging-derived volumetric endophenotypes, and AD diagnosis to discover potential underlying neurobiological pathways for AD. To do so, we perform brain-wide genome-wide colocalization analyses to integrate multidimensional imaging genomic biobank data. Specifically, we use (1) the individual-level imputed genotyping data and magnetic resonance imaging (MRI) data from the UK Biobank, (2) the summary statistics of the genome-wide association study (GWAS) from multiple European ancestry cohorts, and (3) the tissue-specific cis-expression quantitative trait loci (cis-eQTL) summary statistics from the GTEx project. We apply a Bayes factor colocalization framework and mediation analysis to these multi-modal imaging genomic data. As a result, we derive the brain regional level GWAS summary statistics for 145 brain regions with 482,831 single nucleotide polymorphisms (SNPs) followed by posthoc functional annotations. Our analysis yields the discovery of a potential AD causal pathway from a systems biology perspective: the SNP chr10:124165615:G>A (rs6585827) mutation upregulates the expression of BTBD16 gene in oligodendrocytes, a specialized glial cells, in the brain cortex, leading to a reduced risk of volumetric loss in the entorhinal cortex, resulting in the protective effect on AD. We substantiate our findings with multiple evidence from existing imaging, genetic and genomic studies in AD literature. Our study connects genetics, molecular and cellular signatures, regional brain morphologic endophenotypes, and AD diagnosis, providing new insights into the mechanistic understanding of the disease. Our findings can provide valuable guidance for subsequent therapeutic target identification and drug discovery in AD.

PMID:37634885 | DOI:10.1016/j.neuroimage.2023.120346

J Arthroplasty. 2023 Aug 25:S0883-5403(23)00865-3. doi: 10.1016/j.arth.2023.08.055. Online ahead of print.

ABSTRACT

BACKGROUND: The use of antibiotic-impregnated cement during two-stage revision arthroplasty for periprosthetic joint infection poses a risk of renal complications following spacer insertion. This systematic review aimed to investigate the rate of acute kidney injury (AKI) following antibiotic-loaded spacer insertion and to identify risk factors associated with this complication.

METHODS: A systematic review was performed using PubMed, Cochrane Central, and Scopus databases. All clinical studies that documented renal complications following antibiotic-loaded spacer insertion for periprosthetic knee (TKA) or hip (THA) infection were included. Articles that combined THA and TKA outcomes were also included and labeled ‘THA+TKA.’ Descriptive statistics were analyzed when data were available.

RESULTS: There were 24 studies (9 THA, 7 TKA, 8 THA+TKA) included. Mean incidences of spacer-related AKI across THA, TKA, and THA+TKA cohorts were 4.2 (range, 0 to 10%), 14 (range, 0 to 19%), and 27% (range, 0 to 35%), respectively. The most common patient-related risk factors for AKI were underlying CKD or high baseline creatinine, low preoperative hemoglobin, and blood transfusion requirement. Spacer-related risk factors included high antibiotic dosage (>3.6 g/cement batch) and antibiotic type. While most recovered without complication, select patients required hemodialysis for acute management (2 THA, 18 THA+TKA) and/or developed chronic kidney disease (CKD) (8 TKA, 8 THA).

CONCLUSION: The rate of AKI following spacer insertion was high and likely under-reported in the literature. Surgeons should be cognizant of this devastating complication and should closely monitor at-risk patients for AKI following antibiotic-loaded spacer insertion.

PMID:37634877 | DOI:10.1016/j.arth.2023.08.055

J Pharm Sci. 2023 Aug 25:S0022-3549(23)00337-4. doi: 10.1016/j.xphs.2023.08.018. Online ahead of print.

ABSTRACT

In-vitro models are available in the literature for predicting the volume of distribution at steady-state (Vd_ss) of drugs. The mechanistic model refers to the tissue composition-based model (TCM), which includes important factors that govern Vd_ss such as drug physiochemistry and physiological data. The recognized TCM published by Rodgers and Rowland (TCM-RR) and a subsequent adjustment made by Simulations Plus Inc. (TCM-SP) have been shown to be generally less accurate with neutral compared to ionized drugs. Therefore, improving these models for neutral drugs becomes necessary. The objective of this study was to propose a new TCM for improving the prediction of Vd_ss for neutral drugs. The new TCM included two modifications of the published models (i) accentuate the effect of the blood-to-plasma ratio (BPR) that should cover permeated molecules across the biomembranes, which is lacking in these models for neutral compounds, and (ii) use a different approach to estimate the binding in tissues. The new TCM was validated with a large dataset of 202 commercial and proprietary compounds including preclinical and clinical data. All scenario datasets were predicted more accurately with the TCM-New, whereas all statistical parameters indicate that the TCM-New showed significant improvements in terms of accuracy over the TCM-RR and TCM-SP. Predictions of Vd_ss were frequently more accurate for the TCM-new with 83% within twofold error versus only 50% for the TCM-RR. Overall, the new TCM incorporating BPR significantly improved the Vd_ss predictions in animals and humans for neutral drugs, and, hence, has the potential to better support the drug discovery and facilitate the first-in-human predictions.

PMID:37634869 | DOI:10.1016/j.xphs.2023.08.018

Adv Nutr. 2023 Aug 25:S2161-8313(23)01358-3. doi: 10.1016/j.advnut.2023.08.009. Online ahead of print.

ABSTRACT

BACKGROUND: Vitamin A deficiency (VAD) increases risk for morbidity and mortality. Food-based approaches offer one strategy to improve vitamin A status.

OBJECTIVE: This systematic review assessed evidence of the effects of food-based approaches on the vitamin A status of women and children under five years.

METHODS: VAD was defined as clinical ocular symptoms, such as loss of vision, and/or retinol plasma or serum concentration <0.70 μmol/L. Searches on food-based approaches to improve vitamin A status were conducted for the period 2011-2022 on PubMed, CINHAL, Web of Science, and Google Scholar using PRISMA guidelines. English language publications were included. Case studies, unpublished dissertations, and non-peer-reviewed studies were excluded.

RESULTS: This review comprises 24 of 27,322 identified studies; 23 included studies focused on provitamin A carotenoids. There were 17, 214 participants across the 24 studies with sample sizes ranging from 8 to 3571 individuals. Intervention studies spanned from three weeks to two years. Fifteen (63%) studies were randomized control trials, seven were cross-sectional, and two were longitudinal studies. Most studies (N = 21) used biochemical measurements, e.g. serum retinol, to assess vitamin A status; other studies used clinical symptoms (e.g. xerophtalmia) or dietary intake. Thirteen (54%) studies reported a statistically significant effect of food-based interventions (N = 8) or an association of diet (N= 5) on vitamin A status.

CONCLUSIONS: This systematic review indicated that some food-based interventions improved vitamin A status, thus offering a safe and effective delivery mechanism for vitamin A. There appeared to be significant association between vitamin A status and consumption of foods with high concentrations of preformed vitamin A and provitamin A carotenoids. Differences across studies in regard to the period of evaluation, food approaches used, and statistical power may explain the lack of effectiveness of food-based approaches on vitamin A status in some studies.

PMID:37634852 | DOI:10.1016/j.advnut.2023.08.009