Nevin Manimala

J Am Acad Orthop Surg. 2023 Oct 1;31(19):e845-e858. doi: 10.5435/JAAOS-D-23-00063. Epub 2023 Aug 21.

ABSTRACT

INTRODUCTION: Acute blood loss anemia requiring allogeneic blood transfusion is still a postoperative complication of total knee arthroplasty (TKA). This study aimed to use machine learning models for the prediction of blood transfusion after primary TKA and to identify contributing factors.

METHODS: A total of 2,093 patients who underwent primary TKA at our institution were evaluated using data extracted from the hospital quality improvement database to identify patient demographics and surgical variables that may be associated with blood transfusion. A multilayer perceptron neural network (MPNN) machine learning algorithm was used to predict risk factors for blood transfusion and factors associated with increased length of stay. Statistical analyses including bivariate correlate analysis, Chi-Square test, and Student t-test were performed for demographic analysis and to determine the correlation between blood transfusion and other variables.

RESULTS: The results demonstrated important factors associated with transfusion rates, including preoperative hemoglobin level, preoperative creatinine level, length of surgery, simultaneous bilateral surgeries, tranexamic acid usage, American Society of Anesthesiologists Physical Status score, preoperative albumin level, ethanol usage, preoperative anticoagulation medications, age, and TKA type (conventional versus robotic-assisted). Patients who underwent a blood transfusion had a markedly greater length of stay than those who did not. The MPNN machine learning model achieved excellent performance across discrimination (AUC = 0.894).

DISCUSSION: The MPNN machine learning model showed its power as a statistical analysis tool to predict the ranking of factors for blood transfusion. Traditional statistics are unable to differentiate importance or predict in the same manner as a machine learning model.

CONCLUSION: This study demonstrated that MPNN for the prediction of patient-specific blood transfusion rates after TKA represented a novel application of machine learning with the potential to improve preoperative planning for treatment outcomes.

PMID:37733328 | DOI:10.5435/JAAOS-D-23-00063

J Trauma Acute Care Surg. 2023 Sep 21. doi: 10.1097/TA.0000000000004142. Online ahead of print.

ABSTRACT

BACKGROUND: Activated Protein C (aPC) plays dual roles after injury, driving both trauma-induced coagulopathy (TIC) by cleaving, and thus inactivating, factors Va and VIIIa and depressing fibrinolysis while also mediating an inflammomodulatory milieu via protease activated receptor-1 (PAR-1) cytoprotective signaling. Because of this dual role, it represents and ideal target for study and therapeutics after trauma. A known aPC variant, 3K3A-aPC, has been engineered to preserve cytoprotective activity while retaining minimal anticoagulant activity rendering it potentially ideal as a cytoprotective therapeutic after trauma. We hypothesized that 3K3A-aPC would mitigate the endotheliopathy of trauma by protecting against endothelial permeability.

METHODS: We used electric cell-substrate impedance sensing (ECIS) to measure permeability changes in real time in primary endothelial cells. These were cultured, grown to confluence, and treated with a 2 μg/mL solution of 3K3A-aPC at 180, 120, 60, 30 minutes prior to stimulation with ex vivo plasma taken from severely injured trauma patients (ISS > 15 and BD < -6) (TP). Cells treated with thrombin and untreated cells were included in this study as control groups. Permeability changes were recorded in real time via ECIS for 30 minutes after treatment with TP. We quantified permeability changes in the control and treatment groups as area under the curve (AUC). Rac1/RhoA activity was also compared between these groups. Statistical significance was determined by one-way ANOVA followed by a post hoc analysis using Tukey’s multiple comparison’s test.

RESULTS: Treatment with aPC mitigated endothelial permeability induced by ex vivo trauma plasma at all pre-treatment time points. The AUC of the 30-minute 3K3A-aPC pre-treatment group was higher than TP alone (mean diff. 22.12 95% CI [13.75, 30.49], p < 0.0001) (Figure). Moreover, the AUC of the 60, 120, and 180-minute pre-treatment groups was also higher than TP alone (mean diff. 16.30 95% CI [7.93, 24.67], 19.43 95% CI [11.06, 27.80], and 18.65 95% CI [10.28, 27.02], all p < .0001 respectively. Rac1/RhoA activity was higher in the aPC pre-treatment group when compared to all other groups (p < 0.01).

CONCLUSIONS: Pre-treatment with 3K3A-aPC, which retains its cytoprotective function but has only ~5% of its anti-coagulant function, abrogates the effects of trauma-induced endotheliopathy. This represents a potential therapeutic treatment for dysregulated thrombo-inflammation for injured patients by minimizing aPC’s role in trauma-induced coagulopathy while concurrently amplifying its essential cytoprotective function.

LEVEL OF EVIDENCE: Level III, Prognostic/Epidemiological.

PMID:37733304 | DOI:10.1097/TA.0000000000004142

J Integr Complement Med. 2023 Sep 21. doi: 10.1089/jicm.2022.0809. Online ahead of print.

ABSTRACT

Background: To evaluate the efficacy and safety of Keluoxin (KLX) capsules and provide validated evidence for the application of KLX in the treatment of diabetic kidney disease (DKD). Methods: A multicenter, randomized, double-blind, placebo-controlled trial design was used to screen 129 patients with DKD (urinary albumin-to-creatinine ratio [UACR]: male, 2.5-30 mg/mmol; female, 3.5-30 mg/mmol) and with Qi and Yin deficiency and blood stasis symptoms. Written informed consent was obtained from all patients. The patients were randomly divided into KLX and control groups. The KLX group was orally administered KLX (6 g/day) and irbesartan tablets (150 mg/day), whereas the control group was administered KLX placebo (6 g/day) and irbesartan tablets (150 mg/day). Patients were observed for 24 weeks to evaluate the natural logarithm of the UACR (log-UACR), the odds ratio (OR) for a sustained increase in the UACR of at least 30% and 40%, estimated glomerular filtration rate (eGFR), changes in symptoms and quality-of-life scores, and adverse events. Results: The changes of the natural log-UACR during the 24 weeks compared with baseline in the KLX group were better than those in the control group (LS mean ± standard error, -0.26 ± 0.10 vs. 0.01 ± 0.09, p = 0.0292). The incidence of a sustained increase in the UACR of at least 30% and 40% was found to be significantly lower in the KLX group (OR, 0.26; 95% confidence interval [CI], 0.09-0.75; OR, 0.29; 95% CI, 0.10-0.82). Changes in symptoms and quality-of-life scores in the KLX group were better than those in the control group. There was no statistically significant difference in eGFR or the incidence of adverse events between the groups. Conclusions: Overall, these results suggest that KLX capsules combined with irbesartan can reduce microalbuminuria, relieve the symptoms, and improve the quality of life for patients with type 2 early DKD compared with the use of irbesartan alone. Trial registration: Chinese Clinical Trial Registry, registration number: ChiCTR2100052764.

PMID:37733303 | DOI:10.1089/jicm.2022.0809

Int J Cardiovasc Imaging. 2023 Sep 21. doi: 10.1007/s10554-023-02949-0. Online ahead of print.

ABSTRACT

Advances in image reconstruction using either single or multimodality imaging data provide increasingly accurate three-dimensional (3D) patient’s arterial models for shear stress evaluation using computational fluid dynamics (CFD). We aim to evaluate the impacts on endothelial shear stress (ESS) derived from a simple image reconstruction using 3D-quantitative coronary angiography (3D-QCA) versus a multimodality reconstruction method using optical coherence tomography (OCT) in patients’ vessels treated with bioresorbable scaffolds. Seven vessels at baseline and five-year follow-up of seven patients from a previous CFD investigation were retrospectively selected for a head-to-head comparison of angiography-derived versus OCT-derived ESS. 3D-QCA significantly underestimated the minimum stent area [MSA] (-2.38mm²) and the stent length (-1.46 mm) compared to OCT-fusion method reconstructions. After carefully co-registering the region of interest for all cases with a sophisticated statistical method, the difference in MSA measurements as well as the inability of angiography to visualise the strut footprint in the lumen surface have translated to higher angiography-derived ESS than OCT-derived ESS (1.76 Pa or 1.52 times for the overlapping segment). The difference in ESS widened with a more restricted region of interest (1.97 Pa or 1.63 times within the scaffold segment). Angiography and OCT offer two distinctive methods of ESS calculation. Angiography-derived ESS tends to overestimate the ESS compared to OCT-derived ESS. Further investigations into ESS analysis resolution play a vital role in adopting OCT-derived ESS.

PMID:37733283 | DOI:10.1007/s10554-023-02949-0

Eur J Clin Pharmacol. 2023 Sep 21. doi: 10.1007/s00228-023-03569-2. Online ahead of print.

ABSTRACT

PURPOSE: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use.

METHODS: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ.

RESULTS: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability.

CONCLUSION: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.

PMID:37733278 | DOI:10.1007/s00228-023-03569-2

Euro Surveill. 2023 Sep;28(38). doi: 10.2807/1560-7917.ES.2023.28.38.2200938.

ABSTRACT

BackgroundThe sensitivity and specificity of selected antigen detection rapid diagnostic tests (AG-RDTs) for SARS-CoV-2 were determined in the unvaccinated population when the Delta variant was circulating. Viral loads, dynamics, symptoms and tissue tropism differ between Omicron and Delta.AimWe aimed to compare AG-RDT sensitivity and specificity in selected subgroups during Omicron vs Delta circulation.MethodsWe retrospectively paired AG-RDT results with PCRs registered in Czechia’s Information System for Infectious Diseases from 1 to 25 December 2021 (Delta, n = 20,121) and 20 January to 24 February 2022 (Omicron, n = 47,104).ResultsWhen confirmatory PCR was conducted on the same day as AG-RDT as a proxy for antigen testing close to peak viral load, the average sensitivity for Delta was 80.4% and for Omicron 81.4% (p < 0.05). Sensitivity in vaccinated individuals was lower for Omicron (OR = 0.94; 95% confidence interval (CI): 0.87-1.03), particularly in reinfections (OR = 0.83; 95% CI: 0.75-0.92). Saliva AG-RDT sensitivity was below average for both Delta (74.4%) and Omicron (78.4%). Tests on the European Union Category A list had higher sensitivity than tests in Category B. The highest sensitivity for Omicron (88.5%) was recorded for patients with loss of smell or taste, however, these symptoms were almost 10-fold less common than for Delta. The sensitivity of AG-RDTs performed on initially asymptomatic individuals done 1, 2 or 3 days before a positive PCR test was consistently lower for Omicron compared with Delta.ConclusionSensitivity for Omicron was lower in subgroups that may become more common if SARS-CoV-2 becomes an endemic virus.

PMID:37733239 | DOI:10.2807/1560-7917.ES.2023.28.38.2200938

Ir J Med Sci. 2023 Sep 21. doi: 10.1007/s11845-023-03526-z. Online ahead of print.

ABSTRACT

BACKGROUND: The major changes in the timing of meals during Ramadan may be challenging for hypothyroid patients on levothyroxine. We aimed to study the effect of Ramadan fasting on thyroid functions in hypothyroid patients taking levothyroxine.

METHODS: We did a comprehensive search of 8 databases for Randomized controlled studies (RCTs) and observational studies investigating the effect of Ramadan fasting on thyroid functions in hypothyroid individuals taking levothyroxine. Relevant data was extracted and analyzed. Mean difference (MD) and standard deviation (SD) were used to evaluate the continuous data. Risk ratios (RR) with a 95% confidence interval were used for outcomes constituting dichotomous data. National Institutes of Health (NIH) tools were used to assess the risk of bias.

RESULTS: Fourteen studies met our inclusion criteria, 3 RCTs, and 11 observational studies, all designed as pre-post studies. Ramadan fasting was associated with a statistically significant increase in TSH in patients who were euthyroid before Ramadan (MD = -0.76 [95% CI; -1.27, -0.25]). However, free thyroxine (FT4) was found to be stable (MD = 0.01, [95% CI; -0.03, 0.06]). All timing points were associated with a significant increase in TSH levels after Ramadan, pre-iftar (MD = -0.69 [95% CI; -1.03, -0.36]), post-iftar (MD = -0.76 [95% CI; -1.12, -0.39]), and pre-suhoor (MD = -1.19 [95% CI; -2.18, -0.19]).

CONCLUSION: TSH increases significantly after Ramadan. No timing point has superiority in maintaining thyroid control. However, choosing the timing should be individualized according to the patient’s preference to guarantee the most possible compliance.

PMID:37733226 | DOI:10.1007/s11845-023-03526-z

Jpn J Radiol. 2023 Sep 21. doi: 10.1007/s11604-023-01486-z. Online ahead of print.

ABSTRACT

The effectiveness and precision of disease diagnosis and treatment have increased, thanks to developments in clinical imaging over the past few decades. Science is developing and progressing steadily in imaging modalities, and effective outcomes are starting to show up as a result of the shorter scanning periods needed as well as the higher-resolution images generated. The choice of one clinical device over another is influenced by technical disparities among the equipment, such as detection medium, shorter scan time, patient comfort, cost-effectiveness, accessibility, greater sensitivity and specificity, and spatial resolution. Lately, computational algorithms, artificial intelligence (AI), in particular, have been incorporated with diagnostic and treatment techniques, including imaging systems. AI is a discipline comprised of multiple computational and mathematical models. Its applications aided in manipulating sophisticated data in imaging processes and increased imaging tests’ accuracy and precision during diagnosis. Computed tomography (CT), positron emission tomography (PET), and Single Photon Emission Computed Tomography (SPECT) along with their corresponding radiation detectors have been reviewed in this study. This review will provide an in-depth explanation of the above-mentioned imaging modalities as well as the radiation detectors that are their essential components. From the early development of these medical instruments till now, various modifications and improvements have been done and more is yet to be established for better performance which calls for a necessity to capture the available information and record the gaps to be filled for better future advances.

PMID:37733205 | DOI:10.1007/s11604-023-01486-z

Disabil Rehabil. 2023 Sep 21:1-9. doi: 10.1080/09638288.2023.2259311. Online ahead of print.

ABSTRACT

Purpose: To understand the circumstances, causes and consequences of falls experienced by individuals with subacute SCI, and to explore their perspectives on how falls/fall risk impacted their transition to community living.Materials and methods: Sixty adults with subacute SCI participated. A sequential explanatory mixed methods design was adopted. In Phase I, falls were monitored for six months post-inpatient rehabilitation discharge through a survey. In Phase II, a qualitative focus group (n = 5) was held to discuss participants’ perspectives on Phase I results and falls/fall risk. Descriptive statistics and thematic analysis were used to analyze Phase I and II data, respectively.Results: Falls commonly occurred in the daytime, at home and about half resulted in minor injury. Three themes reflecting participants’ perspectives were identified in Phase II. 1) Lack of preparedness to manage fall risk upon returning home from inpatient rehabilitation. 2) Adjusting to increased fall risk following discharge from inpatient rehabilitation. 3) Psychological impact of the transition to living at home with an increased fall risk.Conclusions: The findings highlight the need for fall prevention initiatives during subacute SCI, when individuals are learning to manage their increased fall risk.

PMID:37732508 | DOI:10.1080/09638288.2023.2259311

J Integr Bioinform. 2023 Sep 21. doi: 10.1515/jib-2022-0029. Online ahead of print.

ABSTRACT

Many important aspects of biological knowledge at the molecular level can be represented by pathways. Through their analysis, we gain mechanistic insights and interpret lists of interesting genes from experiments (usually omics and functional genomic experiments). As a result, pathways play a central role in the development of bioinformatics methods and tools for computing predictions from known molecular-level mechanisms. Qualitative as well as quantitative knowledge about pathways can be effectively represented through biochemical networks linking the biochemical reactions and the compounds (e.g., proteins) occurring in the considered pathways. So, repositories providing biochemical networks for known pathways play a central role in bioinformatics and in systems biology. Here we focus on Reactome, a free, comprehensive, and widely used repository for biochemical networks and pathways. In this paper, we: (1) introduce a tool StARGate-X (STatistical Analysis of the Reactome multi-GrAph Through nEtworkX) to carry out an automated analysis of the connectivity properties of Reactome biochemical reaction network and of its biological hierarchy (i.e., cell compartments, namely, the closed parts within the cytosol, usually surrounded by a membrane); the code is freely available at https://github.com/marinoandrea/stargate-x; (2) show the effectiveness of our tool by providing an analysis of the Reactome network, in terms of centrality measures, with respect to in- and out-degree. As an example of usage of StARGate-X, we provide a detailed automated analysis of the Reactome network, in terms of centrality measures. We focus both on the subgraphs induced by single compartments and on the graph whose nodes are the strongly connected components. To the best of our knowledge, this is the first freely available tool that enables automatic analysis of the large biochemical network within Reactome through easy-to-use APIs (Application Programming Interfaces).

PMID:37732505 | DOI:10.1515/jib-2022-0029