Tag: pubmed

Scand J Med Sci Sports. 2023 Jan 26. doi: 10.1111/sms.14322. Online ahead of print.

ABSTRACT

PURPOSE: To (1) identify neuromuscular and biomechanical injury risk factors in elite youth soccer players and (2) assess the predictive ability of a machine learning approach.

MATERIAL AND METHODS: Fifty-six elite male youth soccer players (age: 17.2 ± 1.1 years; height: 179 ± 8 cm; mass: 70.4 ± 9.2 kg) performed a 3D motion analysis, postural control testing, and strength testing. Non-contact lower extremities injuries were documented throughout 10 months. A least absolute shrinkage and selection operator (LASSO) regression model was used to identify the most important injury predictors. Predictive performance of the LASSO model was determined in a leave-one-out (LOO) prediction competition.

RESULTS: Twenty-three non-contact injuries were registered. The LASSO model identified concentric knee extensor peak torque, hip transversal plane moment in the single-leg drop landing task and COP sway in the single-leg stance test as the three most important predictors for injury in that order. The LASSO model was able to predict injury outcomes with a likelihood of 58% and an AUC of 0.63 (sensitivity = 35%; specificity = 79%).

CONCLUSION: The three most important variables for predicting the injury outcome suggest the importance of neuromuscular and biomechanical performance measures in elite youth soccer. These preliminary results may have practical implications for future directions in injury risk screening and planning, as well as for the development of customized training programs to counteract intrinsic injury risk factors. However, the poor predictive performance of the final model confirms the challenge of predicting sports injuries, and the model must therefore be evaluated in larger samples.

PMID:36703247 | DOI:10.1111/sms.14322

Immunology. 2023 Jan 26. doi: 10.1111/imm.13627. Online ahead of print.

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer. Neoadjuvant chemotherapy has proven efficacy in its treatment, and a pathological complete response (pCR) to therapy is predictive of improved long-term survival. The immune response is key to successful neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumor-infiltrating lymphocytes (TILs) in pre-treated tumor tissue samples and the likelihood of achieving pCR. Here we studied systemic immune mediators from volunteer TNBC patients before undergoing neoadjuvant chemotherapy to determine the systemic response association with TIL intensity, treatment response and survival. Patients were classified into pCR responder or non-responder at time of surgery. We found higher levels of immune mediators before treatment began in patients that went on to be pCR responders vs. non-pCR, with AUC values of 0.64 – 0.80. We also observed a positive correlation between inflammatory systemic immune mediators and the percentage of TILs in pCR responder patients. Combining TILs and systemic immune mediator levels provided stronger AUC values (range of 0.72 – 0.82). Lastly, performing a progression free survival analysis with several of the systemic cytokines that predict pCR, segregated the patients into long and short survival groups based on high and low production of the cytokines, respectively. Our study demonstrates that circulating cytokines, before treatment begins, predict pCR in TNBC patients treated with neoadjuvant chemotherapy. Moreover, they may act as a surrogate marker of high TILs or together with TILs to better predict pCR and survival. This article is protected by copyright. All rights reserved.

PMID:36703241 | DOI:10.1111/imm.13627

Anim Microbiome. 2023 Jan 26;5(1):6. doi: 10.1186/s42523-023-00225-z.

ABSTRACT

BACKGROUND: Nondrug supplement strategies to improve gut health have largely focused on the effects of individual compounds to improve one aspect of gut homeostasis. However, there is no comprehensive assessment of the reproducible effects of oral, short-term, low-level colostrum supplementation on gut inflammation status that are specific to the ileum. Herein, a chicken animal model highly responsive to even mild gut inflammatory stimuli was employed to compare the outcomes of feeding a standard diet (CON) to those of CON supplemented with a centrifuge-defatted bovine colostrum (BC) or a nonfat dried milk (NFDM) control on the efficiency of nutrient use, ileal morphology, gut nitro-oxidative inflammation status, metabolites, and the composition of the microbiota.

RESULTS: A repeated design, iterative multiple regression model was developed to analyze how BC affected ileal digesta-associated anti-inflammatory metabolite abundance coincident with observed changes in the ileal microbiome, mitigation of epithelial inflammation, and ileal surface morphology. An improved whole body nutrient use efficiency in the BC group (v CON and NFDM) coincided with the observed increased ileum absorptive surface and reduced epithelial cell content of tyrosine-nitrated protein (NT, biomarker of nitro-oxidative inflammatory stress). Metabolome analysis revealed that anti-inflammatory metabolites were significantly greater in abundance in BC-fed animals. BC also had a beneficial BC impact on microbiota, particularly in promoting the presence of the bacterial types associated with eubiosis and the segmented filamentous bacteria, Candidatus Arthromitus.

CONCLUSION: The data suggest that an anti-inflammatory environment in the ileum was more evident in BC than in the other feeding groups and associated with an increased content of statistically definable groups of anti-inflammatory metabolites that appear to functionally link the observed interactions between the host’s improved gut health with an observed increase in whole body nutrient use efficiency, beneficial changes in the microbiome and immunometabolism.

PMID:36703224 | DOI:10.1186/s42523-023-00225-z

Genome Med. 2023 Jan 27;15(1):5. doi: 10.1186/s13073-023-01157-8.

ABSTRACT

BACKGROUND: Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans.

METHODS: We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P < .05 was considered statistically significant.

RESULTS: We present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7-35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7-37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders.

CONCLUSIONS: Early access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population.

PMID:36703223 | DOI:10.1186/s13073-023-01157-8

BMC Med Educ. 2023 Jan 26;23(1):66. doi: 10.1186/s12909-023-04047-0.

ABSTRACT

BACKGROUND: Quality improvement (QI) is a systematic approach to improving healthcare delivery with applications across all fields of medicine. However, exposure to QI is minimal in early medical education. We evaluated the effectiveness of an elective QI curriculum in teaching preclinical health professional students foundational QI concepts.

METHODS: This prospective controlled cohort study was conducted at a single academic institution. The elective QI curriculum consisted of web-based video didactics and exercises, supplemented with in-person classroom discussions. An optional hospital-based QI project was offered. Assessments included pre- and post-intervention surveys evaluating QI skills and beliefs and attitudes, quizzes, and Quality Improvement Knowledge Application Tool-Revised (QIKAT-R) cases. Within-group pre-post and between-group comparisons were performed using descriptive statistics.

RESULTS: Overall, 57 preclinical medical or physician assistant students participated under the QI curriculum group (N = 27) or control group (N = 30). Twenty-three (85%) curriculum students completed a QI project. Mean quiz scores were significantly improved in the curriculum group from pre- to post-assessment (Quiz 1: 2.0, P < 0.001; Quiz 2: 1.7, P = 0.002), and the mean differences significantly differed from those in the control group (Quiz 1: P < 0.001; Quiz 2: P = 0.010). QIKAT-R scores also significantly differed among the curriculum group versus controls (P = 0.012). In the curriculum group, students had improvements in their confidence with all 10 QI skills assessed, including 8 that were significantly improved from pre- to post-assessment, and 4 with significant between-group differences compared with controls. Students in both groups agreed that their medical education would be incomplete without a QI component and that they are likely to be involved in QI projects throughout their medical training and practice.

CONCLUSIONS: The elective QI curriculum was effective in guiding preclinical students to develop their QI knowledge base and skillset. Preclinical students value QI as an integral component of their medical training. Future directions involve evaluating the impact of this curriculum on clinical clerkship performance and across other academic institutions.

PMID:36703204 | DOI:10.1186/s12909-023-04047-0

Cost Eff Resour Alloc. 2023 Jan 26;21(1):10. doi: 10.1186/s12962-023-00420-4.

ABSTRACT

OBJECTIVE: Renal cell carcinoma (RCC) is the most common type of kidney cancer. VEGF inhibitors and mTORs are the most common therapeutic options among the different classes of available treatments. In this study, the effectiveness of Everolimus was compared to Temsirolimus, and Everolimus plusLenvatinib in renal cell carcinoma patients by review of the international clinical evidence.

MATERIALS AND METHODS: A systematic review was conducted and all relevant published clinical studies on the efficacy and cost-effectiveness of Everolimus, Temsirolimus, and Lenvatinib plus Everolimus were searched comprehensively in electronic databases including Pubmed, Scopus, Medline, Cochrane Library, and ISI web of science. The Q score and I2 test checked the Heterogeneity and publication bias test, respectively. Egger’s test and Begg’s test were used to checking publication bias. The hazard ratio (HR) of included studies and subclass analysis were estimated by fixed and random effect models.

RESULTS: Out of 1816 found studies, ultimately, were included considering inclusion and exclusion criteria. None of these studies evaluated all three treatment strategies together and each study was about one strategy. Only one study was found for Everolimus plus Lenvatinib, so it was excluded from meta-analysis. Overall, data from 526 patients on Temsirolimus and 648 patients on Everolimus were included in Meta-Analysis. Accordingly, the efficacy of Everolimus and Temsirolimus was not statistically significant in assessed outcomes (PFS, TTSF, and death). However, Everlimus is superior to Temsirolimus in OS (Q = 3.61, p-value: 0.462, I2 = 0%). No heterogeneity or bias was detected.

CONCLUSION: According to the results of this study, Everolimus could be related to an increase of OS versus Temsirolimus as a second line treatment of ORCC patients.

PMID:36703202 | DOI:10.1186/s12962-023-00420-4

Fluids Barriers CNS. 2023 Jan 26;20(1):7. doi: 10.1186/s12987-023-00407-6.

ABSTRACT

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and partially reversible form of dementia, characterized by impaired interactions between multiple brain regions. Because of the presence of comorbidities and a lack of accurate diagnostic and prognostic biomarkers, only a minority of patients receives disease-specific treatment. Recently, resting-state functional-magnetic resonance imaging (rs-fMRI) has demonstrated functional connectivity alterations in inter-hemispheric, frontal, occipital, default-mode (DMN) and motor network (MN) circuits. Herein, we report our experience in a cohort of iNPH patients that underwent cerebrospinal fluid (CSF) dynamics evaluation and rs-fMRI. The study aimed to identify functional circuits related to iNPH and explore the relationship between DMN and MN recordings and clinical modifications before and after infusion and tap test, trying to understand iNPH pathophysiology and to predict the best responders to ventriculoperitoneal shunt (VPS) implant.

METHODS: We prospectively collected data regarding clinical assessment, neuroradiological findings, lumbar infusion and tap test of thirty-two iNPH patients who underwent VPS implant. Rs-fMRI was performed using MELODIC-ICA both before and after the tap test. Rs-fMRI data of thirty healthy subjects were also recorded.

RESULTS: At the baseline, reduced z-DMN and z-MN scores were recorded in the iNPH cohort compared with controls. Higher z-scores were recorded in more impaired patients. Both z-scores significantly improved after the tap test except in subjects with a low resistance to outflow value and without a significant clinical improvement after the test. A statistically significant difference in mean MN connectivity scores for tap test responders and non-responders was demonstrated both before (p = 0.0236) and after the test (p = 0.00137). A statistically significant main effect of the tap test on DMN connectivity after CSF subtraction was recorded (p = 0.038).

CONCLUSIONS: Our results suggest the presence of a partially reversible plasticity functional mechanism in DMN and MN. Low values compensate for the initial stages of the disease, while higher values of z-DMN were recorded in older patients with a longer duration of symptoms, suggesting an exhausted plasticity compensation. The standardization of this technique could play a role as a non-invasive biomarker in iNPH disease, suggesting the right time for surgery. Trial Registration Prot. IRB 090/2021.

PMID:36703181 | DOI:10.1186/s12987-023-00407-6

J Foot Ankle Res. 2023 Jan 26;16(1):2. doi: 10.1186/s13047-023-00601-7.

ABSTRACT

AIM: This study aims to explore the feasibility of using serial MRI without contrast in the monitoring of Charcot neuroarthropathy to reduce duration of immobilisation of the foot, in order to decide whether a large-scale trial is warranted.

METHODS: A multicentre, randomised, prospective, two arm, open, feasibility study (CADOM) of people with diabetes with a suspected or confirmed diagnosis of Charcot neuroarthropathy. Participants were randomised (1:1) to ‘standard care plus’, including repeated foot temperature measurements and X-rays, or the intervention arm, with additional three-monthly MRI, until remission of Charcot neuroarthropathy or a maximum 12 months (active phase). Participants were then followed-up for a further 6 months, post remission to monitor for relapse of the Charcot neuroarthropathy (follow-up phase). Feasibility outcomes were recruitment, retention, data completeness, adherence to study procedures and safety of the intervention MRI. We also collected clinical efficacy outcomes, this included time in cast/off-loading device which will be the primary outcome of a future definitive trial. Finally, we collected patient reported outcomes, and data on health and social care usage.

RESULTS: One-hundred and five people were assessed for eligibility at five sites. 64/105 potential participants meet the eligibility criteria to participate in the study. Forty-three participants were randomised: 20 to standard care plus and 23 to MRI intervention. The main reason for ineligibility was a previous episode of Charcot neuroarthropathy. Thirteen participants were withdrawn post-randomisation due to an alternative diagnosis being made. Of the remaining 30 participants, 19 achieved remission, 6 had not gone into remission at the end of the 12 month active phase so exited the study. Five participants were lost to follow-up. Of the MRIs that were not disrupted by COVID-19 pandemic 26/31 (84%) were completed. For the visits that were conducted face-to-face, completion rates of patient-reported outcome measures were between 71 and 100%. There were no safety incidents associated with the intervention MRI. As this was a feasibility study it was not designed to test the effectiveness of serial MRI in diagnosing remission. The time in cast/off-loading device was 235 (±108.3) days for the standard care plus arm compared to 292 (±177.4) days for the intervention arm. There was no statistical difference in the time in cast/off-loading device between the two arms of the study: Hazard Ratio (HR) 0.405 (95% CI 0.140-1.172), p = 0.096.

DISCUSSION: The findings support a definitive randomised controlled trial to evaluate the effectiveness of MRI in diagnosing remission in Charcot neuroarthropathy. The rates of recruitment, retention, data, and MRI completeness show that a definitive study is feasible.

STUDY REGISTRATION: ISRCTN, 74101606 . Registered on 6 November 2017.

PMID:36703174 | DOI:10.1186/s13047-023-00601-7

Reprod Biol Endocrinol. 2023 Jan 26;21(1):8. doi: 10.1186/s12958-023-01065-x.

ABSTRACT

STUDY QUESTION: To construct prediction models based on the Bayesian network (BN) learning method for the probability of fertilization failure (including low fertilization rate [LRF] and total fertilization failure [TFF]) in assisted reproductive technology (ART) treatment. A BN model was developed to predict TFF/LFR. The model showed relatively high calibration in external validation, which could facilitate the identification of risk factors for fertilization disorders and improve the efficiency of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.

WHAT IS KNOWN ALREADY: The prediction of TFF/LFR is very complex. Although some studies attempted to construct prediction models for TFF/LRF, most of the reported models were based on limited variables and traditional regression-based models, which are unsuitable for analyzing real-world clinical data. Therefore, none of the reported models have been widely used in routine clinical practice. To date, BN modeling analysis is a prominent and increasingly popular machine learning method that is powerful in dealing with dynamic and complex real-world data.

STUDY DESIGN, SIZE, DURATION: A retrospective study was performed with 106,640 fresh embryo IVF/ICSI cycles from 2009 to 2019 in one of China’s largest reproductive health centers.

PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 106, 640 cycles were included in this study, including 97,102 controls, 4,339 LFR cases, and 5,199 TFF cases. Twenty-four predictors were initially included, including 13 female-related variables, five male-related variables, and six variables related to IVF/ICSI treatment. BN modeling analysis with tenfold cross-validation was performed to construct the predictive model for TFF/LFR. The receiver operating characteristic (ROC) curves and the corresponding area under the curves (AUCs) were used to evaluate the performance of the BN model.

MAIN RESULTS AND THE ROLE OF CHANCE: All twenty-four predictors were first organized into seven hierarchical layers in a theoretical BN model, according to prior knowledge from previous literature and clinical practice. A machine-learning BN model was generated based on real-world clinical data, containing a total of eighteen predictors, of which the infertility type, ART method, and number of retrieved oocytes directly influence the probabilities of LFR/TFF. The prediction accuracy of the BN model was 91.7%. The AUC of the TFF versus control groups was 0.779 (95% CI: 0.766-0.791), with a sensitivity of 71.2% and specificity of 70.1%; the AUC of of TFF versus LFR groups was 0.807 (95% CI: 0.790-0.824), with a sensitivity of 49.0% and specificity of 99.0%.

LIMITATIONS, REASON FOR CAUTION: First, our study was based on clinical data from a single center, and the results of this study should be further verified by external data. In addition, some critical data (e.g., the detailed IVF laboratory parameters of the sperm and oocytes used for insemination) were not available in this study, which should be given full consideration when further improving the performance of the BN model.

WIDER IMPLICATIONS OF THE FINDINGS: Based on extensive clinical real-world data, we developed a BN model to predict the probabilities of fertilization failures in ART, which provides new clues for clinical decision-making support for clinicians in formulating personalized treatment plans and further improving ART treatment outcomes.

STUDY FUNDING/COMPETING INTEREST(S): Dr. Y. Wang was supported by grants from the Beijing Municipal Science & Technology Commission (Z191100006619086). We declare that there are no conflicts of interest.

TRIAL REGISTRATION NUMBER: N/A.

PMID:36703171 | DOI:10.1186/s12958-023-01065-x

BMC Public Health. 2023 Jan 26;23(1):177. doi: 10.1186/s12889-022-14909-9.

ABSTRACT

BACKGROUND: Given the nature of the spread of SARS-CoV-2, strong regional patterns in the fatal consequences of the COVID-19 pandemic related to local characteristics such as population and health care infrastructures were to be expected. In this paper we conduct a detailed examination of the spatial correlation of deaths in the first year of the pandemic in two neighbouring countries – Germany and Poland, which, among high income countries, seem particularly different in terms of the death toll associated with the COVID-19 pandemic. The analysis aims to yield evidence that spatial patterns of mortality can provide important clues as to the reasons behind significant differences in the consequences of the COVID-19 pandemic in these two countries.

METHODS: Based on official health and population statistics on the level of counties, we explore the spatial nature of mortality in 2020 in the two countries – which, as we show, reflects important contextual differences. We investigate three different measures of deaths: the officially recorded COVID-19 deaths, the total values of excessive deaths and the difference between the two. We link them to important pre-pandemic regional characteristics such as population, health care and economic conditions in multivariate spatial autoregressive models. From the point of view of pandemic related fatalities we stress the distinction between direct and indirect consequences of COVID-19, separating the latter further into two types, the spatial nature of which is likely to differ.

RESULTS: The COVID-19 pandemic led to much more excess deaths in Poland than in Germany. Detailed spatial analysis of deaths at the regional level shows a consistent pattern of deaths officially registered as related to COVID-19. For excess deaths, however, we find strong spatial correlation in Germany but little such evidence in Poland.

CONCLUSIONS: In contrast to Germany, for Poland we do not observe the expected spatial pattern of total excess deaths and the excess deaths over and above the official COVID-19 deaths. This difference cannot be explained by pre-pandemic regional factors such as economic and population structures or by healthcare infrastructure. The findings point to the need for alternative explanations related to the Polish policy reaction to the pandemic and failures in the areas of healthcare and public health, which resulted in a massive loss of life.

PMID:36703167 | DOI:10.1186/s12889-022-14909-9