Nevin Manimala

J Magn Reson Imaging. 2021 Sep 21. doi: 10.1002/jmri.27925. Online ahead of print.

ABSTRACT

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized.

PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features.

ANIMAL MODEL: Established PBDL models.

POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group.

FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging.

ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D^* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system.

STATISTICAL TESTS: One-way ANOVA, Spearman’s rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant.

RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2^* than other livers. Spearman’s correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956.

DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation.

LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

PMID:34545977 | DOI:10.1002/jmri.27925

Clin Transplant. 2021 Sep 21:e14490. doi: 10.1111/ctr.14490. Online ahead of print.

ABSTRACT

BACKGROUND: Knowledge of metabolic processes affected by major hepatectomy (MHx), and the metabolic pathways involved in liver regeneration and recovery of function, is limited and mainly derived from animal models. Assessment of restoration of hepatic function is essential in human living liver donors (LD).

METHODS: We used a targeted metabolomic approach to longitudinally quantify changes in plasma and urine biomarkers from healthy LD. The biomarkers were analyzed before MHx and at scheduled intervals up to 12 months thereafter.

RESULTS: Marked changes were found in the concentration of 15 primary and secondary plasma bile acids. Most significant changes occurred 2 days after MHx and persisted for up to 3 months. In addition, there were significant changes in acylcarnitine, phospholipid, and amino acid metabolism. The sum of aromatic amino acids and the Fischer ratio, both metabolic markers of liver damage, and the symmetrically demethylated arginine to arginine ratio, a marker of kidney function, were affected.

CONCLUSIONS: This is the first comprehensive longitudinal study investigating metabolic processes during recovery of liver function after MHx in LD. It provides further evidence of full restoration of metabolic processes 3 months after MHx and supports future investigation to understand how metabolic changes affect donors’ hepatic function. This article is protected by copyright. All rights reserved.

PMID:34545967 | DOI:10.1111/ctr.14490

Clin Transplant. 2021 Sep 21:e14466. doi: 10.1111/ctr.14466. Online ahead of print.

ABSTRACT

The demand for transplantable kidneys continues to outstrip supply, and the risk of donor-derived infection limits utilization. The effect of donor or recipient HBV status, defined by surface antigen (HBsAg) positivity, on long-term survival outcomes of kidney transplant (KT) is unknown. We conducted a retrospective cohort study based on Organ Procurement and Transplantation Network (OPTN) data from 2000 to 2019. We identified three cohorts based on donor (D) or recipient (R) HBsAg status: D-R-, D-R+, and D+R-. Pairwise comparisons of patient survival (PS) and all-cause graft survival (GS) after propensity score matching were performed to assess the effect of HBV infection in KT recipients. Results showed that there were no statistically significant differences in PS and GS among D-R-, D-R+, and D+R- groups, nor was the patient or graft survival different between donor and recipient HBsAg+ status. Finally, in 2019 kidney discard rates were 15% higher for HBsAg+ deceased donors compared to HBsAg- donors. HBsAg+ status was not associated with worse PS or GS after KT. Prior to broadly advocating utilization of HbsAg+ kidneys, further studies assessing KT recipient morbidity and safety are necessary. This article is protected by copyright. All rights reserved.

PMID:34545965 | DOI:10.1111/ctr.14466

Med Phys. 2021 Sep;48(9):4711-4714. doi: 10.1002/mp.15170.

ABSTRACT

The Abstract is intended to provide a concise summary of the study and its scientific findings. For AI/ML applications in medical physics, a problem statement and rationale for utilizing these algorithms are necessary while highlighting the novelty of the approach. A brief numerical description of how the data are partitioned into subsets for training of the AI/ML algorithm, validation (including tuning of parameters), and independent testing of algorithm performance is required. This is to be followed by a summary of the results and statistical metrics that quantify the performance of the AI/ML algorithm.

PMID:34545957 | DOI:10.1002/mp.15170

CA Cancer J Clin. 2021 Sep 21. doi: 10.3322/caac.21695. Online ahead of print.

ABSTRACT

The Hispanic/Latino population is the second largest racial/ethnic group in the continental United States and Hawaii, accounting for 18% (60.6 million) of the total population. An additional 3 million Hispanic Americans live in Puerto Rico. Every 3 years, the American Cancer Society reports on cancer occurrence, risk factors, and screening for Hispanic individuals in the United States using the most recent population-based data. An estimated 176,600 new cancer cases and 46,500 cancer deaths will occur among Hispanic individuals in the continental United States and Hawaii in 2021. Compared to non-Hispanic Whites (NHWs), Hispanic men and women had 25%-30% lower incidence (2014-2018) and mortality (2015-2019) rates for all cancers combined and lower rates for the most common cancers, although this gap is diminishing. For example, the colorectal cancer (CRC) incidence rate ratio for Hispanic compared with NHW individuals narrowed from 0.75 (95% CI, 0.73-0.78) in 1995 to 0.91 (95% CI, 0.89-0.93) in 2018, reflecting delayed declines in CRC rates among Hispanic individuals in part because of slower uptake of screening. In contrast, Hispanic individuals have higher rates of infection-related cancers, including approximately two-fold higher incidence of liver and stomach cancer. Cervical cancer incidence is 32% higher among Hispanic women in the continental US and Hawaii and 78% higher among women in Puerto Rico compared to NHW women, yet is largely preventable through screening. Less access to care may be similarly reflected in the low prevalence of localized-stage breast cancer among Hispanic women, 59% versus 67% among NHW women. Evidence-based strategies for decreasing the cancer burden among the Hispanic population include the use of culturally appropriate lay health advisors and patient navigators and targeted, community-based intervention programs to facilitate access to screening and promote healthy behaviors. In addition, the impact of the COVID-19 pandemic on cancer trends and disparities in the Hispanic population should be closely monitored.

PMID:34545941 | DOI:10.3322/caac.21695

Brief Bioinform. 2021 Sep 20:bbab370. doi: 10.1093/bib/bbab370. Online ahead of print.

ABSTRACT

Quantitative trait locus (QTL) analyses of multiomic molecular traits, such as gene transcription (eQTL), DNA methylation (mQTL) and histone modification (haQTL), have been widely used to infer the functional effects of genome variants. However, the QTL discovery is largely restricted by the limited study sample size, which demands higher threshold of minor allele frequency and then causes heavy missing molecular trait-variant associations. This happens prominently in single-cell level molecular QTL studies because of sample availability and cost. It is urgent to propose a method to solve this problem in order to enhance discoveries of current molecular QTL studies with small sample size. In this study, we presented an efficient computational framework called xQTLImp to impute missing molecular QTL associations. In the local-region imputation, xQTLImp uses multivariate Gaussian model to impute the missing associations by leveraging known association statistics of variants and the linkage disequilibrium (LD) around. In the genome-wide imputation, novel procedures are implemented to improve efficiency, including dynamically constructing a reused LD buffer, adopting multiple heuristic strategies and parallel computing. Experiments on various multiomic bulk and single-cell sequencing-based QTL datasets have demonstrated high imputation accuracy and novel QTL discovery ability of xQTLImp. Finally, a C++ software package is freely available at https://github.com/stormlovetao/QTLIMP.

PMID:34545927 | DOI:10.1093/bib/bbab370

J Nutr Health Aging. 2021;25(8):1012-1022. doi: 10.1007/s12603-021-1666-7.

ABSTRACT

BACKGROUND: Sarcopenia is prevalent in middle-aged and older adults. A plant-based diet may be linked to changes in body composition and musculoskeletal health.

OBJECTIVE: This systematic review aimed to investigate the effects of plant-based dietary patterns on the body composition, muscle strength and function in middle-aged and older adults. PRISMA guidelines were followed.

METHOD: A systematic search was completed on databases including MEDLINE, Embase, Global Health, PREMEDLINE, Cochrane library, CINAHL and Scopus on articles published until 1st March 2019. Search terms included ‘middle-aged’, ‘older adult’, ‘plant-based diet’ and ‘muscle strength’. Title and abstract screening were conducted on 1,868 publications after deduplication. Sample size, subject characteristics, recruitment, inclusion and exclusion criteria, dietary measures, health outcome measures, statistical results and confounders were sorted by author, study type, year and country. The quality of evidence of extracted data was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools.

RESULTS/CONCLUSIONS: 17 papers were included from 31 articles selected for full review. The majority of the studies were cross-sectional studies (n = 9) and RCTs (n = 6).The remaining studies were cohort studies. Positive associations were found between plant-based dietary patterns; negative association with body composition; and inconclusive association with muscle function. However, further studies are needed to improve the understanding.

PMID:34545922 | DOI:10.1007/s12603-021-1666-7

J Nutr Health Aging. 2021;25(8):993-998. doi: 10.1007/s12603-021-1670-y.

ABSTRACT

Previous studies have investigated the association between cognitive frailty and falls among older adults in community; however, no study investigated this relationship among older patients living in hospital. This study aimed to examine the relationship of cognitive frailty with falls among older inpatients in Chinese hospital.

METHODS: This analysis consisted of 9192 older inpatients aged 65 years or over from six hospitals in China. We used FRAIL scale and Mini-Cog to assess frailty and cognitive impairment, respectively. A generalized estimating equation was used to examine the relationship between cognitive frailty and falls at 30-day follow-up.

RESULTS: Among 9192 older inpatients enrolled in this present study, the mean (SD) age was 72.40(5.72) years, with 3850(41.88%) women. The cross-sectional analysis found that after controlling for variables (age, gender, education, depression, and hospital ward cluster effect), hospitalized patients with cognitive frailty, frailty only, or cognitive impairment only at baseline were all associated with history of falls (P<0.05). At 30-day follow-up, generalized estimating equation with full-adjustment showed that inpatients with cognitive frailty were at greater risk of falls than those of non-frail and cognitive intact (OR=3.0,95%CI:1.32-6.83). This association was also observed in individuals with frailty only (OR=2.11,95%CI:1.04-4.27) but not for patients with cognitive impairment only((OR=1.11,95%CI:0.43-2.85).

CONCLUSION: Our study suggested that hospitalized Chinese older adults with cognitive frailty were independently associated with falls. Early screening frailty and cognitive impairment were significant for older patients by clinicians, and corresponding interventions, exercise training and nutritional programs, should be implemented to prevent falls.

PMID:34545919 | DOI:10.1007/s12603-021-1670-y

Am J Surg Pathol. 2021 Sep 21. doi: 10.1097/PAS.0000000000001810. Online ahead of print.

ABSTRACT

The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the World Health Organization 2020 Classification specifies that loss of Pten, Pax2, or mismatch repair proteins are desirable diagnostic criteria. Other markers, most notably β-catenin and Arid1a, are also aberrantly expressed in some AH/EIN. However, the performance of some markers individually-and more importantly as a group-has not been rigorously explored, raising questions as to which marker(s) or combination(s) is the most effective in practice. Formalin-fixed paraffin-embedded tissue sections from AH/EIN cases (n=111) were analyzed by immunohistochemistry for 6 markers: Pax2, Pten, Mlh1, β-catenin, Arid1a, and p53. Aberrant expression was tabulated for each case and marker. An additional set of normal endometria (n=79) was also analyzed to define optimal diagnostic criteria for marker aberrance. The performance characteristics of each marker, the entire panel, and subsets thereof were quantitatively and statistically analyzed. In order of number of cases detected, the most frequently aberrant markers in AH/EIN were Pax2 (81.1% of cases), Pten (50.5%), β-catenin (47.7%), Arid1a (7.2%), Mlh1 (4.5%), and p53 (2.7%). The majority of cases showed aberrant expression of ≥2 markers. All 6 markers together identified 92.8% of cases. Arid1a, Mlh1, and p53 were robust and readily scored markers, but all cases showing aberrant expression of these 3 markers were also detected by Pax2, Pten, or β-catenin. A focused panel of only 3 markers (Pax2, Pten, and β-catenin) showed optimal performance characteristics as a diagnostic adjunct in the histopathologic diagnosis of AH/EIN. Use of this panel is practicable and robust, with at least 1 of the 3 markers being aberrant in 92.8% of AH/EIN.

PMID:34545858 | DOI:10.1097/PAS.0000000000001810

J Pediatr Orthop B. 2021 Sep 17. doi: 10.1097/BPB.0000000000000916. Online ahead of print.

ABSTRACT

During the coronavirus disease 2019 (COVID-19) pandemic, many aspects of healthcare have been hindered. The primary aim of this study was to identify what the impact of COVID-19 was on the delivery of outpatient care for children with congenital talipes equinovarus deformity (CTEV) at a large tertiary hospital in the UK. This study reviewed the patients who commenced their Ponseti treatment between March and September 2020, representing the cohort who received hands-on care during the first wave of the COVID-19 pandemic. Equivalent 6-month periods were searched in 2019 and 2018 as control cohorts. This study included a total of 45 children (72 affected feet) presenting for treatment of clubfoot. Twenty-three babies were seen with CTEV in 2020. For the same time period in 2018 and 2019, 11 babies were treated each year. The distance commuted to by families was higher in 2020 compared to 2019 and 2018, although the difference did not reach statistical significance (P = 0.301). Treatment with Ponseti casting was commenced at a mean age of 52 days, with no statistically significant differences between cohorts (P = 0.758). Using strict precautions, the Ponseti service at a large tertiary hospital in the UK grew in size and successfully provided treatment for children presenting with CTEV during the first wave of the COVID-19 pandemic. This study has shown that with careful protocols in place, children with CTEV can be treated successfully during times of pandemic, thereby reducing the post-pandemic burden of older children requiring treatment.

PMID:34545852 | DOI:10.1097/BPB.0000000000000916