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Nevin Manimala Statistics

CT predictors of sub-centimeter occult lymph node metastases in oral cavity squamous cell carcinoma: A case-control study

Neuroradiol J. 2023 Dec 26:19714009231224447. doi: 10.1177/19714009231224447. Online ahead of print.

ABSTRACT

BACKGROUND: For patients with oral cavity squamous cell carcinoma (OCSCC) without evidence of nodal metastasis (cN0) on pre-operative evaluation, there are no clear guidelines who should undergo elective neck dissection (END) versus clinical surveillance.

OBJECTIVE: To identify CT imaging characteristics of sub-centimeter lymph nodes that would help predict the likelihood of nodal metastases on pathology.

METHODS: Retrospective review of cN0 OCSCC patients at a tertiary academic medical center was performed. Inclusion criteria included elective neck dissection, pre-operative CT imaging and presence of metastatic disease within lymph nodes. Control group consisted of patients without nodal metastases on pathology. CT features that were evaluated included asymmetric size, disrupted fatty hilum, asymmetric number, presence of cortical nodule, cortical nodule size, and round/oval shape. We evaluated the associations between CT LN features and the presence of metastases using multi-level mixed-effects logistic regression models. Model evaluation was performed using 5-fold cross-validation. The positive predictive value (PPV) and negative predictive value (NPV) were calculated.

RESULTS: 26 patients in each study and control groups were included. Three-level mixed-effects logistic regression models indicated round/oval shape (OR = 1.39, p = .01), asymmetric number (OR = 7.20, p = .005), and disrupted fatty hilum (OR = 3.31, p = .04) to be independently predictive in a 3-variable model with sensitivity = 38.0%, specificity = 92.0%, and PPV = 93.8%.

CONCLUSIONS: In cN0 OCSCC patients undergoing END, round/oval shape, asymmetric number, and disrupted fatty hilum of lymph nodes on pre-operative CT imaging are novel and highly predictive of occult nodal disease.

PMID:38148295 | DOI:10.1177/19714009231224447

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The Impact of a Novel Musculoskeletal Consult Service in an Inpatient Rehabilitation Facility: A Descriptive Analysis

PM R. 2023 Dec 26. doi: 10.1002/pmrj.13118. Online ahead of print.

ABSTRACT

INTRODUCTION: Musculoskeletal (MSK) pathologies significantly impact the rehabilitation course for patients admitted to an inpatient rehabilitation facility (IRF). The impact of a specialized inpatient MSK consult service has not been previously evaluated.

OBJECTIVE: To assess the demographics, pathologies, and impact on pain scores of patients who were evaluated by a specialized MSK consult service.

DESIGN: Retrospective descriptive analysis of patients at an IRF who were evaluated by the MSK consult service.

SETTING: Academic IRF.

PATIENTS (OR PARTICIPANTS): 230 patients evaluated by the MSK consult service over 4.5 years.

INTERVENTIONS: MSK consult service composed of sports medicine fellowship-trained physiatrists who utilize history, physical examination, point-of-care ultrasound and specialized MSK knowledge to assess and address MSK barriers to functional improvement.

MAIN OUTCOME MEASURE(S): Primary rehabilitation diagnosis, length of stay, discharge destination, reason for consult, MSK diagnosis, need for injection, change in numerical pain rating scale (NPRS) pain scores, change in Functional Independence Measures (FIM).

RESULTS: 230 consults met inclusion criteria for analysis. The most common complaints were shoulder pain (47%), knee pain (30%), and hip/groin pain (10.4%). The MSK consult service made 82 different musculoskeletal and neuromuscular diagnoses. The most common primary rehabilitation diagnosis was stroke (28.3%). Injections were performed in 44.3% of consults, with an average reduction in NPRS pain score of 2.3 (SD 1.9) and a statistically significant reduction in average NPRS pain scores in patients who underwent injections compared to those who did not (p < 0.0001).

CONCLUSIONS: This study is the first to examine the use of an innovative inpatient MSK physiatry consult service in an IRF. This promising consult service can play a pivotal role in patient care by reducing functionally limiting musculoskeletal pain to allow for better toleration of therapies and to optimize functional gains.

PMID:38148275 | DOI:10.1002/pmrj.13118

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Do diverse wheat genotypes unleash their biochemical arsenal differentially to conquer cold stress? A comprehensive study in the Western Himalayas

Physiol Plant. 2023 Nov-Dec;175(6):e14069. doi: 10.1111/ppl.14069.

ABSTRACT

Wheat is one of the most important cereal crops in the world. Cold stress is a major constraint in production of wheat grown in cold climate regions. In this study, we conducted a comprehensive assessment of cold stress tolerance in wheat genotypes through field screening, cell membrane stability through electrolyte leakage assay and biochemical profiling. A core set comprising 4560 genotypes was evaluated for two years (2021-2022), revealing substantial genetic variation for cold stress tolerance. Most genotypes exhibited moderate tolerance, while a smaller proportion showed susceptibility to cold stress. Based on the cold screening data in the field, a mini-core set of 350 genotypes was selected for membrane stability analysis using electrical conductivity assays. Significant differences were observed in membrane stability among the genotypes, indicating the presence of genetic variation for this trait. Furthermore, a mini-core set was narrowed down to 50 diverse candidate genotypes that were subsequently profiled for various biochemicals, including reactive oxygen species (ROS) like lipid peroxidation (MDA) and hydrogen peroxide (H2 02 ), osmoprotectant (proline) and enzymatic antioxidants including ascorbate peroxidase (APX), superoxide dismutase (SOD), guaiacol peroxidase (GPX), and catalase (CAT). Correlation analysis of the biochemicals revealed negative associations between antioxidants and reactive oxygen species (ROS), highlighting their role in mitigating oxidative damage under cold stress. This study enhances our understanding of the physiological and biochemical mechanisms underlying cold stress tolerance in wheat. The identified genotypes with superior cold stress tolerance can serve as valuable genetic resources for wheat breeding.

PMID:38148247 | DOI:10.1111/ppl.14069

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Optimizing foliar N-fertilization in sugarcane depends on plant genotype and nitrogen concentration

Physiol Plant. 2023 Nov-Dec;175(6):e14085. doi: 10.1111/ppl.14085.

ABSTRACT

Foliar N-fertilization (FNf) has emerged as a promising approach to synchronize plant nitrogen (N) demands and application timing, reducing the N losses to the environment associated with traditional soil-based fertilization methods. However, limited information exists regarding the effectiveness of FNf in sugarcane. This study aimed to optimize FNf in sugarcane by evaluating N-fertilizer recovery by the plant (NRP) and assessing potential toxicity effects. Four sugarcane genotypes were subjected to FNf using 15 N-urea at five nitrogen concentrations. NRP was assessed at five time points for roots, stalk, old leaves, 15 N-urea-fertilized leaves (15 NL), and unexpanded leaves (UEL). Leaf scorching, indicating FNf toxicity, was analyzed using morpho-anatomical and histochemical techniques. The results showed that FNf promoted high NRP, with an average recovery of 62.3%. Surprisingly, the redistribution of 15 N-urea did not follow the nitrogen uptake rate by sugarcane leaves, with an average of 41.3% of the total-NRP. The stalk emerged as the primary sink for 15 N-urea, followed by the UEL. Genotypes differed in the leaf scorching intensity, which increased with higher concentration of 15 N-urea. Genotypes also differed in the 15 N-urea uptake rate, down-regulated by the N content in the 15 NL. These findings emphasize that by carefully choosing the appropriate genotype and nitrogen concentration, FNf can significantly enhance N-fertilizer uptake, resulting in potential environmental and economic benefits.

PMID:38148209 | DOI:10.1111/ppl.14085

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Single-shot diffusion trace-weighted MR spectroscopy: Comparison with unipolar and bipolar diffusion-weighted point-resolved spectroscopy

NMR Biomed. 2023 Dec 26:e5090. doi: 10.1002/nbm.5090. Online ahead of print.

ABSTRACT

This study demonstrates the feasibility and performance of the point-resolved spectroscopy (PRESS)-based, single-shot diffusion trace-weighted sequence in quantifying the trace apparent diffusion coefficient (ADC) in phantom and in vivo using a 3-T MRI/MRS scanner. The single-shot diffusion trace-weighted PRESS sequence was implemented and compared with conventional diffusion-weighted (DW)-PRESS variants using bipolar and unipolar diffusion-sensitizing gradients. Nine phantom datasets were acquired using each sequence, and seven volunteers were scanned in three different brain regions to determine the range and variability of trace ADC values, and to allow a comparison of trace ADCs among the sequences. This sequence results in a comparatively stable range of trace ADC values that are statistically significantly higher than those produced from unipolar and bipolar DW-PRESS sequences. Only total n-acetylaspartate, total creatine, and total choline were reliably estimated in all sequences with Cramér-Rao lower bounds of, at most, 20%. The larger trace ADCs from the single-shot sequences are probably attributable to the shorter diffusion time relative to the other sequences. Overall, this study presents the first demonstration of the single-shot diffusion trace-weighted sequence in a clinical scanner at 3 T. The results show excellent agreement of phantom trace ADCs computed with all sequences, and in vivo ADCs agree well with the expected differences between gray and white matter. The diffusion trace-weighted sequence could provide an estimate of the trace ADC in a shorter scan time (by nearly a factor of 3) compared with conventional DW-PRESS approaches that require three separate orthogonal directions.

PMID:38148181 | DOI:10.1002/nbm.5090

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Short-term and long-term outcomes of submucosal dissection for residual or recurrent colorectal tumors after endoscopic resection: Analysis of a multicenter prospective study

Dig Endosc. 2023 Dec 26. doi: 10.1111/den.14752. Online ahead of print.

ABSTRACT

BACKGROUND: We previously demonstrated that a favorable long-term prognosis indicated that endoscopic submucosal dissection (ESD) could be the standard treatment for large colorectal epithelial neoplasms, but the usefulness of ESD for local residual or recurrent tumors with submucosal fibrosis has not been fully demonstrated. The aim of the present study was to assess the usefulness of ESD for local residual or recurrent colorectal tumors.

METHODS: We conducted a nationwide multicenter prospective study to evaluate the outcomes of ESD for colorectal tumors. In this post-hoc analysis, a total of 54 local residual or recurrent colorectal tumors in 54 patients were included, and we analyzed the short-term and long-term outcomes of ESD for these lesions.

RESULTS: The median size of the lesions was 16.0 (IQR;11-25) mm. ESD was completed in 53 cases (98.1%) with a median procedure time of 65.0 min, but it was discontinued in one case due to submucosal cancer invasion. En-bloc resection was achieved in 52 cases (96.3%), while R0 resection was achieved in 45 cases (83.3%). Intraoperative perforation was observed in 4 cases (7.4%) and delayed perforation in 1 case (1.9%), but all cases could be managed conservatively. Delayed bleeding was not observed. There were no significant differences in short-term outcomes between the rectal and colonic lesions. There was no recurrence of the tumor during the median follow-up period of 60 months (IQR 50-64).

CONCLUSION: An analysis of our multicenter prospective study suggests that ESD is an effective salvage management for local residual or recurrent colorectal lesions.

PMID:38148178 | DOI:10.1111/den.14752

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Hypertensive disorders of pregnancy and cardiovascular disease risk: a Mendelian randomisation study

Heart. 2023 Dec 26:heartjnl-2023-323490. doi: 10.1136/heartjnl-2023-323490. Online ahead of print.

ABSTRACT

OBJECTIVE: Observational studies show that hypertensive disorders of pregnancy (HDPs) are related to unfavourable maternal cardiovascular disease (CVD) risk profiles later in life. We investigated whether genetic liability to pre-eclampsia/eclampsia and gestational hypertension is associated with CVD risk factors and occurrence of CVD events.

METHODS: We obtained genetic associations with HDPs from a genome-wide association study and used individual participant data from the UK Biobank to obtain genetic associations with CVD risk factors and CVD events (defined as myocardial infarction or stroke). In our primary analysis, we applied Mendelian randomisation using inverse-variance weighted regression analysis in ever pregnant women. In sensitivity analyses, we studied men and nulligravidae to investigate genetic liability to HDPs and CVD risk without the ability to experience the underlying phenotype.

RESULTS: Our primary analysis included 221 155 ever pregnant women (mean age 56.8 (SD 7.9) years) with available genetic data. ORs for CVD were 1.20 (1.02 to 1.41) and 1.24 (1.12 to 1.38) per unit increase in the log odds of genetic liability to pre-eclampsia/eclampsia and gestational hypertension, respectively. Furthermore, genetic liability to HDPs was associated with higher levels of systolic and diastolic blood pressure and younger age at hypertension diagnosis. Sensitivity analyses revealed no statistically significant differences when comparing the findings with those of nulligravidae and men.

CONCLUSIONS: Genetic liability to HDPs is associated with higher CVD risk, lower blood pressure levels and earlier hypertension diagnosis. Our study suggests similar findings in ever pregnant women, nulligravidae and men, implying biological mechanisms relating to HDPs are causally related to CVD risk.

PMID:38148158 | DOI:10.1136/heartjnl-2023-323490

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Filamin A heart valve disease as a genetic cause of inherited bicuspid and tricuspid aortic valve disease

Heart. 2023 Dec 26:heartjnl-2023-323491. doi: 10.1136/heartjnl-2023-323491. Online ahead of print.

ABSTRACT

OBJECTIVE: Variants in the FLNA gene have been associated with mitral valve dystrophy (MVD), and even polyvalvular disease has been reported. This study aimed to analyse the aortic valve and root involvement in FLNA-MVD families and its impact on outcomes.

METHODS: 262 subjects (37 (18-53) years, 140 male, 79 carriers: FLNA+) from 4 FLNA-MVD families were included. Echocardiography was performed in 185 patients and histological analysis in 3 explanted aortic valves. The outcomes were defined as aortic valve surgery or all-cause mortality.

RESULTS: Aortic valve alterations were found in 58% of FLNA+ compared with 6% of FLNA– (p<0.001). 9 (13.4%) FLNA+ had bicuspid aortic valve compared with 4 (3.4%) FLNA– (p=0.03). Overall, the transvalvular mean gradient was slightly increased in FLNA+ (4.8 (4.1-6.1) vs 4.0 (2.9-4.9) mm Hg, p=0.02). The sinuses of Valsalva and sinotubular junction diameters were enlarged in FLNA+ subjects (all p<0.05). 8 FLNA+ patients underwent aortic valve surgery (0 in relatives; p<0.001). Myxomatous remodelling with an infiltration of immune cells was observed. Overall survival was similar between FLNA+ versus FLNA– subjects (86±5% vs 85±6%, p=0.36). There was no statistical evidence for an interaction between genetic status and sex (p=0.15), but the survival tended to be impaired in FLNA+ men (p=0.06) whereas not in women (p=0.71).

CONCLUSION: The patients with FLNA variants present frequent aortic valve disease and worse outcomes. Bicuspid aortic valve is more frequent in patients carrying the FLNA-MVD variants. These unique features should be factored into the management of patients with dystrophic and/or bicuspid aortic valve.

PMID:38148157 | DOI:10.1136/heartjnl-2023-323491

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Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS)

Thorax. 2023 Dec 26:thorax-2023-220292. doi: 10.1136/thorax-2023-220292. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammatory subphenotypes have been identified in acute respiratory distress syndrome (ARDS). Hyperferritinaemia in sepsis is associated with hyperinflammation, worse clinical outcomes, and may predict benefit with immunomodulation. Our aim was to determine if raised ferritin identified a subphenotype in patients with ARDS.

METHODS: Baseline plasma ferritin concentrations were measured in patients with ARDS from two randomised controlled trials of simvastatin (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction-2 (HARP-2); discovery cohort, UK) and neuromuscular blockade (ROSE; validation cohort, USA). Results were analysed using a logistic regression model with restricted cubic splines, to determine the ferritin threshold associated with 28-day mortality.

RESULTS: Ferritin was measured in 511 patients from HARP-2 (95% of patients enrolled) and 847 patients (84% of patients enrolled) from ROSE. Ferritin was consistently associated with 28-day mortality in both studies and following a meta-analysis, a log-fold increase in ferritin was associated with an OR 1.71 (95% CI 1.01 to 2.90) for 28-day mortality. Patients with ferritin >1380 ng/mL (HARP-2 28%, ROSE 24%) had a significantly higher 28-day mortality and fewer ventilator-free days in both studies. Mediation analysis, including confounders (acute physiology and chronic health evaluation-II score and ARDS aetiology) demonstrated a statistically significant contribution of interleukin (IL)-18 as an intermediate pathway between ferritin and mortality.

CONCLUSIONS: Ferritin is a clinically useful biomarker in ARDS and is associated with worse patient outcomes. These results provide support for prospective interventional trials of immunomodulatory agents targeting IL-18 in this hyperferritinaemic subgroup of patients with ARDS.

PMID:38148147 | DOI:10.1136/thorax-2023-220292

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Gallic acid triphenylphosphonium derivatives TPP+-C10 and TPP+-C12 inhibit mitochondrial function in Candida albicans exerting antifungal and antibiofilm effects

J Appl Microbiol. 2023 Dec 26:lxad316. doi: 10.1093/jambio/lxad316. Online ahead of print.

ABSTRACT

AIMS: To evaluate the antifungal and antibiofilm activity of gallic acid derivatives TPP+-C10 and TPP+-C12 and their effects on mitochondrial function on two C. albicans reference strains (ATCC 90029 and ATCC 10231).

METHODS AND RESULTS: First, we determined minimal inhibitory concentration using a microdilution assay. Both compounds exerted antifungal effects, and their minimal inhibitory concentrations (MICs) ranged from 3.9 to 13 μM, with no statistically significant differences between them (P > 0.05, t-test). These concentrations served as references for following assays. Subsequently, we measured oxygen consumption with a Clark electrode. Our observations revealed that both drugs inhibited oxygen consumption in both strains with TPP+-C12 exerting a more pronounced inhibitory effect. We then employed flow cytometry with TMRE as a probe to assess mitochondrial membrane potential. For each strain assayed, the compounds induced a decay in transmembrane potential by 75% to 90% compared to the control condition (P < 0.05, ANOVA). Then, we measured ATP levels using a commercial kit. TPP+-C12 showed a 50% decrease of ATP content (P < 0.05 ANOVA), while TPP+-C10 exhibited a less pronounced effect. Finally, we assessed the antibiofilm effect using the MTT reduction assay. Both compounds were effective, but TPP+-C12 displayed a greater potency, requiring a lower concentration to inhibit 50% of biofilms viability (P < 0.05, t-test).

CONCLUSIONS: Derivatives of gallic acid linked to a TPP+ group exert antifungal and antibiofilm activity through impairment of mitochondrial function in C. albicans.

PMID:38148145 | DOI:10.1093/jambio/lxad316