Category: Nevin Manimala

JAMA Netw Open. 2022 May 2;5(5):e2210331. doi: 10.1001/jamanetworkopen.2022.10331.

ABSTRACT

IMPORTANCE: Guiding treatment decisions for women with ductal carcinoma in situ (DCIS) requires understanding patient preferences and the influence of preoperative magnetic resonance imaging (MRI) and surgeon recommendation.

OBJECTIVE: To identify factors associated with surgery preference and surgery receipt among a prospective cohort of women with newly diagnosed DCIS.

DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted at 75 participating institutions, including community practices and academic centers, across the US between March 25, 2015, and April 27, 2016. Data were analyzed from August 2 to September 24, 2021. This was an ancillary study of the ECOG-ACRIN Cancer Research Group (E4112). Women with recently diagnosed unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. Participants who had documented surgery and completed the baseline patient-reported outcome questionnaires were included in this substudy.

EXPOSURES: Women received preoperative MRI and surgeon consultation and then underwent wide local excision or mastectomy. Participants will be followed up for recurrence and overall survival for 10 years from the date of surgery.

MAIN OUTCOMES AND MEASURES: Patient-reported outcome questionnaires assessed treatment goals and concerns and surgery preference before MRI and after MRI and surgeon consultation.

RESULTS: Of the 368 participants enrolled 316 (86%) were included in this substudy (median [range] age, 59.5 [34-87] years; 45 women [14%] were Black; 245 [78%] were White; and 26 [8%] were of other race). Pre-MRI, age (odds ratio [OR] per 5-year increment, 0.45; 95% CI, 0.26-0.80; P = .007) and the importance of keeping one’s breast (OR, 0.48; 95% CI, 0.31-0.72; P < .001) vs removal of the breast for peace of mind (OR, 1.35; 95% CI, 1.04-1.76; P = .03) were associated with surgery preference for mastectomy. After MRI and surgeon consultation, MRI upstaging (48 of 316 [15%]) was associated with patient preference for mastectomy (OR, 8.09; 95% CI, 2.51-26.06; P < .001). The 2 variables with the highest ORs for initial receipt of mastectomy were MRI upstaging (OR, 12.08; 95% CI, 4.34-33.61; P < .001) and surgeon recommendation (OR, 4.85; 95% CI, 1.99-11.83; P < .001).

CONCLUSIONS AND RELEVANCE: In this cohort study, change in patient preference for DCIS surgery and surgery received were responsive to MRI results and surgeon recommendation. These data highlight the importance of ensuring adequate information and ongoing communication about the clinical significance of MRI findings and the benefits and risks of available treatment options.

PMID:35536580 | DOI:10.1001/jamanetworkopen.2022.10331

Mol Divers. 2022 May 10. doi: 10.1007/s11030-022-10437-1. Online ahead of print.

ABSTRACT

Tea (Camellia sinensis L.) is considered as to be one of the most consumed beverages globally and a reservoir of phytochemicals with immense health benefits. Despite numerous advantages, tea compounds lack a robust multi-disease target study. In this work, we presented a unique in silico approach consisting of molecular docking, multivariate statistics, pharmacophore analysis, and network pharmacology approaches. Eight tea phytochemicals were identified through literature mining, namely gallic acid, catechin, epigallocatechin gallate, epicatechin, epicatechin gallate (ECG), quercetin, kaempferol, and ellagic acid, based on their richness in tea leaves. Further, exploration of databases revealed 30 target proteins related to the pharmacological properties of tea compounds and multiple associated diseases. Molecular docking experiment with eight tea compounds and all 30 proteins revealed that except gallic acid all other seven phytochemicals had potential inhibitory activities against these targets. The docking experiment was validated by comparing the binding affinities (Kcal mol^-1) of the compounds with known drug molecules for the respective proteins. Further, with the aid of the application of statistical tools (principal component analysis and clustering), we identified two major clusters of phytochemicals based on their chemical properties and docking scores (Kcal mol^-1). Pharmacophore analysis of these clusters revealed the functional descriptors of phytochemicals, related to the ligand-protein docking interactions. Tripartite network was constructed based on the docking scores, and it consisted of seven tea phytochemicals (gallic acid was excluded) targeting five proteins and ten associated diseases. Epicatechin gallate (ECG)-hepatocyte growth factor receptor (PDB id 1FYR) complex was found to be highest in docking performance (10 kcal mol^-1). Finally, molecular dynamic simulation showed that ECG-1FYR could make a stable complex in the near-native physiological condition.

PMID:35536529 | DOI:10.1007/s11030-022-10437-1

Int J Hematol. 2022 May 10. doi: 10.1007/s12185-022-03368-y. Online ahead of print.

ABSTRACT

We compared the outcomes of autologous stem cell transplantation (auto-SCT) with those of allogeneic stem cell transplantation (allo-SCT) from a human leukocyte antigen-matched related donor in patients with Philadelphia chromosome-negative B-lineage acute lymphoblastic leukemia (ALL). Newly diagnosed patients who underwent allo-SCT (n = 486) or auto-SCT (n = 99) after achieving first complete remission (CR) were included. Propensity score matching (PS) and an inverse probability of the treatment weighting (IPTW) analysis were applied to compensate for imbalances in baseline characteristics. The 5 years rates of overall survival (OS) among those in the PS-matched cohorts were 57% [95% confidence interval (CI) 46-67%] for those who received allo-SCT and 44% (95% CI 33-54%) for those who received auto-SCT. Multivariable, propensity score-matched, and IPTW analyses all revealed no statistically significant differences in OS between the two groups [hazard ratios (HR) 0.81, 95% CI 0.53-1.27, p = 0.36; HR 0.84, 95% CI 0.40-1.78, p = 0.65; HR 0.71, 95% CI 0.25-2.02, p = 0.53, respectively]. Prospective trials that include autologous transplantation as a treatment option are needed to examine the potential of autologous transplantation.

PMID:35536509 | DOI:10.1007/s12185-022-03368-y

Insights Imaging. 2022 May 10;13(1):87. doi: 10.1186/s13244-022-01227-2.

ABSTRACT

BACKGROUND: The application of deep learning has allowed significant progress in medical imaging. However, few studies have focused on the diagnosis of benign and malignant spinal tumors using medical imaging and age information at the patient level. This study proposes a multi-model weighted fusion framework (WFF) for benign and malignant diagnosis of spinal tumors based on magnetic resonance imaging (MRI) images and age information.

METHODS: The proposed WFF included a tumor detection model, sequence classification model, and age information statistic module based on sagittal MRI sequences obtained from 585 patients with spinal tumors (270 benign, 315 malignant) between January 2006 and December 2019 from the cooperative hospital. The experimental results of the WFF were compared with those of one radiologist (D1) and two spine surgeons (D2 and D3).

RESULTS: In the case of reference age information, the accuracy (ACC) (0.821) of WFF was higher than three doctors’ ACC (D1: 0.686; D2: 0.736; D3: 0.636). Without age information, the ACC (0.800) of the WFF was also higher than that of the three doctors (D1: 0.750; D2: 0.664; D3:0.614).

CONCLUSIONS: The proposed WFF is effective in the diagnosis of benign and malignant spinal tumors with complex histological types on MRI.

PMID:35536493 | DOI:10.1186/s13244-022-01227-2

Sports Med Open. 2022 May 10;8(1):64. doi: 10.1186/s40798-022-00453-8.

ABSTRACT

BACKGROUND: Physical exercise has favorable effects on the structure of gut microbiota and metabolite production in sedentary subjects. However, little is known whether adjustments in an athletic program impact overall changes of gut microbiome in high-level athletes. We therefore characterized fecal microbiota and serum metabolites in response to a 7-week, high-intensity training program and consumption of probiotic Bryndza cheese.

METHODS: Fecal and blood samples and training logs were collected from young competitive male (n = 17) and female (n = 7) swimmers. Fecal microbiota were categorized using specific primers targeting the V1-V3 region of 16S rDNA, and serum metabolites were characterized by NMR-spectroscopic analysis and by multivariate statistical analysis, Spearman rank correlations, and Random Forest models.

RESULTS: We found higher α-diversity, represented by the Shannon index value (HITB-pre 5.9 [± 0.4]; HITB-post 6.4 [± 0.4], p = 0.007), (HIT-pre 5.5 [± 0.6]; HIT-post 5.9 [± 0.6], p = 0.015), after the end of the training program in both groups independently of Bryndza cheese consumption. However, Lactococcus spp. increased in both groups, with a higher effect in the Bryndza cheese consumers (HITB-pre 0.0021 [± 0.0055]; HITB-post 0.0268 [± 0.0542], p = 0.008), (HIT-pre 0.0014 [± 0.0036]; HIT-post 0.0068 [± 0.0095], p = 0.046). Concomitant with the increase of high-intensity exercise and the resulting increase of anaerobic metabolism proportion, pyruvate (p[HITB] = 0.003; p[HIT] = 0.000) and lactate (p[HITB] = 0.000; p[HIT] = 0.030) increased, whereas acetate (p[HITB] = 0.000; p[HIT] = 0.002) and butyrate (p[HITB] = 0.091; p[HIT] = 0.019) significantly decreased.

CONCLUSIONS: Together, these data demonstrate a significant effect of high-intensity training (HIT) on both gut microbiota composition and serum energy metabolites. Thus, the combination of intensive athletic training with the use of natural probiotics is beneficial because of the increase in the relative abundance of lactic acid bacteria.

PMID:35536489 | DOI:10.1186/s40798-022-00453-8

J Am Geriatr Soc. 2022 May 10. doi: 10.1111/jgs.17810. Online ahead of print.

ABSTRACT

BACKGROUND: Age-related morbidities and frailty are associated with impaired blood pressure (BP) and heart rate (HR) recovery after standing. Here we investigate how multimorbidity affects cerebral and peripheral hemodynamics during standing in a large sample of older patients.

METHODS: Patients were recruited from a national Falls and Syncope Unit. They underwent an active stand test (5-10 min lying +3 min standing) with monitoring of continuous BP, HR, total peripheral resistance (TPR), stroke volume (SV), and a near-infrared spectroscopy (NIRS) derived cerebral tissue saturation index (TSI). A multimorbidity count was derived from a 26-item list of conditions. Features derived from the signals included: nadir, overshoot, value at 30 s, steady-state and recovery rate. Robust linear regression was used to assess the association between multimorbidity, TSI and peripheral hemodynamics while correcting for covariates. A p-value <0.05 was considered statistically significant.

RESULTS: Multimorbidity was associated with poorer recovery of TSI at 30 s after standing (β: -0.15, CI:[-0.25-0.06], p = 0.009) independent of all peripheral hemodynamics. Impaired diastolic BP (DBP) recovery at 30s (β:-1.34, CI:[-2.29-0.40], p = 0.032), DBP steady-state (β:-1.18, CI:[-2.04-0.32], p = 0.032), TPR overshoot-to-nadir difference (β:-0.041, CI:[-0.070-0.013], p = 0.045), and SV at 30s (β:1.30, CI:[0.45 2.15], p = 0.027) were also associated with increasing multimorbidity. After sex stratification, only females demonstrated impaired TSI with multimorbidity at overshoot (β: -0.19, CI: [-0.32 -0.07], p = 0.009), 30 s (β: -0.22 [-0.35-0.10], p = 0.005) and steady-state (β: -0.20, CI:[-0.35-0.04], p = 0.023), independent of peripheral hemodynamics.

CONCLUSIONS: Transient cerebral oxygenation and peripheral hemodynamic responses are impaired with multimorbidity (frailty) in older patients, particularly in females. This study demonstrates the feasibility of using NIRS in this clinical context and may inform the development of clinical management strategies targeting both cerebral oxygenation and blood pressure impairments in patients with faints and falls.

PMID:35535653 | DOI:10.1111/jgs.17810

Soft Matter. 2022 May 10. doi: 10.1039/d1sm01765a. Online ahead of print.

ABSTRACT

Two different tensions can be defined for a fluid membrane: the internal tension, γ, conjugated to the real membrane area in the Hamiltonian, and the frame tension, τ, conjugated to the projected (or frame) area. According to the standard statistical description of a membrane, the fluctuation spectrum is governed by γ. However, using rotational invariance arguments, several studies argued that the fluctuation spectrum must be governed by the frame tension τ instead. These studies disagree on the origin of the result obtained with the standard description yet: either a miscounting of configurations, quantified with the integration measure, or the use of a quadratic approximation of the Helfrich Hamiltonian. Analyzing the simplest case of a one-dimensional membrane, for which the arc length offers a natural parametrization, we give a new proof that the fluctuations are driven by τ, and show that the origin of the issue with the standard description is a miscounting of membrane configurations. The origin itself of this miscounting depends on the thermodynamic ensemble in which calculations are made.

PMID:35535647 | DOI:10.1039/d1sm01765a

Soft Matter. 2022 May 10. doi: 10.1039/d2sm00258b. Online ahead of print.

ABSTRACT

Biofilm formation is the most successful survival strategy for bacterial communities. In the biofilm lifestyle, bacteria embed themselves in a self-secreted matrix of extracellular polymeric substances (EPS), which acts as a shield against mechanical and chemical insults. When ambient flow is present, this viscoelastic scaffold can take a streamlined shape, forming biofilm filaments suspended in flow, called streamers. Streamers significantly disrupt the fluid flow by causing rapid clogging and affect transport in aquatic environments. Despite their relevance, the structural and rheological characterization of biofilm streamers is still at an early stage. In this work, we present a microfluidic platform that allows the reproducible growth of biofilm streamers in controlled physico-chemical conditions and the characterization of their biochemical composition, morphology, and rheology in situ. We employed isolated micropillars as nucleation sites for the growth of single biofilm streamers under the continuous flow of a diluted bacterial suspension. By combining fluorescent staining of the EPS components and epifluorescence microscopy, we were able to characterize the biochemical composition and morphology of the streamers. Additionally, we optimized a protocol to perform hydrodynamic stress tests in situ, by inducing controlled variations of the fluid shear stress exerted on the streamers by the flow. Thus, the reproducibility of the formation process and the testing protocol make it possible to perform several consistent experimental replicates that provide statistically significant information. By allowing the systematic investigation of the role of biochemical composition on the structure and rheology of streamers, this platform will advance our understanding of biofilm formation.

PMID:35535650 | DOI:10.1039/d2sm00258b

Dermatol Ther. 2022 May 10:e15573. doi: 10.1111/dth.15573. Online ahead of print.

ABSTRACT

BACKGROUND: During the SARS-COV-2 pandemic, using face masks became mandatory in many countries. Although evidence suggests that masks can exacerbate several inflammatory skin diseases, few studies focus on their real impact on eczema localized to the face in atopic dermatitis (AD) patients.

OBJECTIVE: The aim of this study is to evaluate facial eczema prevalence during pandemic and its psychological impact in AD patients pre-assessed for systemic treatment and/or in therapy with dupilumab.

METHODS: This study includes 71 patients affected by moderate-severe AD, treated with dupilumab at SCDU of Dermatology in Novara, Italy. We calculated the number of subjects with facial involvement in pre- and post-pandemic periods and the related localization trend. We evaluated, in the two groups, clinical and psychological indicators recorded at each visit and the score modifications during the observational period.

RESULTS: No statistically significant differences were observed in facial eczema prevalence, between pre- and post-pandemic periods (p = 0.7618) and in facial eczema remission among the two groups (p = 0.1903). In post-pandemic period, psychological scores were significantly lower (DLQI and HADS respectively with p <0.0001 and p = 0.0025) and the reduction in EASI score during observational period was significantly greater (p = 0.0001).

CONCLUSIONS: Our analysis revealed a potential protective effect of masks on face eczema, suggesting that they could enhance dupilumab efficacy. Face masks, covering sensitive areas, can positively contribute to mental distress in patients with facial eczema, and being associated with a lower allergic diseases incidence may sustain dupilumab in reducing AD severity. This article is protected by copyright. All rights reserved.

PMID:35535633 | DOI:10.1111/dth.15573

J Am Heart Assoc. 2022 May 10:e023010. doi: 10.1161/JAHA.121.023010. Online ahead of print.

ABSTRACT

Background Experiments measuring the contractile properties of human myocardium are important for translational research but complicated by the logistical difficulties of acquiring specimens. Accordingly, many groups perform contractile assays using samples that are acquired from patients at one institution and shipped to another institution for experiments. This necessitates freezing the samples and performing subsequent assays using chemically permeabilized preparations. It is unknown how prior freezing affects the contractile function of these preparations. Methods and Results To examine the effects of freezing we measured the contractile function of never-frozen and previously frozen myocardial samples. Samples of left ventricular tissue were obtained from 7 patients who were having a ventricular assist device implanted. Half of each sample was chemically permeabilized and used immediately for contractile assays. The other half of the sample was snap frozen in liquid nitrogen and maintained at -180 °C for at least 6 months before being thawed and tested in a second series of experiments. Maximum isometric force measured in pCa 4.5 solution, passive force measured in pCa 9.0 solution, and Hill coefficients were not influenced by prior freezing (P=0.07, P=0.14, and P=0.27 respectively). pCa₅₀ in never-frozen samples (6.11±0.04) was statistically greater (P<0.001) than that measured after prior freezing (5.99±0.04) but the magnitude of the effect was only ≈0.1 pCa units. Conclusions We conclude that prior freezing has minimal impact on the contractile properties that can be measured using chemically permeabilized human myocardium.

PMID:35535623 | DOI:10.1161/JAHA.121.023010