Nevin Manimala

Pathol Res Pract. 2021 Apr 8;222:153436. doi: 10.1016/j.prp.2021.153436. Online ahead of print.

ABSTRACT

The diagnostic value of stromal changes in carcinomas, including prostate, is under debate; in terms of limited sample tissue of biopsy, in addition to glandular alterations, the stromal changes could have additional diagnostic value, but the results in clinical settings are controversial. The research aims to evaluate the potential of stromal changes as a supplementary tool to predict the presence of higher grade carcinomas in the prostate using Masson’s trichrome and Fanconi anemia complementation group M (FANCM) antibody stainings. 385 biopsies and corresponding radical prostatectomy specimens were analyzed to evaluate the rates of the diversity of ISUP grades. Of 128 upgraded prostatectomy cases, 82 were diagnosed with ISUP Gleason Grade 1 (GG1) in a biopsy. All 82 cancerous samples were stained with Masson’s trichrome and FACNM antibody and compared with 82 samples without cancer to see if there was a difference in stromal composition. Additionally, 50 GG1 samples without the upgrade were stained to demonstrate if stromal changes can predict less differentiated carcinomas in the prostate. In FANCM stained samples, the average percentage of positively staining stroma over the total in non-upgraded GG1 biopsies was 36 % (13-59 %, SD = 11); 34 % (9-58, SD = 13) in samples from the upgraded cancerous group, and 44 % (22-69, SD = 11) in samples without cancer. In Masson’s trichrome stained samples, with collagen quantified, the percentage in non-upgraded GG1 biopsies was 41 % (20-78 %, SD = 11); 44 % (23-89, SD = 15) in samples from upgraded cancerous group and 37 % (15-57, SD = 9) in samples without cancer. In both FANCM and Masson’s trichrome, no statistical significance was found between upgraded and non-upgraded groups (p = 0.84 and p = 0.5, respectively), although some upgrades from GG1 to GG4 showed extreme values. The statistical significance was found in cancerous vs. benign samples with both FANCM (p < 0.01) and Masson’s trichrome (p = 0.012). The main limiting factor is a significant overlap in staining intensity between cancerous and cancer-free groups.

PMID:33857855 | DOI:10.1016/j.prp.2021.153436

Phytomedicine. 2021 Mar 27;86:153559. doi: 10.1016/j.phymed.2021.153559. Online ahead of print.

ABSTRACT

BACKGROUND: Due to the diversity of the ingredients, the complexity of the mechanism of action, the uncertainty of the effective ingredients, coupled with the multiple species and multiple growing areas, the quality control (QC) of Traditional Chinese Medicines (TCMs) is challenging. Discovering and identifying effective compounds from the complex extracts of TCMs and then establishing a scientific QC method is the key to the holistic QC of TCMs.

PURPOSE: To develop an anti-lung-cancer-guided spectrum-effect relationship approach for the discovery of QC markers of the rhizome of Curcuma wenyujin (WEZ) and establish a bioactive compounds-based holistic QC method.

METHODS: The chemical profiling of the volatile oil (WVO) from 42 batches of WEZ collected from different growing areas was performed by GC-MS. The anti-lung cancer activity of different WVO samples was determined by CCK-8 assay against human lung cancer cells (A549). The apoptosis and cell cycle analysis under different concentrations of WVO were detected by flow cytometry. SIMCA-P software was used to perform multivariate statistical analysis on the chemical composition of different WVO samples and to find the different components. Active compounds were screened using a PLSR model of the spectrum-effect relationship. Bioactive compounds-based fingerprint and quantification of the leading bioactive compounds were developed by GC-MS and GC-FID, respectively.

RESULTS: Seventy-eight compounds were detected in WVO and 54 were successfully identified. The multivariate statistical analysis uncovered that WVO components and the anti-A549 activity of WVO at the concentration of 60 nl/ml differ greatly according to the origin of the plant. The WVO at the concentration of 60 nl/ml (IC₅₀) increased A549 cells apoptosis significantly with late and early apoptosis of 15.61% and 7.80%, and the number of cells in the G2/M phase were also increased significantly under this concentration. The spectrum-effect relationship analysis revealed that 44 compounds were positively correlated with their activities, and the result was verified by A549 cell viability assay. Sixteen positively correlated compounds were further selected as QC markers according to their relative amount > 0.5% and anticancer activity. Finally, the 16 QC markers-based GC-MS fingerprint was established to holistically control the quality of WEZ, and a GC-FID method was developed for the quantification of leading bioactive compounds, β-elemene and β-caryophyllene.

CONCLUSION: Based on an anti-lung-cancer-guided spectrum-effect relationship approach, the bioactive compounds-based holistic QC method was successfully developed for WEZ, which could provide a valuable reference for the QC of TCMs.

PMID:33857848 | DOI:10.1016/j.phymed.2021.153559

Psychiatry Res. 2021 Apr 6;300:113928. doi: 10.1016/j.psychres.2021.113928. Online ahead of print.

ABSTRACT

Cognitive impairment occurs across several neuropsychiatric diseases and impede everyday functioning and quality of life. Fully immersive Virtual Reality (VR) aid motivation and engagement and therefore has a potential to help overcome the obstacles in the field of cognitive rehabilitation. The aim of this systematic review is to investigate whether VR can be a useful intervention in cognitive rehabilitation transdiagnostically. We identified nine studies with randomized controlled trials following the PRISMA guidelines in databases Pubmed, Embase and PsychInfo. The trials were all evaluated through Cochrane Collaboration’s Risk of Bias. The studies were conducted in patients with mild cognitive impairment (k=4), schizophrenia (k=3), ADHD (k=1), or stroke (k=1) and involved 6-12 weeks of training. Overall, results showed improvement in some domains of cognition, primarily executive function and attention. The studies were pilot studies with 6-34 participants per treatment group. Risk of bias was either high (k=3) or moderate (some concerns) (k=6). Key reasons were suboptimal statistical analyses and lack of clarification on randomization and blinding of participants and assessors. In conclusion, this review found promising evidence for VR cognitive rehabilitation for neuropsychiatric illnesses. However, larger and methodologically stronger studies are warranted to establish the full potential of VR.

PMID:33857847 | DOI:10.1016/j.psychres.2021.113928

Comput Med Imaging Graph. 2021 Mar 14;90:101898. doi: 10.1016/j.compmedimag.2021.101898. Online ahead of print.

ABSTRACT

The hyperdense middle cerebral artery sign (HMCAS) representing a thromboembolus has been declared as a vital CT finding for intravascular thrombus in the diagnosis of acute ischemia stroke. Early recognition of HMCAS can assist in patient triage and subsequent thrombolysis or thrombectomy treatment. A total of 624 annotated head non-contrast-enhanced CT (NCCT) image scans were retrospectively collected from multiple public hospitals in Hong Kong. In this study, we present a deep Dissimilar-Siamese-U-Net (DSU-Net) that is able to precisely segment the lesions by integrating Siamese and U-Net architectures. The proposed framework consists of twin sub-networks that allow inputs of left and right hemispheres in head NCCT images separately. The proposed Dissimilar block fully explores the feature representation of the differences between the bilateral hemispheres. Ablation studies were carried out to validate the performance of various components of the proposed DSU-Net. Our findings reveal that the proposed DSU-Net provides a novel approach for HMCAS automatic segmentation and it outperforms the baseline U-Net and many state-of-the-art models for clinical practice.

PMID:33857830 | DOI:10.1016/j.compmedimag.2021.101898

Eur J Radiol. 2021 Apr 8;139:109697. doi: 10.1016/j.ejrad.2021.109697. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate intra-tumoral heterogeneity through a histogram analysis of quantitative parameters obtained from synthetic MRI (magnetic resonance imaging), and determine correlations of these histogram characteristics with prognostic factors and molecular subtypes of invasive ductal carcinoma (IDC).

METHODS: A total of 122 IDC from 122 women who underwent preoperative synthetic MRI and DCE (dynamic contrast enhancement)-MRI were investigated. The synthetic MRI parameters (T1, T2, and PD (proton density)) were obtained. For each parameter, the minimum, 10th percentile, mean, median, 90th percentile, maximum, skewness, and kurtosis values of tumor were calculated, and correlations with prognostic factors and subtypes were assessed. The Mann-Whitney U test or the Student^‘s t test were utilized to analyze the association between the histogram features of synthetic MRI parameters and prognostic factors. The Kruskal-Wallis test followed by the post-hoc test was used to analyze differences of synthetic MRI parameters among molecular subtypes.

RESULTS: IDC with high histopathologic grade showed statistically higher PD_maxium, T1_mean and T1_median values than those with low grade (p = 0.003, p = 0.007, p = 0.003). The T1_10th were significantly higher in cancers with PR (progesterone receptor) negativity than those with PR positivity (p = 0.005). ER-negative cancers had significant higher values of T2_10th, T2_mean, and T2_median than ER-positive cancers (p = 0.006, 0.002, and 0.006, respectively). The values of PD_median were significantly higher in IDC with HER2 (human epidermal growth factor receptor 2) positivity than those with HER2 negativity (p = 0.001). When discriminating molecular subtypes of IDC, the T2_mean achieved the highest performance. The T2_mean values of TN (triple-negative), luminal B and luminal A types are arranged in descending order (p < 0.0001).

CONCLUSIONS: Histogram features derived from synthetic MRI quantifies the distributions of tissue relaxation time and proton density, and may serve as a potential biomarker for discriminating histopathological grade, hormone receptor status, HER2 expression status and breast cancer subtypes.

PMID:33857828 | DOI:10.1016/j.ejrad.2021.109697

Ann Surg. 2021 Apr 7. doi: 10.1097/SLA.0000000000004902. Online ahead of print.

ABSTRACT

OBJECTIVE: This meta-analysis systematically reviewed published randomized control trials (RCTs) comparing sutured versus mesh-augmented hiatus hernia (HH) repair. Our primary endpoint was HH recurrence at short- and long-term follow-up. Secondary endpoints were: surgical complications, operative times, dysphagia and quality of life.

SUMMARY BACKGROUND DATA: Repair of large hiatus hernias is increasingly being performed. However, there is no consensus for the optimal technique for hiatal closure between sutured versus mesh-augmented (absorbable or non-absorbable) repair.

METHODS: A systematic review of Medline, Scopus (which encompassed Embase), Cochrane Central Register of Controlled Trials, Web of Science and PubMed was performed to identify relevant studies comparing mesh-augmented versus sutured HH repair. Data were extracted and compared by meta-analysis, using odds ratio and mean differences with 95% confidence intervals.

RESULTS: Seven RCTs were found which compared mesh-augmented (non-absorbable mesh: n = 296; absorbable mesh: n = 92) with sutured repair (n = 347). There were no significant differences for short-term hernia recurrence (defined as 6-12 months, 10.1% mesh versus 15.5% sutured, P = 0.22), long-term hernia recurrence (defined as 3-5 years, 30.7% mesh vs 31.3% sutured, P = 0.69), functional outcomes and patient satisfaction. The only statistically significant difference was that the mesh repair required a longer operation time (P = 0.05, OR 2.33, 95% CI 0.03-24.69).

CONCLUSIONS: Mesh repair for hiatus hernia does not offer any advantage over sutured hiatal closure. As both techniques deliver good and comparable clinical outcomes, a suture only technique is still an appropriate approach.

PMID:33856379 | DOI:10.1097/SLA.0000000000004902

J Med Internet Res. 2021 Apr 15;23(4):e23882. doi: 10.2196/23882.

ABSTRACT

BACKGROUND: Cardiac rehabilitation (CR) is clinically proven to reduce morbidity and mortality; however, many eligible patients do not enroll in treatment. Furthermore, many enrolled patients do not complete their full course of treatment. This is greatly influenced by socioeconomic factors but is also because of patients’ lack of understanding of the importance of their care and a lack of motivation to maintain attendance.

OBJECTIVE: This study aims to explore the potential benefits of virtual reality (VR) walking trails within CR treatment, specifically with regard to patient knowledge retention, satisfaction with treatment, and the overall attendance of treatment sessions.

METHODS: New CR patients were enrolled and randomized on a rolling basis to either the control group or intervention group. Intervention patients completed their time on the treadmill with VR walking trails, which included audio-recorded education, whereas control patients completed the standard of care therapy. Both groups were assisted by nursing staff for all treatment sessions. Primary outcomes were determined by assessing 6-minute walk test improvement. In addition, secondary outcomes of patients’ cardiac knowledge and satisfaction were assessed via a computer-based questionnaire; patient adherence to the recommended number of sessions was also monitored. Cardiac knowledge assessment included a prerehabilitation education quiz, and the same quiz was repeated at patients’ final visit and again at the 2-month follow-up. The satisfaction questionnaire was completed at the final visit.

RESULTS: Between January 2018 and May 2019, 72 patients were enrolled-41 in the intervention group and 31 in the control group. On the basis of the results of the prerehabilitation and postrehabilitation 6-minute walk test, no significant differences were observed between the intervention and control groups (P=.64). No statistical differences were observed between groups in terms of education (P=.86) or satisfaction (P=.32) at any time point. The control group had statistically more favorable rates of attendance, as determined by the risk group comparison (P=.02) and the comparison of the rates for completing the minimum number of sessions (P=.046), but no correlation was observed between the study group and reasons for ending treatment.

CONCLUSIONS: Although no improvements were seen in the VR intervention group over the control group, it is worth noting that limitations in the study design may have influenced these outcomes, not the medium itself. Furthermore, the qualitative information suggests that patients may have indeed enjoyed their experience with VR, even though quantitative satisfaction data did not capture this. Further considerations for how and when VR should be applied to CR are suggested in this paper.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03945201; https://clinicaltrials.gov/ct2/show/NCT03945201.

PMID:33856355 | DOI:10.2196/23882

JMIR Mhealth Uhealth. 2021 Apr 15;9(4):e25668. doi: 10.2196/25668.

ABSTRACT

BACKGROUND: Breastfeeding plays a major role in the health of mothers and babies and has the potential to positively shape an individual’s life both in the short and long term. In the United Kingdom (UK), although 81% of women initiate breastfeeding, only 1% of women breastfeed exclusively to 6 months as recommended by the World Health Organization. In the UK, women who are socially disadvantaged and younger are less likely to breastfeed at 6 to 8 weeks postpartum. One strategy that aims to improve these statistics is the Baby Buddy app, which has been designed and implemented by the UK charity Best Beginnings to be a universal intervention to help reduce health inequalities, including those in breastfeeding.

OBJECTIVE: This study aimed to retrospectively examine the development of Baby Buddy by applying the Behavior Change Wheel (BCW) framework to understand how it might increase breastfeeding self-efficacy, knowledge, and confidence.

METHODS: Retrospective application of the BCW was completed after the app was developed and embedded into maternity services. A three-stage process evaluation used triangulation methods and formalized tools to gain an understanding of the potential mechanisms and behaviors used in apps that are needed to improve breastfeeding rates in the UK. First, we generated a behavioral analysis by mapping breastfeeding barriers and enablers onto the Capability, Opportunity, and Motivation-Behavior (COM-B) system using documents provided by Best Beginnings. Second, we identified the intervention functions and policy categories used. Third, we linked these with the behavior change techniques identified in the app breastfeeding content using the Behavior Change Techniques Taxonomy (BCTTv1).

RESULTS: Baby Buddy is a well-designed platform that could be used to change breastfeeding behaviors. Findings from stage one showed that Best Beginnings had defined breastfeeding as a key behavior requiring support and demonstrated a thorough understanding of the context in which breastfeeding occurs, the barriers and enablers of breastfeeding, and the target actions needed to support breastfeeding. In stage two, Best Beginnings had used intervention and policy functions to address the barriers and enablers of breastfeeding. In stage three, Baby Buddy had been assessed for acceptability, practicability, effectiveness, affordability, safety, and equity. Several behavior change techniques that could assist women with decision making around breastfeeding (eg, information about health consequences and credible sources) and possibly affect attitudes and self-efficacy were identified. Of the 39 videos in the app, 19 (49%) addressed physical capabilities related to breastfeeding and demonstrated positive breastfeeding behaviors.

CONCLUSIONS: Applying a theoretical framework retrospectively to a mobile app is possible and results in useful information to understand potential health benefits and to inform future development. Future research should assess which components and behavioral techniques in the app are most effective in changing behavior and supporting breastfeeding.

PMID:33856351 | DOI:10.2196/25668

JMIR Med Inform. 2021 Apr 15;9(4):e18803. doi: 10.2196/18803.

ABSTRACT

BACKGROUND: Without timely diagnosis and treatment, tachycardia, also called tachyarrhythmia, can cause serious complications such as heart failure, cardiac arrest, and even death. The predictive performance of conventional clinical diagnostic procedures needs improvement in order to assist physicians in detecting risk early on.

OBJECTIVE: We aimed to develop a deep tachycardia onset prediction (TOP-Net) model based on deep learning (ie, bidirectional long short-term memory) for early tachycardia diagnosis with easily accessible data.

METHODS: TOP-Net leverages 2 easily accessible data sources: vital signs, including heart rate, respiratory rate, and blood oxygen saturation (SpO₂) acquired continuously by wearable embedded systems, and electronic health records, containing age, gender, admission type, first care unit, and cardiovascular disease history. The model was trained with a large data set from an intensive care unit and then transferred to a real-world scenario in the general ward. In this study, 3 experiments incorporated merging patients’ personal information, temporal memory, and different feature combinations. Six metrics (area under the receiver operating characteristic curve [AUROC], sensitivity, specificity, accuracy, F1 score, and precision) were used to evaluate predictive performance.

RESULTS: TOP-Net outperformed the baseline models on the large critical care data set (AUROC 0.796, 95% CI 0.768-0.824; sensitivity 0.753, 95% CI 0.663-0.793; specificity 0.720, 95% CI 0.645-0.758; accuracy 0.721; F1 score 0.718; precision 0.686) when predicting tachycardia onset 6 hours in advance. When predicting tachycardia onset 2 hours in advance with data acquired from our hospital using the transferred TOP-Net, the 6 metrics were 0.965, 0.955, 0.881, 0.937, 0.793, and 0.680, respectively. The best performance was achieved using comprehensive vital signs (heart rate, respiratory rate, and SpO₂) statistical information.

CONCLUSIONS: TOP-Net is an early tachycardia prediction model that uses 8 types of data from wearable sensors and electronic health records. When validated in clinical scenarios, the model achieved a prediction performance that outperformed baseline models 0 to 6 hours before tachycardia onset in the intensive care unit and 2 hours before tachycardia onset in the general ward. Because of the model’s implementation and use of easily accessible data from wearable sensors, the model can assist physicians with early discovery of patients at risk in general wards and houses.

PMID:33856350 | DOI:10.2196/18803

West J Emerg Med. 2021 Jan 22;22(2):435-444. doi: 10.5811/westjem.2020.10.48434.

ABSTRACT

INTRODUCTION: While trauma prognostication and triage scores have been designed for use in lower-resourced healthcare settings specifically, the comparative clinical performance between trauma-specific and general triage scores for risk-stratifying injured patients in such settings is not well understood. This study evaluated the Kampala Trauma Score (KTS), Revised Trauma Score (RTS), and Triage Early Warning Score (TEWS) for accuracy in predicting mortality among injured patients seeking emergency department (ED) care at the Centre Hospitalier Universitaire de Kigali (CHUK) in Rwanda.

METHODS: A retrospective, randomly sampled cohort of ED patients presenting with injury was accrued from August 2015-July 2016. Primary outcome was 14-day mortality and secondary outcome was overall facility-based mortality. We evaluated summary statistics of the cohort. Bootstrap regression models were used to compare areas under receiver operating curves (AUC) with associated 95% confidence intervals (CI).

RESULTS: Among 617 cases, the median age was 32 years and 73.5% were male. The most frequent mechanism of injury was road traffic incident (56.2%). Predominant anatomical regions of injury were craniofacial (39.3%) and lower extremities (38.7%), and the most common injury types were fracture (46.0%) and contusion (12.0%). Fourteen-day mortality was 2.6% and overall facility-based mortality was 3.4%. For 14-day mortality, TEWS had the highest accuracy (AUC = 0.88, 95% CI, 0.76-1.00), followed by RTS (AUC = 0.73, 95% CI, 0.55-0.92), and then KTS (AUC = 0.65, 95% CI, 0.47-0.84). Similarly, for facility-based mortality, TEWS (AUC = 0.89, 95% CI, 0.79-0.98) had greater accuracy than RTS (AUC = 0.76, 95% CI, 0.61-0.91) and KTS (AUC = 0.68, 95% CI, 0.53-0.83). On pairwise comparisons, RTS had greater prognostic accuracy than KTS for 14-day mortality (P = 0.011) and TEWS had greater accuracy than KTS for overall (P = 0.007) mortality. However, TEWS and RTS accuracy were not significantly different for 14-day mortality (P = 0.864) or facility-based mortality (P = 0.101).

CONCLUSION: In this cohort of emergently injured patients in Rwanda, the TEWS demonstrated the greatest accuracy for predicting mortality outcomes, with no significant discriminatory benefit found in the use of the trauma-specific RTS or KTS instruments, suggesting that the TEWS is the most clinically useful approach in the setting studied and likely in other similar ED environments.

PMID:33856336 | DOI:10.5811/westjem.2020.10.48434