Stimulated Raman Histology Interpretation by Artificial Intelligence Provides Near-Real-Time Pathologic Feedback for Unprocessed Prostate Biopsies.

PURPOSE: Stimulated Raman histology is an innovative technology that generates real-time, high-resolution microscopic images of unprocessed tissue, significantly reducing prostate biopsy interpretation time. This study aims to evaluate the ability for an artificial intelligence convolutional neural network to interpretate prostate biopsy histologic images created with stimulated Raman histology. MATERIALS AND METHODS: Unprocessed, unlabeled prostate biopsies were prospectively imaged using a stimulated Raman histology microscope. Following stimulated Raman histology creation, the cores underwent standard pathological processing and interpretation by at least 2 genitourinary pathologists to establish a ground truth assessment. A network, trained on 303 prostate biopsies from 100 participants, was used to measure the accuracy, sensitivity, and specificity of detecting prostate cancer on stimulated Raman histology relative to conventional pathology. The performance of the artificial intelligence was evaluated on an independent 113-biopsy test set. RESULTS: Prostate biopsy images obtained through stimulated Raman histology can be generated within a time frame of 2 to 2.75 minutes. The artificial intelligence system achieved a rapid classification of prostate biopsies with cancer, with a potential identification time of approximately 1 minute. The artificial intelligence demonstrated an impressive accuracy of 96.5% in detecting prostate cancer. Moreover, the artificial intelligence exhibited a sensitivity of 96.3% and a specificity of 96.6%. CONCLUSIONS: Stimulated Raman histology generates microscopic images capable of accurately identifying prostate cancer in real time, without the need for sectioning or tissue processing. These images can be interpreted by artificial intelligence, providing physicians with near-real-time pathological feedback during the diagnosis or treatment of prostate cancer.

Effect of laser bleaching, ultrasonic scaling and powered tooth brushing on surface roughness and bacterial adherence of class V composite restorations.

Objective: To evaluate and compare the effect of diode laser assisted bleaching, ultrasonic scaling and powered tooth brushing on surface roughness and bacterial adherence on class V cavities restored with composites. Materials and methods: A total of one hundred and twenty samples (40 samples each of Brilliant Everglow, Beautifil II and Heytec-N) were prepared in standardized stainless steel molds. The samples were further subdivided into four subgroups i.e. one control group (without any intervention) and three experimental groups - diode laser assisted bleaching, ultrasonic scaling and powered tooth brushing consisting of 10 sample each. Surface roughness was measured quantitatively with the help of 3D Optical Profilometer. For bacterial adherence analysis S. mutans strain (ATCC 25175) was cultured in BHI medium and samples were evaluated for the presence of viable bacteria using the Colony Forming Unit (CFU) count. Results obtained were then tabulated and subjected to statistical analysis. Results: Diode laser bleaching caused a significant increase in surface roughness and bacterial adherence with lowest mean change exhibited by Heytec-N followed by Beautifil II and highest by Brilliant Everglow group. Similarly, Ultrasonic scaling increased the surface roughness of all the three tested samples with significant difference between the groups. Powered tooth brushing had no effect on the surface roughness and bacterial adherence of the tested composites. Conclusion: Diode assisted laser bleaching and ultrasonic caused significantly higher surface roughness and bacterial adherence values for all the tested composites. It may therefore be recommended to do finishing and polishing of restorations after such procedures.

Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Oral health status and absence from school among 12 year olds.

OBJECTIVE: To assess dental caries, periodontal status, malocclusion and absenteeism from school among 12-year-olds in Bhopal district, Central India. MATERIALS AND METHODS: Two-stage random sample of 1238 school children. Decayed missing filled teeth (DMFT), Significant caries index (SiC), community periodontal index (CPI) and dental aesthetic index (DAI) were used to record dental caries, periodontal status and malocclusion. Information on absence from school in the previous year due to pain/discomfort in the teeth or mouth was collected via interviews. Generalized structural equation modelling (GSEM) examined the direct and indirect predictors of absence from school. RESULTS: A total of 39.1%, 17.3% and 23.9% of children had dental caries, calculus and gingival bleeding respectively. Mean DMFT and SiC scores were 1.82± 1.36 and 3.15 ± 1.47. 5,127 school hours were missed due to oral health problems per 1,000 children. None of the studied variables predicted absence from school. Utilization of dental care was associated directly with gender and malocclusion (p⟨ 0.001). Periodontal status was associated with male gender, nuclear families, tobacco consumption, and malocclusion (p⟨ 0.001). Higher DMFT was associated with male gender, malocclusion and experience of pain/discomfort (p⟨ 0.001). CONCLUSIONS: Poor oral health and a high prevalence of untreated dental caries were noted. Despite a considerable number of missed school hours reported due to dental conditions, none of the studied variables predicted absence from school.

Differential 18F-NaF uptake in various compartments in knee osteoarthritis: an observational study using PET/MRI.

AIM: To investigate if the pattern of fluorine-18-labelled sodium fluoride (18F-NaF) uptake on integrated positron-emission tomography (PET)/magnetic resonance imaging (MRI) of bone marrow lesions (BML) and osteophytes differs between different knee compartments. MATERIALS AND METHODS: Sixteen patients with no prior history of knee injury with or without pain were recruited for the study. The images of both knees were acquired on simultaneous PET/MRI. The acquisition was done after 45 minutes of intravenous injection of 18F-NaF 185-370 MBq (5-10 mCi) for 40 minutes. Each knee was divided into eight compartments patella, trochlea, medial central femur, lateral central femur, medial posterior femur, lateral posterior femur, medial tibia, lateral tibia, and cruciate ligament insertion specifically for BML. BML and osteophytes were scored using MRI Osteoarthritis Knee Score (MOAKS) criteria and their corresponding maximum standardised uptake values (SUVmax) recorded. RESULTS: BML and osteophytes both showed statistically significant differences among knee compartments, i.e., p-value <0.000 and < 0.043 respectively. SUVmax for BML and osteophytes was greatest in the medial tibia. CONCLUSION: 18F-NaF PET/MRI showed that BML and osteophytes had differential uptake values due to bone remodelling amongst the various knee compartments and this may help to design disease-modifying osteoarthritis drugs in the future.

What is a better modality of maxillomandibular fixation: bone-supported arch bars or Erich arch bars? A systematic review and meta-analysis.

Any procedure that aims to manage maxillofacial fracture is incomplete without meticulous maxillomandibular fixation (MMF). For decades, Erich arch bars (EABs) have been used for this purpose, but with the advent of bone-supported arch bars (BSABs), more surgeons now prefer them to conventional EABs. The present study was designed to identify which of the two methods is best. An exhaustive literature search was conducted in June 2020 on various electronic databases to select studies that compared EABs and BSABs. Outcomes such as duration of placement, stability, oral hygiene, and complications such as damage to the roots of teeth and needle-stick injury, were analysed. A total of 716 studies were identified, of which seven were eligible for inclusion. The meta-analysis showed that the use of BSABs is significantly faster with no needle penetration and better oral hygiene. Both arch bars are equally stable, but root damage is an associated complication. The available literature to date shows that BSABs are a better option than EABs. However, further research is recommended, as these studies are associated with various confounding factors.

Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922). RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001). CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

Multiparametric Evaluation in Differentiating Glioma Recurrence from Treatment-Induced Necrosis Using Simultaneous 18F-FDG-PET/MRI: A Single-Institution Retrospective Study.

BACKGROUND AND PURPOSE: Differentiating glioma recurrence from treatment-induced necrosis can be a challenge on conventional imaging. This study aimed to assess the diagnostic performance of each functional MR imaging and PET parameter derived by using simultaneous FDG-PET/MR imaging individually and in combination in the evaluation of suspected glioma recurrence. MATERIALS AND METHODS: Thirty-five treated glioma patients with 41 enhancing lesions (World Health Organization grade II = 9, III = 13, IV = 19) on MR imaging after an operation followed by radiation therapy and/or chemotherapy formed part of this study. Using PET/MR imaging, we calculated the normalized mean relative CBV, mean ADC, Cho/Cr, and maximum and mean target-to-background ratios. Statistical analysis was performed to determine the diagnostic performance of each parameter by receiver operating characteristic analysis individually and in combination with multivariate receiver operating characteristic analysis for the detection of glioma recurrence. Histopathology or clinicoradiologic follow-up was considered the criterion standard. RESULTS: Of 35 patients, 25 (30 lesions) were classified as having a recurrence and 10 (11 lesions) patients as having treatment-induced necrosis. Parameters like rCBVmean (mean relative CBV), ADCmean, Cho/Cr, and maximum and mean target-to-background ratios were statistically significant in the detection of recurrent lesions with an accuracy of 77.5%, 78.0%, 90.9%, 87.8%, and 87.8%, respectively. On multivariate receiver operating characteristic analysis, the combination of all 3 MR imaging parameters resulted in an area under the curve of 0.913 ± 0.053. Furthermore, an area under the curve of 0.935 ± 0.046 was obtained when MR imaging parameters (ADCmean and Cho/Cr) were combined with the PET parameter (mean target-to-background ratio), demonstrating an increase in diagnostic accuracy. CONCLUSIONS: Simultaneous PET/MR imaging with FDG offers correlative and synergistic multiparametric assessment of glioma recurrence with increased accuracy and clinical utility.

Iatrogenic Menopause After Treatment for Cervical Cancer.

The ever-improving prognosis of women diagnosed with cervical cancer has meant that survivorship and treatment-related sequelae are being brought more into the spotlight in an attempt to try to reduce morbidity and improve women's long-term health. However, there are many issues surrounding an iatrogenic menopause in cervical cancer, a variety of potential management options and barriers to treatment. Women who have become menopausal under the age of 45 years as a result of cervical cancer are significantly less likely to start hormone replacement therapy (HRT) or continue it long term as compared with those who have undergone a surgical menopause for a benign reason. High profile media reports raising concerns about the safety of HRT use have left many women reluctant to consider HRT as a therapeutic option for menopausal symptoms and many are seeking to use complementary/alternative medicine, including non-pharmacological interventions, to alleviate symptoms. The benefits of HRT in this population have been shown to reduce these effects, although adherence to treatment regimens is a challenge due to poor compliance, which is in part due to the fear of a second malignancy. The development of non-HRT-based interventions to ameliorate menopausal symptoms and reduce the long-term health consequences are needed for women who choose not to take HRT.

Does normalisation improve the diagnostic performance of apparent diffusion coefficient values for prostate cancer assessment? A blinded independent-observer evaluation.

AIM: To evaluate the performance of normalised apparent diffusion coefficient (ADC) values for prostate cancer assessment when performed by independent observers blinded to histopathology findings. MATERIALS AND METHODS: Fifty-eight patients undergoing 3 T phased-array coil magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI; maximal b-value 1000 s/mm(2)) before prostatectomy were included. Two radiologists independently evaluated the images, unaware of the histopathology findings. Regions of interest (ROIs) were drawn within areas showing visually low ADC within the peripheral zone (PZ) and transition zone (TZ) bilaterally. ROIs were also placed within regions in both lobes not suspicious for tumour, allowing computation of normalised ADC (nADC) ratios between suspicious and non-suspicious regions. The diagnostic performance of ADC and nADC were compared. RESULTS: For PZ tumour detection, ADC achieved significantly higher area under the receiver operating characteristic curve (AUC; p=0.026) and specificity (p=0.021) than nADC for reader 1, and significantly higher AUC (p=0.025) than nADC for reader 2. For TZ tumour detection, nADC achieved significantly higher specificity (p=0.003) and accuracy (p=0.004) than ADC for reader 2. For PZ Gleason score >3+3 tumour detection, ADC achieved significantly higher AUC (p=0.003) and specificity (p=0.005) than nADC for reader 1, and significantly higher AUC (p=0.023) than nADC for reader 2. For TZ Gleason score >3+3 tumour detection, ADC achieved significantly higher specificity (p=0.019) than nADC for reader 1. CONCLUSION: In contrast to prior studies performing unblinded evaluations, ADC was observed to outperform nADC overall for two independent observers blinded to the histopathology findings. Therefore, although strategies to improve the utility of ADC measurements in prostate cancer assessment merit continued investigation, caution is warranted when applying normalisation to improve diagnostic performance in clinical practice.

TOOKAD® Soluble focal therapy: pooled analysis of three phase II studies assessing the minimally invasive ablation of localized prostate cancer.

PURPOSE: To evaluate the 6-month effects of the recommended drug and light dosage in focal vascular-targeted photodynamic therapy (VTP) using TOOKAD(®) Soluble in patients with localized prostate cancer (LPCa). METHODS: We performed a pooled analysis of 117 men with LPCa, PSA <10 ng/mL, and Gleason score ≤ 7 (3 + 4), from 3 studies who received a 10-min intravenous infusion of a single dose of 4 mg/kg TOOKAD(®) Soluble, activated by a 753-nm light at 200 J/cm delivered in the prostate by transperineal fibres under transrectal ultrasound guidance. Primary endpoint was 6-month negative biopsies in the treated lobe(s). PSA was measured at month 1, 3, and 6. Magnetic resonance imaging was performed at day 7, month 3, and 6. International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and adverse events were reported at day 7, month 1, 3, and 6. RESULTS: Month 6 negative biopsy rate was 68.4 % in the overall evaluable population (N = 114) and 80.6 % for patients treated by hemiablation with light density index (LDI) ≥ 1 (N = 67). Mean prostate necroses at week-1 were 76.5 and 86.3 %, respectively. In both groups, PSA levels at month 6 decreased by 2.0 ng/mL. Small changes from baseline for IPSS and IIEF-5 indicated a slight improvement in urinary function and a slight deterioration in sexual function. CONCLUSIONS: Focal VTP treatment with TOOKAD(®) Soluble at 4 mg/kg and 200 J/cm resulted in a negative 6-month biopsy rate of 68.4 % for the whole population and 80.6 % for patients treated by hemiablation with LDI ≥ 1. The treatment was well tolerated. Two phase III studies will reach completion in early 2015.

Assessment of change in prostate volume and shape following surgical resection through co-registration of in-vivo MRI and fresh specimen ex-vivo MRI.

AIM: To compare the size and shape of the prostate between in-vivo and fresh ex-vivo magnetic resonance imaging (MRI), in order to quantify alterations in the prostate resulting from surgical resection. MATERIAL AND METHOD: Ten patients who had undergone 3 T prostate MRI using a phased-array coil and who were scheduled for prostatectomy were included in this prospective study. The ex-vivo specimen underwent MRI prior to formalin fixation or any other histopathological processing. Prostate volume in vivo and ex vivo was assessed using planimetry. Prostate shape was assessed by calculating ratios between the diameters of the prostate in all three dimensions. RESULTS: Mean prostate volume was significantly smaller ex vivo than in vivo (39.7 ± 18.6 versus 50.8 ± 26.8 cm(3); p = 0.008), with an average change in volume of -19.5%. The right-to-left (RL)/anteroposterior (AP) ratio of the prostate, representing the shape of the prostate within its axial plane, was significantly larger ex vivo than in vivo (1.33 ± 0.14 versus 1.21 ± 0.12; p = 0.015), with an average percent change in RL/AP ratio of the prostate of +12.2%. There was no significant difference between in-vivo and ex-vivo acquisitions in terms of craniocaudal (CC)/AP (p = 0.963, median change = -2.1%) or RL/CC (p = 0.265, median change = +1.3%) ratios. CONCLUSION: The observed volume and shape change following resection has not previously been assessed by comparison of in-vivo and fresh ex-vivo MRI and likely represents loss of vascularity and of connective tissue attachments in the ex-vivo state. These findings have implications for co-registration platforms under development to facilitate improved understanding of the accuracy of MRI in spatial localization of prostate tumours.

Synthesis of single-enantiomer bioactive molecules: a brief overview.

Chiral-center enantiomers have been shown to differ significantly in biological activity, pharmacodynamics, pharmacokinetics and toxicity. New developments in the stereoselective organic synthesis have enriched the vast literature of synthetic methodologies applicable to access natural products as well as bioactive molecules. These compounds also include new drugs, drug candidates and reagents used to explore biological processes. The article reviews the synthesis of optically pure drugs, biologically active intermediates and amino alcohols by using different methods.

Influence of fiber inserts, type of composite, and gingival margin location on the microleakage in Class II resin composite restorations.

This study evaluated the influence of fiber inserts, type of composites, and location of the gingival seat on microleakage in Class II resin composite restorations. Fifty noncarious human third molars were selected for the study. Standardized Class II box type cavities were prepared on the mesial and distal side of 45 teeth. The gingival margin was placed above the cementoenamel junction (CEJ) on the mesial side and below the CEJ on the distal side. The remaining five teeth received no cavity preparations. The prepared samples were divided randomly on the basis of type of composite and presence or absence of fiber inserts, into four experimental groups of 10 teeth each and two control groups of five teeth each. The groups were defined as follows: group I (n=10) - Z350 XT; group II (n=10) - Z350 XT with fibers; group III (n=10) - P90; group IV (n=10) - P90 with fibers; and group V (n=5) - positive controls, cavities were not restored; group VI (n=5) - negative controls, no cavities were prepared. The samples were stored in distilled water in incubator at 37°C for 24 hours and then subjected to 500 cycles of thermocycling (5°C and 55°C) with a dwell time of 15 seconds. They were then placed in a 2% methylene blue dye solution for 24 hours at 37°C. Samples were sectioned longitudinally and evaluated for microleakage at the occlusal and gingival margin under a stereomicroscope at 20× magnification. Kruskal-Wallis and Mann-Whitney U-tests were used to compare the mean leakage scores. Restorations with gingival margins in enamel showed significantly less microleakage. Significant reduction in microleakage was observed in groups restored with P90 composite than those restored with Z350 XT. No improvement in microleakage was observed with the use of fiber inserts (p>0.05).

Preliminary experience with a novel method of three-dimensional co-registration of prostate cancer digital histology and in vivo multiparametric MRI.

AIM: To assess a novel method of three-dimensional (3D) co-registration of prostate cancer digital histology and in-vivo multiparametric magnetic resonance imaging (mpMRI) image sets for clinical usefulness. MATERIAL AND METHODS: A software platform was developed to achieve 3D co-registration. This software was prospectively applied to three patients who underwent radical prostatectomy. Data comprised in-vivo mpMRI [T2-weighted, dynamic contrast-enhanced weighted images (DCE); apparent diffusion coefficient (ADC)], ex-vivo T2-weighted imaging, 3D-rebuilt pathological specimen, and digital histology. Internal landmarks from zonal anatomy served as reference points for assessing co-registration accuracy and precision. RESULTS: Applying a method of deformable transformation based on 22 internal landmarks, a 1.6 mm accuracy was reached to align T2-weighted images and the 3D-rebuilt pathological specimen, an improvement over rigid transformation of 32% (p = 0.003). The 22 zonal anatomy landmarks were more accurately mapped using deformable transformation than rigid transformation (p = 0.0008). An automatic method based on mutual information, enabled automation of the process and to include perfusion and diffusion MRI images. Evaluation of co-registration accuracy using the volume overlap index (Dice index) met clinically relevant requirements, ranging from 0.81-0.96 for sequences tested. Ex-vivo images of the specimen did not significantly improve co-registration accuracy. CONCLUSION: This preliminary analysis suggests that deformable transformation based on zonal anatomy landmarks is accurate in the co-registration of mpMRI and histology. Including diffusion and perfusion sequences in the same 3D space as histology is essential further clinical information. The ability to localize cancer in 3D space may improve targeting for image-guided biopsy, focal therapy, and disease quantification in surveillance protocols.