Automated reporting of cervical biopsies using artificial intelligence.

When detected at an early stage, the 5-year survival rate for people with invasive cervical cancer is 92%. Being aware of signs and symptoms of cervical cancer and early detection greatly improve the chances of successful treatment. We have developed an Artificial Intelligence (AI) algorithm, trained and evaluated on cervical biopsies for automated reporting of digital diagnostics. The aim is to increase overall efficiency of pathological diagnosis and to have the performance tuned to high sensitivity for malignant cases. Having a tool for triage/identifying cancer and high grade lesions may potentially reduce reporting time by identifying areas of interest in a slide for the pathologist and therefore improving efficiency. We trained and validated our algorithm on 1738 cervical WSIs with one WSI per patient. On the independent test set of 811 WSIs, we achieved 93.4% malignant sensitivity for classifying slides. Recognising a WSI, with our algorithm, takes approximately 1.5 minutes on the NVIDIA Tesla V100 GPU. Whole slide images of different formats (TIFF, iSyntax, and CZI) can be processed using this code, and it is easily extendable to other formats.

Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Lensectomy as treatment for refractory or progressive retinopathy of prematurity narrow-angle glaucoma.

We present the case of a patient with a history of laser-treated retinopathy of prematurity (ROP) who developed narrow angles and intermittent angle closure. Despite laser peripheral iridotomy/iridoplasty, 1 year later, the patient had recurrent narrowing that resolved following clear lens extraction with intraocular lens placement. This case highlights the importance of continued monitoring for narrow angles in patients with ROP history.

Genetic testing for infantile nystagmus syndrome with or without associated findings.

PURPOSE: To review the published literature assessing the clinical utility of genetic testing in individuals with infantile nystagmus syndrome (INS), defined as binocular conjugate nystagmus and onset prior to 6 months of age, with or without associated findings. METHODS: A literature search was last conducted in October 2022. The results were limited to articles published in English. The search yielded 517 abstracts, of which 72 papers were reviewed in full text. Of these papers, 4 met the criteria for inclusion and were graded by a study methodologist. RESULTS: The 4 studies that met inclusion criteria used next-generation sequencing with gene panels ranging from 31 to 336 genes. The overall molecular diagnostic rate ranged from 35% to 60% in the included studies, although the yield was higher when genetic testing was guided by clinical phenotyping (approximately 80%) and in the subsets of patients with a family history (up to 88%). As many as 30% of patients tested had a reclassification of the diagnosis based on the genetic testing results. CONCLUSIONS: Genetic testing has the potential to provide a definitive diagnosis and identify treatable conditions in patients presenting with INS, especially when considered in conjunction with clinical phenotyping and family history.

Levodopa/Carbidopa to Augment the Treatment of Amblyopia: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the use of levodopa/carbidopa to augment the treatment of amblyopia. METHODS: Literature searches for English language studies were last conducted in October 2022 in the PubMed database with no date restrictions. The combined searches yielded 55 articles, of which 23 were reviewed in full text. Twelve of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. Nine studies were rated level I, and 3 studies were rated level II; there were no level III studies. RESULTS: The duration of treatment was limited to 3 to 16 weeks because of concern about long-term adverse effects such as tardive dyskinesia. This complication was not reported in any of the study participants. The dose of levodopa ranged from 1.5 to 8.3 mg/kg/day, generally divided into 3 daily doses. The carbidopa dose was approximately 25% of the levodopa dose in all treatments. Evidence from these studies indicates that augmenting traditional patch occlusion therapy with the oral administration of levodopa/carbidopa can improve the vision of amblyopic children, but the effect was small (0.17-0.3 logarithm of the minimum angle of resolution [logMAR] units) and only statistically significant when compared with patching alone in 2 of the 12 studies cited. Regression of vision was reported in the majority of studies (9 of 12 reported; range, 0-0.17 logMAR unit regression) after discontinuation of therapy. Short-term side effects of the medications were not consistently reported but were most frequently mild and included headache and nausea. CONCLUSIONS: The best available evidence is currently insufficient to show that augmenting amblyopia therapy using up to 16 weeks of levodopa/carbidopa will result in meaningful improvement in visual acuity. Given the potential for significant side effects such as tardive dyskinesia with long-term therapy, levodopa/carbidopa does not appear to be a viable option for amblyopia therapy FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A Pilot Randomized Clinical Trial of Base-in Relieving Prism Spectacle Treatment of Intermittent Exotropia.

SIGNIFICANCE: This pilot randomized trial, the first to evaluate a specific base-in relieving prism treatment strategy for childhood intermittent exotropia, did not support proceeding to a full-scale clinical trial. Defining and measuring prism adaptation in children with intermittent exotropia are challenging and need further study. PURPOSE: This study aimed to determine whether to proceed to a full-scale trial of relieving base-in prism spectacles versus refractive correction alone for children with intermittent exotropia. METHODS: Children 3 years old to those younger than 13 years with distance intermittent exotropia control score of ≥2 points on the Intermittent Exotropia Office Control Scale (Strabismus 2006;14:147-150; 0 [phoria] to 5 [constant]), ≥1 episode of spontaneous exotropia, and 16 to 35∆ by prism-and-alternate-cover test, who did not fully prism adapt on a 30-minute in-office prism-adaptation test were randomized to base-in relieving prism (40% of the larger of distance and near exodeviations) or nonprism spectacles for 8 weeks. A priori criteria to conduct a full-scale trial were defined for the adjusted treatment group difference in mean distance control: "proceed" (≥0.75 points favoring prism), "uncertain" (>0 to <0.75 points favoring prism), or "do not proceed" (≥0 points favoring nonprism). RESULTS: Fifty-seven children (mean age, 6.6 ± 2.2 years; mean baseline distance control, 3.5 points) received prism (n = 28) or nonprism (n = 29) spectacles. At 8 weeks, mean control values were 3.6 and 3.3 points in prism (n = 25) and nonprism (n = 25) groups, respectively, with an adjusted difference of 0.3 points (95% confidence interval, -0.5 to 1.1 points) favoring nonprism (meeting our a priori "do not proceed" criterion). CONCLUSIONS: Base-in prism spectacles, equal to 40% of the larger of the exodeviations at distance or near, worn for 8 weeks by 3- to 12-year-old children with intermittent exotropia did not yield better distance control than refractive correction alone, with the confidence interval indicating that a favorable effect of 0.75 points or larger is unlikely. There was insufficient evidence to warrant a full-scale randomized trial.

Risk of stroke-specific mortality after radiotherapy in patients with primary brain tumours.

Introduction: Stroke is an established complication in cancer patients, amongst whom brain tumour patients have the highest risk of fatal stroke. Radiotherapy is an important treatment for brain tumours and is associated with increased risk of cerebrovascular disease. However, the impact of brain irradiation on stroke-related deaths in brain tumour patients is unknown, and the timing of any effect uncertain. This study investigates the relationship between radiotherapy and stroke-specific mortality (SSM) in patients with primary brain tumours. Methods: Patients of any age diagnosed with histologically confirmed primary brain tumours between 1992 and 2015 were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database. Primary outcome was impact of radiotherapy on 5-year SSM. Cumulative SSM rates under competing risk assumptions were estimated and stratified by intervention type. Time-dependent hazard ratios were estimated to identify when the radiotherapy impact was greatest. Results: 85,284 patients with primary brain tumour diagnoses were analysed. Overall, the 5-year cumulative SSM rate was low (0.6%) with the highest rate (0.76%) in patients receiving no treatment, in whom it mainly occurred < 1 month after diagnosis. SSM rates were lower in patients treated with radiotherapy alone (0.27%) or radiotherapy plus surgery (0.24%); stroke-related deaths also occurred later in these groups. While these patterns were observed in both glioblastoma and non-glioblastoma patients, stroke deaths tended to occur later in non-glioblastoma patients receiving radiotherapy. Relative to the 'no treatment' group, the highest risk of stroke mortality in radiotherapy treated patients occurred 3.5-4 years after diagnosis. Conclusion: The risk of SSM is low in patients with primary brain tumours and is not increased by radiotherapy. Two different patterns were observed: acute stroke mortality in patients receiving no treatment, and delayed stroke mortality in patients receiving radiotherapy (+/- surgery) with the latter peaking 3.5-4 years after diagnosis.

Circulating proteins to predict COVID-19 severity.

Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.

Whole-population trends in pathology-confirmed cancer incidence in Northern Ireland, Scotland and Wales during the SARS-CoV-2 pandemic: A retrospective observational study.

INTRODUCTION: The COVID-19 epidemic interrupted normal cancer diagnosis procedures. Population-based cancer registries report incidence at least 18 months after it happens. Our goal was to make more timely estimates by using pathologically confirmed cancers (PDC) as a proxy for incidence. We compared the 2020 and 2021 PDC with the 2019 pre-pandemic baseline in Scotland, Wales, and Northern Ireland (NI). METHODS: Numbers of female breast (ICD-10 C50), lung (C33-34), colorectal (C18-20), gynaecological (C51-58), prostate (C61), head and neck (C00-C14, C30-32), upper gastro-intestinal (C15-16), urological (C64-68), malignant melanoma (C43), and non-melanoma skin (NMSC) (C44) cancers were counted. Multiple pairwise comparisons generated incidence rate ratios (IRR). RESULTS: Data were accessible within 5 months of the pathological diagnosis date. Between 2019 and 2020, the number of pathologically confirmed malignancies (excluding NMSC) decreased by 7315 (14.1 %). Scotland experienced early monthly declines of up to 64 % (colorectal cancers, April 2020 versus April 2019). Wales experienced the greatest overall change in 2020, but Northern Ireland experienced the quickest recovery. The pandemic's effects varied by cancer type, with no significant change in lung cancer diagnoses in Wales in 2020 (IRR 0.97 (95 % CI 0.90-1.05)), followed by an increase in 2021 (IRR 1.11 (1.03-1.20). CONCLUSION: PDC are useful in reporting cancer incidence quicker than cancer registrations. Temporal and geographical differences between participating countries mirrored differences in responses to the COVID-19 pandemic, indicating face validity and the potential for quick cancer diagnosis assessment. To verify their sensitivity and specificity against the gold standard of cancer registrations, however, additional research is required.

Co-occurring homelessness, justice involvement, opioid dependence and psychosis: a cross-sectoral data linkage study.

BACKGROUND: Administrative data offer unique opportunities for researching experiences which pose barriers to participation in primary research and household surveys. Experiencing multiple social disadvantages is associated with very poor health outcomes, but little is known about how often this occurs and what combinations are most common. We linked administrative data across public services to create a novel population cohort containing information on experiences of homelessness, justice involvement, opioid dependence and psychosis. METHODS: We securely linked administrative data from (i) a population register derived from general practitioner registrations; (ii) local authority homelessness applications; (iii) prison records; (iv) criminal justice social work reports; (v) community dispensing for opioid substitution therapy; and (vi) a psychosis clinical register, for people aged ≥18 years resident in Glasgow, Scotland between 01 April 2010 and 31 March 2014. We estimated period prevalence and compared demographic characteristics for different combinations. RESULTS: Of 536 653 individuals in the cohort, 28 112 (5.2%) had at least one of the experiences of interest during the study period and 5178 (1.0%) had more than one. Prevalence of individual experiences varied from 2.4% (homelessness) to 0.7% (psychosis). The proportion of people with multiple co-occurring experiences was highest for imprisonment (50%) and lowest for psychosis (14%). Most combinations showed a predominance of men living in the most deprived areas of Scotland. CONCLUSIONS: Cross-sectoral record linkage to study multiple forms of social disadvantage showed that co-occurrence of these experiences was relatively common. Following this demonstration of feasibility, these methods offer opportunities for evaluating the health impacts of policy and service change.

Detection of malignancy in whole slide images of endometrial cancer biopsies using artificial intelligence.

In this study we use artificial intelligence (AI) to categorise endometrial biopsy whole slide images (WSI) from digital pathology as either "malignant", "other or benign" or "insufficient". An endometrial biopsy is a key step in diagnosis of endometrial cancer, biopsies are viewed and diagnosed by pathologists. Pathology is increasingly digitised, with slides viewed as images on screens rather than through the lens of a microscope. The availability of these images is driving automation via the application of AI. A model that classifies slides in the manner proposed would allow prioritisation of these slides for pathologist review and hence reduce time to diagnosis for patients with cancer. Previous studies using AI on endometrial biopsies have examined slightly different tasks, for example using images alongside genomic data to differentiate between cancer subtypes. We took 2909 slides with "malignant" and "other or benign" areas annotated by pathologists. A fully supervised convolutional neural network (CNN) model was trained to calculate the probability of a patch from the slide being "malignant" or "other or benign". Heatmaps of all the patches on each slide were then produced to show malignant areas. These heatmaps were used to train a slide classification model to give the final slide categorisation as either "malignant", "other or benign" or "insufficient". The final model was able to accurately classify 90% of all slides correctly and 97% of slides in the malignant class; this accuracy is good enough to allow prioritisation of pathologists' workload.

Dysregulation of Gene Expression of Key Signaling Mediators in PBMCs from People with Type 2 Diabetes Mellitus.

Diabetes is currently the fifth leading cause of death by disease in the USA. The underlying mechanisms for type 2 Diabetes Mellitus (DM2) and the enhanced susceptibility of such patients to inflammatory disorders and infections remain to be fully defined. We have recently shown that peripheral blood mononuclear cells (PBMCs) from non-diabetic people upregulate expression of inflammatory genes in response to proteasome modulators, such as bacterial lipopolysaccharide (LPS) and soybean lectin (LEC); in contrast, resveratrol (RES) downregulates this response. We hypothesized that LPS and LEC will also elicit a similar upregulation of gene expression of key signaling mediators in (PBMCs) from people with type 2 diabetes (PwD2, with chronic inflammation) ex vivo. Unexpectedly, using next generation sequencing (NGS), we show for the first time, that PBMCs from PwD2 failed to elicit a robust LPS- and LEC-induced gene expression of proteasome subunit LMP7 (PSMB8) and mediators of T cell signaling that were observed in non-diabetic controls. These repressed genes included: PSMB8, PSMB9, interferon-γ, interferon-λ, signal-transducer-and-activator-of-transcription-1 (STAT1), human leukocyte antigen (HLA DQB1, HLA DQA1) molecules, interleukin 12A, tumor necrosis factor-α, transporter associated with antigen processing 1 (TAP1), and several others, which showed a markedly weak upregulation with toxins in PBMCs from PwD2, as compared to those from non-diabetics. Resveratrol (proteasome inhibitor) further downregulated the gene expression of these inflammatory mediators in PBMCs from PwD2. These results might explain why PwD2 may be susceptible to infectious disease. LPS and toxins may be leading to inflammation, insulin resistance, and thus, metabolic changes in the host cells.

Establishing local manufacture of PPE for healthcare workers in the time of a global pandemic.

A face shield is a secondary personal protective equipment (PPE) for healthcare workers (HCW). Worn with the appropriate face masks/respirators, it provides short term barrier protection against potentially infectious droplet particles. Coronavirus disease 2019 (COVID-19) caused a spike in demand for PPE, leading to a shortage and risking the safety of HCW. Transport restrictions further challenged the existing PPE supply chain which has been reliant on overseas-based manufacturers. Despite the urgency in demand, PPE must be properly tested for functionality and quality. We describe the establishment of local face shields manufacture in Western Australia to ensure adequate PPE for HCW. Ten thousand face shields for general use (standard) and for ear, nose and throat (ENT) specialist use were produced. Materials and design considerations are described, and the face shields were vigorously tested to the relevant Standards to ensure their effectiveness as a protective barrier, including splash and impact resistance. Comparative testing with traditional and other novel face shields was also undertaken. Therapeutic Goods Administration (TGA) licence was obtained to manufacture and supply the face shields as a Class I medical device. The swiftness of process is a credit to collaboration from industry, academia and healthcare.

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity.

Obesity is a major risk factor for Coronavirus disease (COVID-19) severity; however, the mechanisms underlying this relationship are not fully understood. As obesity influences the plasma proteome, we sought to identify circulating proteins mediating the effects of obesity on COVID-19 severity in humans. Here, we screened 4,907 plasma proteins to identify proteins influenced by body mass index using Mendelian randomization. This yielded 1,216 proteins, whose effect on COVID-19 severity was assessed, again using Mendelian randomization. We found that an s.d. increase in nephronectin (NPNT) was associated with increased odds of critically ill COVID-19 (OR = 1.71, P = 1.63 × 10-10). The effect was driven by an NPNT splice isoform. Mediation analyses supported NPNT as a mediator. In single-cell RNA-sequencing, NPNT was expressed in alveolar cells and fibroblasts of the lung in individuals who died of COVID-19. Finally, decreasing body fat mass and increasing fat-free mass were found to lower NPNT levels. These findings provide actionable insights into how obesity influences COVID-19 severity.

Surgical Treatments to Improve Visual Acuity in Infantile Nystagmus Syndrome: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the literature on the efficacy of surgical procedures to improve visual acuity (VA) in patients with infantile nystagmus syndrome (INS). METHODS: Literature searches were last conducted in January 2022 in the PubMed database for English-language studies with no date restrictions. The combined searches yielded 354 abstracts, of which 46 were reviewed in full text. Twenty-three of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: One included study was a randomized trial; the remaining 22 were case series. The 23 studies included children and adults with INS and a variable proportion with anomalous head position (AHP), strabismus, and sensory diagnoses. The surgical interventions evaluated included large recessions, tenotomy and reattachment (TAR), myectomy with or without pulley fixation, and anterior extirpation of the 4 horizontal rectus muscles, as well as various procedures to correct an AHP in which VA was reported as a secondary outcome. The data were mixed, with improvements in binocular best-corrected visual acuity (BCVA) ranging from no improvement to 0.3 logarithm of the minimum angle of resolution (logMAR), or 3 lines. (Most studies were in the range of 0.05-0.2 logMAR.) Statistically significant improvement in VA was noted in 12 of 16 studies (75%) that performed statistical analyses, with no clear advantage of any single procedure. Complications and reoperations were lowest in patients who underwent TAR and highest in those who underwent myectomy or anterior extirpation. CONCLUSIONS: The best available evidence suggests that eye muscle surgery in patients with INS results in a modest improvement in VA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000-2014 (CONCORD-3).

BACKGROUND: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. METHODS: We analyzed individual data for adults (15-99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000-2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. RESULTS: The study included 556,237 adults. In 2010-2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%-38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000-2004 and 2005-2009. These improvements were more noticeable among adults diagnosed aged 40-70 years than among younger adults. CONCLUSIONS: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines.

Shifting incidence and survival of epithelial ovarian cancer (1995-2014): A SurvMark-2 study.

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom). Data on invasive EOC diagnosed in women aged 15 to 99 years during 1995 to 2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995 and 2014 among women aged 65 to 99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma "not otherwise specified" with estimates ranging between 4.4% and 7.4% in women aged 15 to 64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival.

Refractive Growth of the Crystalline Lens in the Infant Aphakia Treatment Study.

Objective: To compare the rate of refractive growth (RRG3) of the crystalline lens ("lens") versus the eye excluding the lens ("globe") for the fellow, noncataractous eyes of participants in the Infant Aphakia Treatment Study. Design: Retrospective cohort study. Subjects: A total of 114 children who had unilateral cataract surgery as infants were recruited. Biometric and refraction data were obtained from the normal eyes at surgery and at 1, 5, and 10 years. Subjects were included if complete data (axial length [AL], corneal power, and refraction) were available at surgery and at 10 years of age. Methods: At surgery and at 1, 5, and 10 years, AL, corneal power, and cycloplegic refraction were measured in the normal eyes. For each eye, the RRG3 was defined by linear regression of refraction at the intraocular lens (IOL) plane against log10 (age + 0.6 years). The RRG3 for the globe was based on IOL power for emmetropia; the RRG3 for the lens was based on IOL power calculated to give the observed refractions. Intraocular lens powers were calculated with the Holladay 1 formula. The means were compared with a paired 2-tailed t test, and linear regression was used to look for a correlation between RRG3 of the lens globe. Main Outcome Measures: The RRG3 of the lens and globe. Results: Complete data were available for 107 normal eyes. The mean RRG3 of the lenses was -12.0 ± 2.5 diopters (D) and the mean RRG3 of the globes was -14.1 ± 2.7 D (P < 0.001). The RRG3 of the lens correlated with the RRG3 of the globe (R 2  = 0.25, P < 0.001). Conclusions: The RRG3 was 2 D more negative in globes compared with lenses in normal eyes. Globes with a greater rate of growth tended to have lenses with a greater rate of growth.

Reprograming of Gene Expression of Key Inflammatory Signaling Pathways in Human Peripheral Blood Mononuclear Cells by Soybean Lectin and Resveratrol.

Inflammation is linked to several human diseases like microbial infections, cancer, heart disease, asthma, diabetes, and neurological disorders. We have shown that the prototype inflammatory agonist LPS modulates the activity of Ubiquitin-Proteasome System (UPS) and regulates transcription factors such as NF-κB, leading to inflammation, tolerance, hypoxia, autophagy, and apoptosis of cells. We hypothesized that proteasome modulators resveratrol and soybean lectin would alter the gene expression of mediators involved in inflammation-induced signaling pathways, when administered ex vivo to human peripheral blood mononuclear blood cells (PBMCs) obtained from normal healthy controls. To test this hypothesis, analysis of RNA derived from LPS-treated human PBMCs, with or without resveratrol and soybean lectin, was carried out using Next Generation Sequencing (NGS). Collectively, the findings described herein suggest that proteasome modulators, resveratrol (proteasome inhibitor) and lectins (proteasome activator), have a profound capacity to modulate cytokine expression in response to proteasome modulators, as well as expression of mediators in multiple signaling pathways in PBMCs of control subjects. We show for the first-time that resveratrol downregulates expression of mediators involved in several key signaling pathways IFN-γ, IL-4, PSMB8 (LMP7), and a subset of LPS-induced genes, while lectins induced IFN-γ, IL-4, PSMB8, and many of the same genes as LPS that are important for innate and adaptive immunity. These findings suggest that inflammation may be influenced by common dietary components and this knowledge may be used to prevent or reverse inflammation-based diseases.