Search

Deep learning may detect biologically important signals embedded in tumor morphologic features that confer distinct prognoses. Tumor morphologic features were quantified to enhance patient risk stratification within DNA mismatch repair (MMR) groups using deep learning. Using a quantitative segmentation algorithm (QuantCRC) that identifies 15 distinct morphologic features, we analyzed 402 resected stage III colon carcinomas [191 deficient (d)-MMR; 189 proficient (p)-MMR] from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy. Results were validated in an independent cohort (176 d-MMR; 1,094 p-MMR). Association of morphologic features with clinicopathologic variables, MMR, KRAS, BRAFV600E, and time-to-recurrence (TTR) was determined. Multivariable Cox proportional hazards models were developed to predict TTR. Tumor morphologic features differed significantly by MMR status. Cancers with p-MMR had more immature desmoplastic stroma. Tumors with d-MMR had increased inflammatory stroma, epithelial tumor-infiltrating lymphocytes (TIL), high-grade histology, mucin, and signet ring cells. Stromal subtype did not differ by BRAFV600E or KRAS status. In p-MMR tumors, multivariable analysis identified tumor-stroma ratio (TSR) as the strongest feature associated with TTR [HRadj 2.02; 95% confidence interval (CI), 1.14-3.57; P = 0.018; 3-year recurrence: 40.2% vs. 20.4%; Q1 vs. Q2-4]. Among d-MMR tumors, extent of inflammatory stroma (continuous HRadj 0.98; 95% CI, 0.96-0.99; P = 0.028; 3-year recurrence: 13.3% vs. 33.4%, Q4 vs. Q1) and N stage were the most robust prognostically. Association of TSR with TTR was independently validated. In conclusion, QuantCRC can quantify morphologic differences within MMR groups in routine tumor sections to determine their relative contributions to patient prognosis, and may elucidate relevant pathophysiologic mechanisms driving prognosis., Significance: A deep learning algorithm can quantify tumor morphologic features that may reflect underlying mechanisms driving prognosis within MMR groups. TSR was the most robust morphologic feature associated with TTR in p-MMR colon cancers. Extent of inflammatory stroma and N stage were the strongest prognostic features in d-MMR tumors. TIL density was not independently prognostic in either MMR group., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Purpose: There is a need to improve current risk stratification of stage II colorectal cancer to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines., Experimental Design: ASCO and QuantCRC-integrated schemes were applied to a cohort of 398 mismatch-repair proficient (MMRP) stage II colorectal cancers from three large academic medical centers. The ASCO stage II scheme was taken from recent guidelines. The QuantCRC-integrated scheme utilized pT3 versus pT4 and a QuantCRC-derived risk classification. Evaluation of recurrence-free survival (RFS) according to these risk schemes was compared using the log-rank test and HR., Results: Integration of QuantCRC provides improved risk stratification compared with the ASCO scheme for stage II MMRP colorectal cancers. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared with the ASCO scheme (62.5% vs. 42.2%) without compromising excellent 3-year RFS. The QuantCRC-integrated scheme provided larger HR for both intermediate-risk (2.27; 95% CI, 1.32-3.91; P = 0.003) and high-risk (3.27; 95% CI, 1.42-7.55; P = 0.006) groups compared with ASCO intermediate-risk (1.58; 95% CI, 0.87-2.87; P = 0.1) and high-risk (2.24; 95% CI, 1.09-4.62; P = 0.03) groups. The QuantCRC-integrated risk groups remained prognostic in the subgroup of patients that did not receive any adjuvant chemotherapy., Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance for stage II MMRP colorectal cancers., (©2024 American Association for Cancer Research.)

The sustained instability in Afghanistan, along with ongoing disease outbreaks and the impact of the COVID-19 pandemic, has significantly affected the country.During the COVID-19 pandemic, the country's detection and response capacities faced challenges. Case identification was done in all health facilities from primary to tertiary levels but neglected cases at the community level, resulting in undetected and uncontrolled transmission from communities. This emphasizes a missed opportunity for early detection that Event-Based Surveillance (EBS) could have facilitated.Therefore, Afghanistan planned to strengthen the EBS component of the national public health surveillance system to enhance the capacity for the rapid detection and response to infectious disease outbreaks, including COVID-19 and other emerging diseases. This effort was undertaken to promptly mitigate the impact of such outbreaks.We conducted a landscape assessment of Afghanistan's public health surveillance system to identify the best way to enhance EBS, and then we crafted an implementation work plan. The work plan included the following steps: establishing an EBS multisectoral coordination and working group, identifying EBS information sources, prioritizing public health events of importance, defining signals, establishing reporting mechanisms, and developing standard operating procedures and training guides.EBS is currently being piloted in seven provinces in Afghanistan. The lessons learned from the pilot phase will support its overall expansion throughout the country., (© 2024. The Author(s).)

Event-based surveillance (EBS) systems have been implemented globally to support early warning surveillance across human, animal, and environmental health in diverse settings, including at the community level, within health facilities, at border points of entry, and through media monitoring of internet-based sources. EBS systems should be evaluated periodically to ensure that they meet the objectives related to the early detection of health threats and to identify areas for improvement in the quality, efficiency, and usefulness of the systems. However, to date, there has been no comprehensive framework to guide the monitoring and evaluation of EBS systems; this absence of standardisation has hindered progress in the field. The Africa Centres for Disease Control and Prevention and US Centers for Disease Control and Prevention have collaborated to develop an EBS monitoring and evaluation indicator framework, adaptable to specific country contexts, that uses measures relating to input, activity, output, outcome, and impact to map the processes and expected results of EBS systems. Through the implementation and continued refinement of these indicators, countries can ensure the early detection of health threats and improve their ability to measure and describe the impacts of EBS systems, thus filling the current evidence gap regarding their effectiveness., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

With the increasing aging population there is a need for more gerontological social work practitioners; however, such training for social workers in Canada is limited. To help address this gap, one faculty of social work developed a graduate level clinical social work practice certificate with a specialization in gerontology. In this paper we explore students' and instructors' perspectives about the curriculum, delivery, and impact of this certificate, and provide recommendations for improvement, particularly with respect to the clinical nature of the courses. Eight students and four instructors participated in the study. Strengths and opportunities for enhancement were identified for curriculum and delivery. Study findings also indicated that further curriculum development should focus on enhancing clinical skill development and providing more practice experience. Implications arising from these findings included developing clinical skills through experiential learning, interprofessional education, and service learning.

Tumor budding (TB) is a powerful prognostic factor in colorectal cancer (CRC). An internationally standardized method for its assessment (International Tumor Budding Consensus Conference [ITBCC] method) has been adopted by most CRC pathology protocols. This method requires that TB counts are reported by field area (0.785 mm 2 ) rather than objective lens and a normalization factor is applied for this purpose. However, the validity of this approach is yet to be tested. We sought to validate the ITBCC method with a particular emphasis on normalization as a tool for standardization. In a cohort of 365 stage I-III CRC, both normalized and non-normalized TB were significantly associated with disease-specific survival and recurrence-free survival ( P <0.0001). Examining both 0.95 and 0.785 mm 2 field areas in a subset of patients (n=200), we found that normalization markedly overcorrects TB counts: Counts obtained in a 0.95 mm 2 hotspot field were reduced by an average of 17.5% following normalization compared with only 3.8% when counts were performed in an actual 0.785 mm 2 field. This resulted in 45 (11.3%) cases being downgraded using ITBCC grading criteria following normalization, compared with only 5 cases (1.3%, P =0.0007) downgraded when a true 0.785 mm 2 field was examined. In summary, the prognostic value of TB was retained regardless of whether TB counts in a 0.95 mm 2 field were normalized. Normalization resulted in overcorrecting TB counts with consequent downgrading of most borderline cases. This has implications for risk stratification and adjuvant treatment decisions, and suggests the need to re-evaluate the role of normalization in TB assessment., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Venous invasion (VI) is a powerful yet under-reported prognostic factor in colorectal cancer (CRC). Efforts to improve its detection have largely focused upon histological assessment, with less attention paid to tissue-sampling strategies. This study aimed to prospectively determine the number of tumour blocks required to optimise VI detection in CRC resections. In addition, the relationship between linear spiculation (LS) and extramural venous invasion (EMVI) was investigated., Methods and Results: A standardised tissue sampling protocol was developed and applied prospectively to 217 CRC resections [AJCC 8th edition, stage 1 (n = 32); stage 2 (n = 84); stage 3 (n = 87); stage 4 (n = 14); and post-neoadjuvant therapy (n = 46)]. Elastin stains were performed on all tumour blocks. VI was identified in 55% of cases (EMVI = 37%; IMVI alone = 18%). The sensitivity of VI detection increased with increasing numbers of tumour blocks submitted [one block (35%), three blocks (66%), five blocks (84%), six blocks (95%) and seven blocks (97%)]. Similar findings were observed for EMVI [one block (35%), three blocks (73%), five blocks (89%), six blocks (96%) and seven blocks (96%)]. LS was identified macroscopically in 22% of specimens. In cases where no neoadjuvant therapy had been given, EMVI was significantly associated with LS (71% in LS+ cases versus 29% in LS- cases; P < 0.001). In addition, tumour blocks targeting LS were associated with a fivefold higher rate of EMVI compared with blocks that did not (P < 0.001)., Conclusions: Our findings demonstrate the impact of tissue sampling and quality of gross examination on VI detection and may inform practices in future CRC protocols., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Hypertension is a risk factor for major cardiovascular events and it is usually detected and managed by general medical practitioners (GPs) in primary care. However, it is estimated that 4.8 million adults are living with untreated high blood pressure (BP) in the UK. Health authorities are encouraging more collaborative work across health professions to find and refer individuals with undiagnosed hypertension. In this case, in 2022, a 65-year-old man with a previous history of hypertension, taking antihypertensive medication, attended a BP clinic at the University of Plymouth, Peninsula Dental School as part of a hypertension case finding pilot. His systolic and diastolic BP were 150 and 85 mmHg, respectively, and as per the trial protocol, a referral letter was sent to his GP for suspected further assessment and investigation. Then, an onward referral was made to secondary care and the participant was subsequently hospitalised for 13 days for treatment of heart failure and suspected acute coronary syndrome. This case report highlights that BP readings taken in a primary care dental setting can be very useful and recommends better integration of dental services into primary care to reduce the risk of major cardiovascular events., (© 2023. The Author(s), under exclusive licence to the British Dental Association.)

Purpose: Patient education is one of the important components of reducing the morbidity of osteoporosis. The aim of this study is to validate the Hindi version of the Osteoporosis Knowledge Assessment Tool (OKAT-H) among a hospital-based sample in the age group of 18-44 years of age., Methods: The study was conducted in two phases - translation and adaption of the OKAT in Hindi followed by its validation. The translated tool was analyzed by Flesch reading ease, McNemar test, Cronbach alpha, difficulty index, discrimination index, and principal factor analysis., Results: Two hundred and sixty women with a mean age of 28.3 ± 17.2 years were enrolled in the study. The mean score of the OKAT-H tool obtained in the study was 11.3 ± 2.1. A significant difference was noted in the scores based on educational qualification or with any family history of either osteoporosis or fracture ( P < 0.05). The Flesch score for the OKAT-H tool was 86. Inter-item correlation for all the items ranged between 0.15 and 0.5. The Cronbach's alpha measured 0.892 suggesting high internal consistency. Items number 6, 7, 8, 9, 13, and 14 showed a significant difference on the McNemar test questioning its consistency on test-retest., Conclusion: A new shorter version of the tool may be developed since six items showed low consistency. The use of such an instrument in local language would help spread awareness about the disease as well as help the population in adopting osteoprotective strategies and also to seek help and advice regarding treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Mid-life Health.)

Purpose: Intra-operative traction (IOT) has emerged as new modality for improving correction rates in scoliosis since it has the potential to reduce operative time and blood loss in neuromuscular scoliosis (NMS). The aim of this study is to describe the effects of IOT in deformity correction in NMS., Methods: The search was conducted in online electronic databases following the PRISMA guidelines. This review included studies on NMS which have described usage of IOT in deformity correction., Results: Eight studies were included in analysis and review. There was low-to-moderate heterogeneity across the studies (I 2 - 42.4 to 93.9%). All the studies used cranio-femoral traction for IOT. The final Cobb's angle in coronal plane was significantly lower in the traction group as compared to the non-traction group (SMD - 0.36 95% CI - 0.71 to 0). There was a trend towards better outcomes in final obliquity (SMD - 0.78 95% CI - 1.64 to 0.09), operative time (SMD - 1.09 95% CI - 2.25 to 0.08) and blood loss (SMD - 0.86 95% CI significantly lower in the traction group as 2.15 to 0.44) but did not reach statistical significance., Conclusion: IOT helped to achieve significant scoliotic curve correction in NMS compared to non-traction group. Despite the overall tendency of improved pelvic obliquity correction, reduced operative time and reduced blood loss as compared to a surgery without the use of IOT, it did not achieve statistical significance. Further studies which are prospective with a larger sample size and focussing on a particular etiology may be conducted which would validate the results., Level of Evidence: IV., (© 2023. The Author(s), under exclusive licence to Scoliosis Research Society.)

Mast cells are residents of the tubular gastrointestinal (GI) tract, where they play an important role in host defence and other vital functions. Dysregulation of mast cells has been implicated in the pathogenesis of several neoplastic, inflammatory, and functional disorders, some of which may manifest with GI symptoms. Surgical pathologists must therefore confront when and how to evaluate GI biopsies for mast cells, and whether such decisions should be based on morphologic criteria, clinical context, or direct request from clinical colleagues. The pathologist's role in evaluation of mast cell infiltrates is best defined in the diagnosis of systemic mastocytosis, where the utility of morphologic assessment coupled with ancillary studies is well established. In contrast, in nonneoplastic mast cell disorders such as mast cell activation syndrome, irritable bowel syndrome, or so-called 'mastocytic enterocolitis', a role for histopathology, if any, is controversial. Despite this, pathologists have seen a sharp increase in requests for mast cell quantification in the latter setting, despite these requests not being supported by published evidence. Moreover, what constitutes a 'normal' number of mast cells in a luminal GI biopsy is not well established. As a result, there is considerable variation in how these requests are handled in practice. This review evaluates and summarizes the published evidence relating to mast cell evaluation in endoscopic GI biopsies in various clinical scenarios, with a goal of providing practical, evidence-based guidance for the surgical pathologist when approached with requests for mast cell quantification in GI biopsies., (© 2023 John Wiley & Sons Ltd.)

Background: National Health Service (NHS) strategies in the United Kingdom (UK) have highlighted the need to maximise case-finding opportunities by improving coverage in non-traditional settings with the aim of reducing delayed diagnosis of non-communicable diseases. Primary care dental settings may also help to identify patients., Methods: Case-finding appointments took place in a primary care dental school. Measurements of blood pressure, body mass index (BMI), cholesterol, glucose and QRisk were taken along with a social/medical history. Participants with high cardiometabolic risk were referred to their primary care medical general practitioner (GP) and/or to local community health self-referral services, and followed up afterwards to record diagnosis outcome., Results: A total of 182 patients agreed to participate in the study over a 14-month period. Of these, 123 (67.5%) attended their appointment and two participants were excluded for age. High blood pressure (hypertension) was detected in 33 participants, 22 of whom had not been previous diagnosed, and 11 of whom had uncontrolled hypertension. Of the hypertensive individuals with no previous history, four were confirmed by their GP. Regarding cholesterol, 16 participants were referred to their GP for hypercholesterolaemia: 15 for untreated hypercholesterolaemia and one for uncontrolled hypercholesterolaemia., Conclusions: Case-finding for hypertension and identifying cardiovascular risk factors has high acceptability in a primary dental care setting and supported by confirmational diagnoses by the GP.

Context.—: Resident physicians face a higher rate of burnout and depression than the general population. Few studies have examined burnout and depression in Canadian laboratory medicine residents, and none during the COVID-19 pandemic., Objective.—: To identify the prevalence of burnout and depression, contributing factors, and the impact of COVID-19 in this population., Design.—: An electronic survey was distributed to Canadian laboratory medicine residents. Burnout was assessed using the Oldenburg Burnout Inventory. Depression was assessed using the Patient Health Questionnaire 9., Results.—: Seventy-nine responses were collected. The prevalence of burnout was 63% (50 of 79). The prevalence of depression was 47% (37 of 79). Modifiable factors significantly associated with burnout included career dissatisfaction, below average academic performance, lack of time off for illness, stress related to finances, lack of a peer or staff physician mentor, and a high level of fatigue. Modifiable factors significantly associated with depression further included a lack of access to wellness resources, lack of time off for leisure, and fewer hours of sleep. Fifty-five percent (41 of 74) of participants reported direct impacts to their personal circumstances by the COVID-19 pandemic., Conclusions.—: Burnout and depression are significant issues affecting Canadian laboratory medicine residents. As the COVID-19 pandemic continues, we recommend the institution of flexible work arrangements, protected time off for illness and leisure, ongoing evaluation of career satisfaction, formal and informal wellness programming with trainee input, formal mentorship programming, and a financial literacy curriculum as measures to improve trainee wellness.

In 2016, Tanzania expanded sentinel surveillance for influenza-like illness (ILI) and severe acute respiratory infection (SARI) to include testing for non-influenza respiratory viruses (NIRVs) and additional respiratory pathogens at 9 sentinel sites. During 2017-2019, respiratory specimens from 2730 cases underwent expanded testing: 2475 specimens (90.7%) were tested using a U.S. Centers for Disease Control and Prevention (CDC)-developed assay covering 7 NIRVs (respiratory syncytial virus [RSV], rhinovirus, adenovirus, human metapneumovirus, parainfluenza virus 1, 2, and 3) and influenza A and B viruses. Additionally, 255 specimens (9.3%) were tested using the Fast-Track Diagnostics Respiratory Pathogens 33 (FTD-33) kit which covered the mentioned viruses and additional viral, bacterial, and fungal pathogens. Influenza viruses were identified in 7.5% of all specimens; however, use of the CDC assay and FTD-33 kit increased the number of specimens with a pathogen identified to 61.8% and 91.5%, respectively. Among the 9 common viruses between the CDC assay and FTD-33 kit, the most identified pathogens were RSV (22.9%), rhinovirus (21.8%), and adenovirus (14.0%); multi-pathogen co-detections were common. Odds of hospitalization (SARI vs. ILI) varied by sex, age, geographic zone, year of diagnosis, and pathogen identified; hospitalized illnesses were most common among children under the age of 5 years. The greatest number of specimens were submitted for testing during December-April, coinciding with rainy seasons in Tanzania, and several viral pathogens demonstrated seasonal variation (RSV, human metapneumovirus, influenza A and B, and parainfluenza viruses). This study demonstrates that expanding an existing influenza platform to include additional respiratory pathogens can provide valuable insight into the etiology, incidence, severity, and geographic/temporal patterns of respiratory illness. Continued respiratory surveillance in Tanzania, and globally, can provide valuable data, particularly in the context of emerging respiratory pathogens such as SARS-CoV-2, and guide public health interventions to reduce the burden of respiratory illnesses., Competing Interests: The authors declare that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background & Aims: To examine whether quantitative pathologic analysis of digitized hematoxylin and eosin slides of colorectal carcinoma (CRC) correlates with clinicopathologic features, molecular alterations, and prognosis., Methods: A quantitative segmentation algorithm (QuantCRC) was applied to 6468 digitized hematoxylin and eosin slides of CRCs. Fifteen parameters were recorded from each image and tested for associations with clinicopathologic features and molecular alterations. A prognostic model was developed to predict recurrence-free survival using data from the internal cohort (n = 1928) and validated on an internal test (n = 483) and external cohort (n = 938)., Results: There were significant differences in QuantCRC according to stage, histologic subtype, grade, venous/lymphatic/perineural invasion, tumor budding, CD8 immunohistochemistry, mismatch repair status, KRAS mutation, BRAF mutation, and CpG methylation. A prognostic model incorporating stage, mismatch repair, and QuantCRC resulted in a Harrell's concordance (c)-index of 0.714 (95% confidence interval [CI], 0.702-0.724) in the internal test and 0.744 (95% CI, 0.741-0.754) in the external cohort. Removing QuantCRC from the model reduced the c-index to 0.679 (95% CI, 0.673-0.694) in the external cohort. Prognostic risk groups were identified, which provided a hazard ratio of 2.24 (95% CI, 1.33-3.87, P = .004) for low vs high-risk stage III CRCs and 2.36 (95% CI, 1.07-5.20, P = .03) for low vs high-risk stage II CRCs, in the external cohort after adjusting for established risk factors. The predicted median 36-month recurrence rate for high-risk stage III CRCs was 32.7% vs 13.4% for low-risk stage III and 15.8% for high-risk stage II vs 5.4% for low-risk stage II CRCs., Conclusions: QuantCRC provides a powerful adjunct to routine pathologic reporting of CRC. A prognostic model using QuantCRC improves prediction of recurrence-free survival., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Tumor budding (TB) and poorly differentiated clusters (PDCs) are powerful prognostic factors in colorectal cancer (CRC). Despite their morphologic and biological overlap, TB and PDC are assessed separately and are distinguished by an arbitrary cutoff for cell cluster size. This cutoff can be challenging to apply in practice and its biological significance remains unclear. We developed a novel scoring system that incorporates TB and PDC into a single parameter ("Combined Score"; CS), eliminating the need for such cutoffs and allowing the prognostic value of PDC to be captured alongside TB. In a cohort of 481 stage I-III CRC resections, CS was significantly associated with American Joint Committee on Cancer (AJCC) stage, T-stage, N-stage, histologic grade, tumor deposits, lymphovascular invasion, and perineural invasion ( P &lt;0.0001). In addition, CS was significantly associated with decreased 5-year recurrence-free survival, overall survival, and disease-specific survival ( P &lt;0.0001). TB and PDC showed similar associations with oncologic outcomes, with hazard ratios consistently lower than for CS. The association between CS and oncologic outcomes remained significant in subgroup analyses stratified by AJCC stage, anatomic location (rectum/colon) and neoadjuvant therapy status. On multivariable analysis, CS retained its significant association with oncologic outcomes ( P =0.0002, 0.005, and 0.009) for recurrence-free survival, disease-specific survival, and overall survival, respectively. In conclusion, CS provides powerful risk stratification in CRC which is at least equivalent to that of TB and PDC assessed individually. If validated elsewhere, CS has practical advantages and a biological rationale that may make it an attractive alternative to assessing these features separately., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Venous invasion (VI) is a powerful yet underreported prognostic factor in colorectal cancer (CRC). Its detection can be improved with an elastin stain. We evaluated the impact of routine elastin staining on VI detection in resected CRC and its relationship with oncologic outcomes. Pathology reports from the year before (n=145) and the year following (n=128) the implementation of routine elastin staining at our institution were reviewed for established prognostic factors, including VI. A second review, using elastin stains, documented the presence/absence, location, number, and size of VI foci. The relationship between VI and oncologic outcomes was evaluated for original and review assessments. VI detection rates increased from 21% to 45% following implementation of routine elastin staining (odds ratio [OR]=3.1; 95% confidence interval [CI]: 1.8-5.3; P<0.0001). The second review revealed a lower VI miss rate postimplementation than preimplementation (22% vs. 48%, respectively; P=0.007); this difference was even greater for extramural VI-positive cases (9% vs. 38%, respectively; P=0.0003). Missed VI cases postimplementation had fewer VI foci per missed case (P=0.02) and a trend towards less extramural VI than those missed preimplementation. VI assessed with an elastin stain was significantly associated with recurrence-free survival (P=0.003), and cancer-specific survival (P=0.01) in contrast to VI assessed on hematoxylin and eosin alone (P=0.053 and 0.1, respectively). The association between VI and hematogenous metastasis was far stronger for elastin-detected VI (OR=11.5; 95% CI: 3.4-37.1; P<0.0001) than for hematoxylin and eosin-detected VI (OR=3.7; 95% CI: 1.4-9.9; P=0.01). Routine elastin staining enhances VI detection and its ability to stratify risk in CRC and should be considered for evaluation of CRC resection specimens., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Venous invasion (VI) is a powerful prognostic factor in colorectal cancer (CRC) that is widely underreported. The ability of elastin stains to improve VI detection is now recognized in several international CRC pathology protocols. However, concerns related to the cost and time required to perform and evaluate these stains in addition to routine hematoxylin and eosin (H&E) stains remains a barrier to their wider use. We therefore sought to determine whether an elastin trichrome (ET) stain could be used as a "stand-alone" stain in CRC resections, by comparing the sensitivity, accuracy, and reproducibility of detection of CAP-mandated prognostic factors using ET and H&E stains. Representative H&E- and ET-stained slides from 50 CRC resections, including a representative mix of stages and prognostic factors, were used to generate 2 study sets. Each case was represented by H&E slides in 1 study set and by corresponding ET slides from the same blocks in the other study set. Ten observers (3 academic gastrointestinal [GI] pathologists, 4 community pathologists, 3 fellows) evaluated each study set for CAP-mandated prognostic factors. ET outperformed H&E in the assessment of VI with respect to detection rates (50% vs. 28.6%; P<0.0001), accuracy (82% vs. 59%, P<0.0001), and reproducibility (k=0.554 vs. 0.394). No significant differences between ET and H&E were observed for other features evaluated. In a poststudy survey, most observers considered the ease and speed of assessment at least equivalent for ET and H&E for most prognostic factors, and felt that ET would be feasible as a stand-alone stain in practice. If validated by others, our findings support the use of ET, rather than H&E, as the primary stain for the evaluation of CRC resections., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To develop and validate a deep learning algorithm to quantify a broad spectrum of histological features in colorectal carcinoma., Methods and Results: A deep learning algorithm was trained on haematoxylin and eosin-stained slides from tissue microarrays of colorectal carcinomas (N = 230) to segment colorectal carcinoma digitised images into 13 regions and one object. The segmentation algorithm demonstrated moderate to almost perfect agreement with interpretations by gastrointestinal pathologists, and was applied to an independent test cohort of digitised whole slides of colorectal carcinoma (N = 136). The algorithm correctly classified mucinous and high-grade tumours, and identified significant differences between mismatch repair-proficient and mismatch repair-deficient (MMRD) tumours with regard to mucin, inflammatory stroma, and tumour-infiltrating lymphocytes (TILs). A cutoff of >44.4 TILs per mm 2 carcinoma gave a sensitivity of 88% and a specificity of 73% in classifying MMRD carcinomas. Algorithm measures of tumour budding (TB) and poorly differentiated clusters (PDCs) outperformed TB grade derived from routine sign-out, and compared favourably with manual counts of TB/PDCs with regard to lymphatic, venous and perineural invasion. Comparable associations were seen between algorithm measures of TB/PDCs and manual counts of TB/PDCs for lymph node metastasis (all P < 0.001); however, stronger correlations were seen between the proportion of positive lymph nodes and algorithm measures of TB/PDCs. Stronger associations were also seen between distant metastasis and algorithm measures of TB/PDCs (P = 0.004) than between distant metastasis and TB (P = 0.04) and TB/PDC counts (P = 0.06)., Conclusions: Our results highlight the potential of deep learning to identify and quantify a broad spectrum of histological features in colorectal carcinoma., (© 2021 John Wiley & Sons Ltd.)

What Is Known and Objective: Delirium has been associated with increased mortality and prolonged hospital length of stay among critical care patients. Furthermore, treatment of delirium remains variable amongst clinicians due to limited evidence. The objective of this study was to determine the local incidence of delirium and to characterize the effectiveness and safety of pharmacological therapy used to treat delirium., Methods: A retrospective chart review evaluated patients diagnosed with delirium (Intensive Care Delirium Screening Checklist score ≥4) and requiring mechanical ventilation for ≥48 hours from January 2016 to June 2017. The primary outcomes included comparison of resolution, the time to first resolution and recurrence of delirium in patients prescribed pharmacological and/or pre-emptive therapy versus those who did not. Secondary outcomes included incidence of adverse effects of drug therapy and delirium attributable adverse events., Results and Discussion: The incidence of delirium during our defined study period was 49%. Of the 178 patients included in the study, 136 (76%) received drug therapy for delirium. Agents used for treatment of delirium included dexmedetomidine (n = 90 [66%]), haloperidol (n = 77 [57%]), and quetiapine (n = 74 [54%]). Resolution of delirium occurred in 94 (52%) of patients and the difference was statistically significant favoring patients who did not receive pharmacological therapy. There was no difference in the median time to resolution of delirium (3 days) for patients who received pharmacological and/or pre-emptive therapy versus those who did not. Bradycardia and hypotension were the most frequently documented medication-related adverse events. Self-removal of an invasive line/catheter, was reported in 36 (26%) patients despite receiving pharmacological treatment., What Is New and Conclusion: Despite unclear evidence that pharmacological interventions help with delirium management, the majority of our patients received such interventions. To improve patient outcomes, we should shift focus towards non-pharmacological interventions for delirium., (© 2020 John Wiley & Sons Ltd.)

Poorly differentiated clusters (PDC), defined as small groups of ≥5 tumour cells without glandular differentiation, have gained recent attention as a promising prognostic factor in colorectal cancer (CRC). Numerous studies have shown PDC to be significantly associated with other adverse histopathological features and worse clinical outcomes. PDC may hold particular promise in stage II colon cancer, where risk stratification plays a critical role in patient selection for adjuvant chemotherapy. In addition, emerging evidence suggests that PDC can predict lymph node metastasis in endoscopically resected pT1 CRC, potentially helping the selection of patients for oncological resection. In 'head-to-head' comparisons, PDC grade has consistently outperformed conventional histological grading systems both in terms of risk stratification and reproducibility. With a number of large-scale studies now available, this review evaluates the evidence regarding the prognostic significance of PDC, considers its relationship with other emerging invasive front prognostic markers (such as tumour budding and stroma type), assesses its 'practice readiness', addressing issues such as interobserver reproducibility, scoring methodologies and special histological subtypes (e.g. micropapillary and mucinous carcinoma), and draws attention to ongoing challenges and areas in need of further study. Finally, emerging data on the role of PDC in non-colorectal cancers are briefly considered., (© 2020 John Wiley & Sons Ltd.)

Concussions represent a major concern for hockey teams. During one winter season, all players on two Junior Hockey Teams were assessed in order to establish an incidence baseline for concussions. The qEEG was utilized as it measures the probability of concussion and its severity. The SCL 90-R and CNS questionnaire were used to provide insight into various aspects of cognitive functioning. Results indicated that of the players assessed (N = 46) approximately two-thirds (N = 32) tested positive for concussions. A minority of the concussions were assessed as mild (N = 13), while 19 were assessed as moderately severe. The most common sites indicated as injured were F8 and T6 (right side of head) and O1 and O2 (back of head) and F7 (left front of head). A comparison of the questionnaire results to expected behavioural issues are discussed. This appears to be one of the first studies of junior hockey players using an objective measure of study (qEEG).

Purpose: The Stollery Children's Hospital serves a very large geographic region of over at least 650,000 km² with patients from outside of Edmonton accounting for approximately 50% of the service population. The aim of this study is to document the experience and opinion of the patient and clinician satisfaction with telehealth encounter for various pediatric surgical consultations and follow-up as a way to bridge the distance gap., Methods: We observe our experience with recent telehealth implementation from 2008 to 2009. Qualitative data were collected through questionnaires aimed at patients and clinicians., Results: There were 259 pediatric surgical telehealth encounters, of which 37% were from outside the province. There were 42 antenatal multidisciplinary, 13 chronic pain, 103 general surgery, 2 orthopedic, 63 urology, 33 head and shape nurse practioner clinic, and 3 neurosurgery consults. 83 patient and 12 clinician questionnaires were completed. 97% of patients and 73% of clinicians reported satisfaction with having a telehealth session. 97% of the patients reside more than 200 km from the city and 77% live more than 400 km away. 48% reported a cost saving >$500-$700., Conclusion: Telehealth for pediatric surgical services is an alternative as an acceptable, effective, and appropriate way to consult and follow-up pediatric patients who live in significantly remote areas with great clinician and patient satisfaction.

Several transcription factors are essential determinants of a cortical projection neuron identity, but their mode of action (instructive versus permissive) and downstream genetic cascades remain poorly defined. Here, we demonstrate that the proneural basic helix-loop-helix (bHLH) gene Ngn2 instructs a partial cortical identity when misexpressed in ventral telencephalic progenitors, inducing ectopic marker expression in a defined temporal sequence, including early (24 h; Nscl2), intermediate (48 h; BhlhB5), and late (72 h; NeuroD, NeuroD2, Math2, and Tbr1) target genes. Strikingly, cortical gene expression was much more rapidly induced by Ngn2 in the dorsal telencephalon (within 12 to 24 h). We identify the bHLH gene Math3 as a dorsally restricted Ngn2 transcriptional target and cofactor, which synergizes with Ngn2 to accelerate target gene transcription in the cortex. Using a novel in vivo luciferase assay, we show that Ngn2 generates only approximately 60% of the transcriptional drive in ventral versus dorsal telencephalic domains, an activity that is augmented by Math3, providing a mechanistic basis for regional differences in Ngn2 function. Cortical bHLH genes thus cooperate to control transcriptional strength, thereby temporally coordinating downstream gene expression.