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Despite marked advancements in the recognition and diagnosis of spontaneous coronary artery dissection (SCAD) over the past decade, knowledge of the basic pathophysiologic mechanisms of disease, contributing factors, and treatment continue to be poorly understood. We describe significant research gaps in our knowledge of SCAD and introduce strategies including the role of patient advocacy, independent registries, and creation of diverse centers of excellence to bridge the gap in clinical care, research, and outcomes. Lastly, we introduce an innovative patient-centered clinical care and research framework established through the SCAD Alliance and International Spontaneous Coronary Artery Dissection registry as a model for advancing knowledge of SCAD.

OBJECTIVES:. Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults. DESIGN:. Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study. SETTING:. Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021. PATIENTS/SUBJECTS:. Patients younger than 25 years receiving CRRT for acute kidney injury and/or fluid overload and requiring vasopressors. Patients receiving vasopressin were compared with patients receiving only norepinephrine/epinephrine. The impact of timing of vasopressin relative to CRRT start was assessed by categorizing patients as: early (on or before day 0), intermediate (days 1–2), and late (days 3–7). INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 1016 patients, 665 (65%) required vasopressors in the first week of CRRT. Of 665, 248 (37%) received vasopressin, 473 (71%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (death, renal replacement therapy dependence, and/or > 125% increase in serum creatinine from baseline 90 days from CRRT initiation), and 195 (29%) liberated from CRRT on the first attempt within 28 days. Receipt of vasopressin was associated with higher odds of MAKE-90 (adjusted odds ratio [aOR], 1.80; 95% CI, 1.20–2.71; p = 0.005) but not liberation success. In the vasopressin group, intermediate/late initiation was associated with higher odds of MAKE-90 (aOR, 2.67; 95% CI, 1.17–6.11; p = 0.02) compared with early initiation. CONCLUSIONS:. Nearly two-thirds of children and young adults receiving CRRT required vasopressors, including over one-third who received vasopressin. Receipt of vasopressin was associated with more MAKE-90, although earlier initiation in those who received it appears beneficial. Prospective studies are needed to understand the appropriate timing, dose, and subpopulation for use of vasopressin.

Women are disproportionately affected by symptoms of angina with nonobstructive coronary arteries (ANOCA) which is associated with significant mortality and economic impact. Although distinct endotypes of ANOCA have been defined, it is underdiagnosed and is often incompletely characterized when identified. Patients are often unresponsive to traditional therapeutic options, which are typically antianginal, and the current ability to guide treatment modification by specific pathways is limited. Studies have associated specific genetic loci, transcriptomic features, and biomarkers with ANOCA. Such panomic data, in combination with known imaging and invasive diagnostic techniques, should be utilized to define more precise pathophysiologic subtypes of ANOCA in women, which will in turn help to identify targeted, effective therapies. A precision medicine-based approach to managing ANOCA incorporating these techniques in women has the potential to significantly improve their clinical care.

Introduction: This study investigates the associations between built environment features and 3-year BMI trajectories in children and adolescents. Methods: This retrospective cohort study utilized electronic health records of individuals aged 5–18 years living in King County, Washington, from 2005 to 2017. Built environment features such as residential density; counts of supermarkets, fast-food restaurants, and parks; and park area were measured using SmartMaps at 1,600-meter buffers. Linear mixed-effects models performed in 2022 tested whether built environment variables at baseline were associated with BMI change within age cohorts (5, 9, and 13 years), adjusting for sex, age, race/ethnicity, Medicaid, BMI, and residential property values (SES measure). Results: At 3-year follow-up, higher residential density was associated with lower BMI increase for girls across all age cohorts and for boys in age cohorts of 5 and 13 years but not for the age cohort of 9 years. Presence of fast food was associated with higher BMI increase for boys in the age cohort of 5 years and for girls in the age cohort of 9 years. There were no significant associations between BMI change and counts of parks, and park area was only significantly associated with BMI change among boys in the age cohort of 5 years. Conclusions: Higher residential density was associated with lower BMI increase in children and adolescents. The effect was small but may accumulate over the life course. Built environment factors have limited independent impact on 3-year BMI trajectories in children and adolescents.

Background: Postoperative physical therapy (PT) is a cornerstone to achieve optimal patient outcomes. Access to postoperative PT can be limited by insurance type, coverage, and cost. With copayments (CP) for PT as high as $75 per visit, PT can be costprohibitive for patients. The purpose of this study was to evaluate factors affecting PT utilization among patients that underwent shoulder surgery. Methods: A retrospective analysis was performed of 80 shoulder surgery patients with postoperative PT sessions attended at a single institution from 2017 to 2019. Patients were divided based on insurance type: private insurance (PI), and Medicare with or without supplemental insurance (MI), and CP or no copayment. Demographics, CP, total, and postoperative number of PT sessions utilized was collected and analyzed. Results: The cohort had 53 females and an average age of 62. There was no significant difference between PI and MI at baseline other than surgery performed (P = .03), older MI group (69 years vs. 56 years: P < .01), and more females in PI group (76% vs. 55%; P = .05). There was no significant difference in the number of PT sessions between groups. The PI group was more likely to have a CP (P < .01). The CP group more often had PI and significantly more total PT visits (P = .05), while the no copayment group more often had Medicare (P < .01). CP was not independently associated with a change in the number of PT visits or total PT visits. Conclusions: The utilization of PT after shoulder surgery was found to not be influenced by insurance type or CP as determined by the number of PT sessions attended. Further investigations are necessary to better understand the relationship between CP and different insurance types and develop effective strategies to increase access to PT for postoperative shoulder patients.

Background: Dupilumab is a treatment approved for uncontrolled moderate-to-severe atopic dermatitis (AD). Tropical and developing countries such as Colombia have characteristics that may impact the natural history of AD and access to medical treatments. In that sense, we aimed to describe the effectiveness and safety of dupilumab in adults with moderate to severe AD in a Colombian multicenter cohort. Methods: Multicenter descriptive study that included patients who started treatment between March 2018 and May 2020 in 6 centers. Disease severity was assessed using the following: Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). These measurements were collected according to availability at baseline, 3–5 months, 6–12 months, and more than 12 months. Days of sick leave, hospitalizations, and AD flares before and after dupilumab treatment were reported. Adverse events (AEs) were recorded during follow-up. Results: Ninety-three patients were included, with a median age of 32 years (IQR: 24.0; 40.0) and a disease evolution time of 21 years (IQR: 16.0; 29.5). 88.2% had at least 1 allergic disease other than AD. An improvement greater than or equal to 75% EASI was observed in 41.7% of patients at 3–5 months, in 73.7% of patients at 6–12 months, and in 75.0% of patients after 12 months. For those reporting SCORAD and POEM, the median percent change ([IQR], n) from baseline in SCORAD was −67.1 ([−79.2; −54.2], n = 16), −70.5 ([−85.8; −47.9], n = 36) and −66.7 ([−77.3; −51.0], n = 13); and POEM, −58.6 ([−66.4; −55.5], n = 4), −73.0 ([−86.5; −66.7], n = 16) and −87.3 ([−93.4; −69.6], n = 8), respectively. Before initiation of dupilumab treatment, 82 (88.2%) patients reported at least 1 flare of AD in the past 12 months. During the follow-up period, 30 (32.3%) patients reported at least 1 exacerbation or flare. Twelve patients (12.9%) presented an AE and 3 (3.2%) patients discontinued dupilumab for this cause. Conclusions: Dupilumab was effective and safe for the treatment of moderate to severe AD in point-of-care settings, with results similar to randomized controlled and other real-life studies. These positive results are still maintained even though a high number of patients had short interruptions in the use of dupilumab due to administrative problems.

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods: Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from “strongly agree” to “strongly disagree”. Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as “strongly agree” to “agree” after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

Blue Rubber Bleb Nevus Syndrome, is a rare condition characterized by skin lesions caused by vascular malformations most frequently associated with lesions of the gastrointestinal tract, although rare, it can present with lesions in the central nervous system, thyroid, liver, spleen and lungs; common symptoms are: digestive tract bleeding and iron deficiency anemia. The main manifestation are skin lesions that are characterized by being button-like, with a bluish tint, covered by skin, called blue nevus with a rubbery consistency due to its rubber-like consistency. We present a case of Blue Rubber Bleb Nevus Syndrome with involvement in the central nervous and gastrointestinal systems.

Food allergy affects approximately 2–4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.

Summary:. DIEP flap is considered the gold standard technique for breast reconstruction. One of the most frequent contour deformities after breast reconstruction with DIEP flap is a step-off deformity at the interface between the native chest wall and the reconstructed breast. Different techniques have been used to address this problem. We describe the pyramidal flap as a simple, single stage and low risk procedure, which specifically corrects the step-off or tapering deformity of the reconstructed breast with DIEP flap.

Objectives: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). Methods: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA

Background: The United Nations Sustainable Development Goal for health (SDG3) poses complex challenges for signatory countries that will require clear roadmaps to set priorities over the next 15 years. Building upon the work of the Commission on Investing in Health and published estimates of feasible global mortality SDG3 targets, we analysed Mexico's mortality to assess the feasibility of reducing premature (0–69 years) mortality and propose a path to meet SDG3. Methods: We developed a baseline scenario applying 2010 age-specific and cause-specific mortality rates from the Mexican National Institute of Statistics and Geography (INEGI) to the 2030 UN Population Division (UNPD) population projections. In a second scenario, INEGI age-specific and cause-specific trends in death rates from 2000 to 2014 were projected to 2030 and adjusted to match the UNPD 2030 mortality projections. A third scenario assumed a 40% reduction in premature deaths across all ages and causes. By comparing these scenarios we quantified shortfalls in mortality reductions by age group and cause, and forecasted life expectancy pathways for Mexico to converge to better performing countries. Findings: UNPD-projected death rates yield a 25·9% reduction of premature mortality for Mexico. Accelerated reductions in adult mortality are necessary to reach a 40% reduction by 2030. Mortality declines aggregated across all age groups mask uneven gains across health disorders. Injuries, particularly road traffic accidents and homicides, are the main health challenge for young adults (aged 20–49 years) whereas unabated diabetes mortality is the single most important health concern for older adults (aged 50–69 years). Interpretation: Urgent action is now required to control non-communicable diseases and reduce fatal injuries in Mexico, making a 40% reduction in premature mortality by 2030 feasible and putting Mexico back on a track of substantial life expectancy convergence with better performing countries. Our study provides a roadmap for setting national health priorities. Further analysis of the equity implications of following the suggested pathway remains a subject of future research. Funding: Mexico's Ministry of Health, University of California, San Francisco, and Bill & Melinda Gates Foundation.

Aims: To study the AIDS welfare homes (AWHs) in Andalusia, assess their resources and the services provided, and describe the characteristics of their residents. Patients and Methods: Cross-sectional, observational study; an interview questionnaire technique was used with the managers and the residents of the AWHs. Results: A total of 7 AWHs and 96 residents were included; 32% of the staff were health care workers and 45.5% volunteers. The occupancy rate was 86% (2007) and 96% (2008). Residents’ characteristics: mean age 45.6 years, 73% male, 92% with at least 1 AIDS-defining disease, median Karnofsky index 60 (50-80), and median Barthel index 80 (40-100). Half the residents had physical sequelae and 31% mental sequelae. Conclusion: The AWHs perform an important role in the care of certain types of patients with HIV infection. They require human and material resources to be able to tackle the immense difficulties associated with this group of patients.

Background: Electromagnetic navigation bronchoscopy (ENB) has been developed as a novel ancillary tool for the bronchoscopic diagnosis of pulmonary nodules. Despite successful navigation in 90% of patients, ENB diagnostic yield does not generally exceed 70%. We sought to determine whether the presence of a bronchus sign on CT imaging conditions diagnostic yield of ENB and might account for the discrepancy between successful navigation and diagnostic yield.Methods: We conducted a prospective, single-center study of ENB in 51 consecutive patients with pulmonary nodules. ENB was chosen as the least invasive diagnostic technique in patients with a high surgical risk, suspected metastatic disease, or advanced-stage disease, or in those who demanded a preoperative diagnosis prior to undergoing curative resection. We studied patient and technical variables that might condition diagnostic yield, including size, cause, location, distance to the pleural surface, and fluorodeoxyglucose uptake of a given nodule; the presence of a bronchus sign on CT imaging; registration point divergence; and the minimum distance from the tip of the locatable guide to the nodule measured during the procedure.Results: The diagnostic yield of ENB was 67% (34/51). The sensitivity and specificity of ENB for malignancy in this study were 71% and 100%, respectively. ENB was diagnostic in 79% (30/38) patients with a bronchus sign on CT imaging but only in 4/13 (31%) with no discernible bronchus sign. Univariate analysis identified the bronchus sign (P = .005) and nodule size (P = .04) as statistically significant variables conditioning yield, but on multivariate analysis, only the bronchus sign remained significant (OR, 7.6; 95% CI, 1.8-31.7). No procedure-related complications were observed.Conclusions: ENB diagnostic yield is highly dependent on the presence of a bronchus sign on CT imaging. [ABSTRACT FROM AUTHOR]

Rationale: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. Objective: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. Results: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. Conclusion: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions. [ABSTRACT FROM AUTHOR]

Objective: Immunocytochemistry (ICC) is essential for enhancing diagnostic accuracy and identifying markers for diagnosis, prognosis and targeted therapies. While cell blocks (CBs) are preferred for standardization and optimized staining, cytological smears are an alternative when CBs are unavailable. However, the literature on ICC protocols for smears is sparse. This review addresses preparation, fixation and protocols for nuclear and cytoplasmic antibodies on smears, drawing from our laboratory's experience., Methods: We reviewed procedures for ICC on cytological smears using existing literature and practical insights from our laboratory., Results: Commercially available antibodies were found to be reliable for ICC on smears if specimens are properly prepared and fixed. Protocols developed in our laboratory maintained antigenicity and provided clear staining results., Conclusions: Although ICC on CBs is the gold standard for standardization, cytological smears are a viable alternative when CBs are unavailable. Success in ICC on smears depends on proper preparation and fixation. This review offers practical protocols and insights to help laboratories optimize ICC on cytological smears. Further research and standardization are necessary to enhance reproducibility and reliability of ICC on smears. The practical information provided is based on personal experience in our laboratory., (© 2024 The Author(s). Cytopathology published by John Wiley & Sons Ltd.)

Objective: The generally good prognosis of low- and intermediate-risk differentiated thyroid cancer (DTC) underscored the need to identify those few patients who relapse., Design: Records of 299 low- or intermediate-risk DTC patients (mean follow-up 8.2 ± 6.2 years) were retrospectively reviewed. The sample was classified following the American Thyroid Association (ATA) dynamic risk stratification (DRS) system., Patients and Measurement: After classifying patients according to DRS at the first visit following initial therapy (FU1), structural recurrence occurred in 2/181 (1.1%), 5/81 (6.2%) and 13/26 (50.0%) with excellent, indeterminate and biochemical incomplete response to treatment, respectively. All relapses but one happened within 5 years from FU1. Univariate analysis comparing excellent, indeterminate and biochemical incomplete with structural incomplete responses at the end of the follow-up, identified tumour size (p < .001), T status (<0.001), positive lymph nodes (N) (p < .01), multifocality (p < .004), need of additional radioactive iodine (RAI) (p < .0001) and first DRS status (p < .0003) as risk factors of recurrence. In the multivariate analysis, only RAI remained statistically significant (p < .02). Comparison between excellent and indeterminate with biochemical and structural incomplete responses, identified tumour size (p < .0004), T (p < .01), N (p < .0001), bilaterality (p < .03), first DRS status (p < .0001) and RAI (p < .001) as recurrence risk factors. T (p < .01) and first DRS (p < .0006) were confirmed in the multivariate analysis., Conclusions: Patients with DTC classified as low- or intermediate-risk of recurrence with excellent response to treatment at FU1 rarely develop structural disease and this occurs almost exclusively in the first 5 years. Initial DRS status is an accurate tool for determining the risk of recurrence., (© 2024 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background: Cytological samples play a critical role in diagnosing advanced-stage tumors and those arising in difficult-to-reach anatomical sites such as the pancreatobiliary tract, lung, thyroid, suprarenal, pelvis, and others such as salivary glands. These samples are often the only available material for accurate diagnosis and for performing ancillary studies, such as immunocytochemistry (ICC) or the detection of molecular biomarkers., Summary: While the use of immunohistochemistry is well established and standardized on formalin-fixed-paraffin-embedded histological tissue, in cytological samples, it presents unique challenges. Methods used for obtaining and processing these specimens are complex and are not standardized among laboratories. Moreover, there is also diversity in the types of cytological samples potentially suitable for ICC., Key Messages: This review explores the current landscape of ICC practices in European and North American laboratories, highlighting variability in methods and the need for standardization to ensure reliable results and reproducibility of ICC on cytological specimens., (© 2024 S. Karger AG, Basel.)

In the 21st century, there has been a dramatic shift in the diagnosis and management of non-small cell lung carcinoma (NSCLC), with an increasing use of minimally invasive tissue acquisition methods. Current treatments require morphologic subtyping and biomarker information in all cases. Determining such biomarkers is a continuously evolving field; current guidelines state that the determination of mutations on the Epidermal Growth Factor (EFGR), Kirsten Rat Sarcoma viral oncogene homolog (KRAS), Proto-oncogene B-Raf (BRAF), Human epidermal growth factor receptor 2 (HER2) and Anaplastic Lymphoma Kinase (ALK), genes as well as fusions on genes such as ROS Proto-Oncogene 1, Receptor Tyrosine Kinase (ROS1), MET proto-oncogene, receptor tyrosine kinase (MET), RET proto-oncogene (RET), and the Neurotrophic Tyrosine Receptor Kinase (NTRK) family is mandatory. While analyzing such alterations, some of them were first reported to be mutually exclusive, although in recent years, it has been shown otherwise in some of these cases. Moreover, so was the case with the concomitant expression of NTRK fusions and EGFR mutations. We present a case report of a patient with concomitant EGFR mutation and NTRK1 fusion., (© 2024 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

The recently published WHO Reporting System for Pancreaticobiliary Cytopathology (World Health Organization [WHO] System) is an international approach to the standardized reporting of pancreaticobiliary cytopathology, updating the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System). Significant changes were made to the categorization of benign neoplasms, intraductal neoplasms, mucinous cystic neoplasms, and malignant neoplasms considered low grade. Benign neoplasms, such as serous cystadenoma, categorized as Neoplastic: benign in the PSC system, are categorized as Benign/negative for malignancy in the WHO system. Pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, and gastrointestinal stromal tumor, categorized as Neoplastic: other in the PSC system, are categorized as Malignant in the WHO System in accord with their classification in the 5th edition WHO Classification of Digestive System Tumours (2019). The two new categories of Pancreaticobiliary Neoplasm Low-risk/grade and Pancreaticobiliary Neoplasm High-risk/grade are mostly limited to intraductal neoplasms and mucinous cystic neoplasms. Low-risk/grade lesions are mucinous cysts, with or without low-grade epithelial atypia. High-risk/grade lesions contain neoplastic epithelium with high-grade epithelial atypia. Correlation with clinical, imaging, and ancillary studies remains a key tenet. The sections for each entity are written to highlight key cytopathological features and cytopathological differential diagnoses with the pathologist working in low resource setting in mind. Each section also includes the most pertinent ancillary studies useful for the differential diagnosis. Sample reports are provided for each category. Finally, the book provides a separate section with risk of malignancy and management recommendations for each category to facilitate decision-making for clinicians., (© 2024 American Cancer Society.)

Introduction: The tissue immune microenvironment is associated with key aspects of tumor biology. The interaction between the immune system and cancer cells has predictive and prognostic potential across different tumor types. Spatially resolved tissue-based technologies allowed researchers to simultaneously quantify different immune populations in tumor samples. However, bare quantification fails to harness the spatial nature of tissue-based technologies. Tumor-immune interactions are associated with specific spatial patterns that can be measured. In recent years, several computational tools have been developed to increase our understanding of these spatial patterns., Topics Covered: In this review, we cover standard techniques as well as new advances in the field of spatial analysis of the immune microenvironment. We focused on marker quantification, spatial intratumor heterogeneity analysis, cell‒cell spatial interaction studies and neighborhood analyses., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: There is beauty in cytopathology. That beauty and art can be transmitted and shared through fun images on social media., Methods: As social media becomes more popular, pathologists and related professionals have started to share the images that they capture at work on their profiles, tagging them with the hashtag #Pathart. #Pathart hashtag unites two concepts innately related: Pathology and art., Results: When groups of pathologists share concurring ideas, the result is an explosion of creativity that spreads even to new professionals and students. In addition, it attracts the attention of people, dedicated to other subjects such as journalism, who, with their interactions, give visibility to our field. This helps counteract the stereotypes and gives people a better understanding of what we do and why it is important. Therefore, the more pathologists and related professionals meet and interact with each other, the better., Conclusions: #Pathart images raise great interest among professionals, which contributes to the creation of a united and strong community of pathologists some of whom are dedicated to cytology. Interaction and professional collaboration between these professionals can positively contribute to disseminating scientific content and creating work/research groups. This might have an impact, both direct and indirect, on improving the quality of diagnoses and treatments in our patients., (© 2024 John Wiley & Sons Ltd.)

Immunotherapy has become a promising cancer treatment in the past decade, and IHC is the most commonly used testing method for PDL-1/PD1 evaluation. In general, PD-L1 assays can be performed on both FFPE specimens and cytological samples. However, their use on smears is not yet well-established or validated. Nowadays, digital images and advanced algorithms can aid in interpreting PD-L1 in cytological samples. Understanding the immune environment of non-small cell lung cancer (NSCLC) is critical in developing successful anticancer immunotherapies. The use of a multiplexed immunofluorescence (mIF) assay on cytological samples obtained through minimally invasive methods appears to be a viable option for investigating the immune environment of NSCLC. This review aims to briefly summarize the knowledge of the role of cytopathology in the analysis of PD-L1 by immunocytochemistry (ICC) and future directions of cytopathology in the immunotherapy setting., (© 2023 The Authors. Cytopathology published by John Wiley & Sons Ltd.)

Introduction: The Global Initiative for Obstructive Lung Disease (GOLD) recommends lung cancer screening for patients with Chronic Obstructive Pulmonary Disease (COPD), but data is lacking regarding results of screening in this high-risk population. The main goal of the present work is to explore if lung cancer screening with Low Dose Chest Tomography (LDCT) in people with COPD, allows lung cancer (LC) diagnosis in early stages with survival compatible with curative state., Methods: This is a post hoc exploratory analysis. Pamplona International Early Lung Cancer Action Program (P-IELCAP) participants with a GOLD defined obstructive pattern (post bronchodilator FEV 1 /FVC<0.70) were selected for analysis. The characteristics of those who developed LC and their survival are described. A Cox proportional analysis explored the factors associated with LC diagnosis., Results: Eight hundred and sixty-five patients (77% male, 93% in spirometric GOLD stage 1+2) were followed for 102±63 months. LC prevalence was 2.6% at baseline, with an annual LC diagnosis rate of 0.68%. Early-stage tumors predominated (74%) with a median survival (25-75th percentiles) of 139 (76-185) months. Cumulative tobacco exposure, FEV 1 %, and emphysema were the main predictors of an LC diagnosis. Eight (11%) patients with COPD had a second LC, most of them in early stage (92%), and 6 (8%) had recurrence. Median survival (25-75th percentiles) in these patients was 168 (108-191) months., Conclusions: Lung cancer screening of selected high-risk participants with COPD allowed the LC diagnosis in early stages with survival compatible with curative state., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Biomarker tests in lung cancer have been traditionally ordered by the treating oncologist upon confirmation of an appropriate pathological diagnosis. The delay this introduces prolongs yet further what is already a complex, multi-stage, pre-treatment pathway and delays the start of first-line systemic treatment, which is crucially informed by the results of such analysis. Reflex testing, in which the responsibility for testing for an agreed range of biomarkers lies with the pathologist, has been shown to standardise and expedite the process. Twelve experts discussed the rationale and considerations for implementing reflex testing as standard clinical practice., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The World Health Organization (WHO), the International Academy of Cytology, and the International Agency for Research on Cancer have developed an approach to standardized reporting of pancreaticobiliary cytopathology. The WHO Reporting System for Pancreaticobiliary Cytopathology (WHO System) revises the Papanicolaou Society of Cytopathology (PSC) System for Reporting Pancreaticobiliary Cytology published in 2015 and replaces the 6 PSC categories with 7 categories: "Insufficient/Inadequate/Nondiagnostic"; "Benign/Negative for malignancy"; "Atypical"; "Pancreaticobiliary neoplasm, low risk/grade (PaN-low)"; "Pancreatic neoplasm, high risk/grade (PaN-High)"; "Suspicious for malignancy"; and "Malignant". In the PSC system, there is a single category for "Neoplastic" lesions that includes 2 groups, 1 for benign neoplasms and 1 named "Neoplastic-other", dominated by premalignant intraductal neoplasms primarily intraductal papillary mucinous neoplasms and low-grade malignant neoplasms (pancreatic neuroendocrine tumors (PanNET) and solid pseudopapillary neoplasms (SPN). In the WHO System, benign neoplasms with virtually no risk of malignancy are included in the "Benign" category and low-grade malignancies (PanNET and SPN) are included in the "Malignant" category, as per the 5th edition of the WHO Classification of Digestive System Tumors, while the non-invasive pre-malignant lesions of the ducts are divided by the cytomorphological grade of the epithelium into PaN-low and PaN-high with distinctly different risks of malignancy. Within each category, key diagnostic cytopathologic features and the ancillary studies for diagnostic and prognostic evaluation, as well as the implications of diagnosis for patient care and management, are outlined. Reporting and diagnostic management options recognize the variations in the availability of diagnostic and prognostic ancillary testing modalities in low- and middle-income countries., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: In many cancers, the expression of immunomodulatory ligands leads to immunoevasion, as exemplified by the interaction of PD-L1 with PD-1 on tumor-infiltrating lymphocytes. Profound advances in cancer treatments have come with the advent of immunotherapies directed at blocking these immuno-suppressive ligand-receptor interactions. However, although there has been success in the use of these immune checkpoint interventions, correct patient stratification for these therapies has been challenging., Materials and Methods: To address this issue of patient stratification, we have quantified the intercellular PD-1/PD-L1 interaction in formalin-fixed paraffin-embedded tumor samples from patients with non-small cell lung carcinoma, using a high-throughput automated quantitative imaging platform (quantitative functional proteomics [QF-Pro])., Results: The multisite blinded analysis across a cohort of 188 immune checkpoint inhibitor-treated patients demonstrated the intra- and intertumoral heterogeneity of PD-1/PD-L1 immune checkpoint engagement and notably showed no correlation between the extent of PD-1/PD-L1 interaction and PD-L1 expression. Importantly, PD-L1 expression scores used clinically to stratify patients correlated poorly with overall survival; by contrast, patients showing a high PD-1/PD-L1 interaction had significantly better responses to anti-PD-1/PD-L1 treatments, as evidenced by increased overall survival. This relationship was particularly strong in the setting of first-line treatments., Conclusion: The functional readout of PD-1/PD-L1 interaction as a predictive biomarker for the stratification of patients with non-small-cell lung carcinoma, combined with PD-L1 expression, should significantly improve the response rates to immunotherapy. This would both capture patients excluded from checkpoint immunotherapy (high PD-1/PD-L1 interaction but low PD-L1 expression, 24% of patients) and additionally avoid treating patients who despite their high PD-L1 expression do not respond and suffer from side effects.