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* Purpose.--To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification. Methods.--The Update Panel conducted a systematic literature review to identify signals for updating recommendations. Results.--The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations. Recommendations.--The 2018 ASCO-CAP recommendations for HER2 testing are affirmed. Discussion.--HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines., The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) first published a practice guideline on human epidermal growth factor receptor 2 (HER2) testing in breast [...]

Background: Studies have estimated that a large backlog of procedures was generated by emergency measures implemented in Ontario, Canada, at the onset of the COVID-19 pandemic, when nonessential and scheduled procedures were postponed. Understanding the impact of the COVID-19 pandemic on the time needed to perform a procedure may help to determine the resources needed to tackle the substantial backlog caused by the deferral of cases. The purpose of this study was to examine the duration of operating room (OR) procedures before and after the onset of the COVID-19 pandemic to inform planning around changes in required resources. Methods: A population-based, retrospective cohort study was conducted using Ontario Health Insurance Plan claims data and other administrative health care data from Apr. 1, 2019, to Sept. 30, 2020. Statistical analysis was conducted using multivariate regression, with procedure duration as the outcome variable. Results: Results showed that the average duration of nonelective procedures increased by 34 minutes during the COVID-19 period and by 19 minutes after the resumption of scheduled procedures. Controlling for physician, patient and hospital characteristics, and the procedure code submitted, procedure duration increased by 12 minutes in the nonelective COVID-19 period and by 5 minutes when scheduled procedures resumed, compared with the pre-COVID-19 period. Conclusion: Procedures may take longer in the COVID-19 period. This will affect wait times, which had already increased because of the deferral of procedures at the beginning of the pandemic, and will have an impact on Ontario's ability to provide patients with timely care. Contexte : Selon des etudes, on estime que la mise en place des mesures d'urgence en Ontario (Canada) au debut de la pandemie de COVID-19, qui ont entraine le report de toutes les interventions planifiees et non essentielles, a mene a l'accumulation d'un retard important des interventions chirurgicales. Comprendre l'incidence de la pandemie de COVID-19 sur le temps necessaire pour realiser une intervention pourrait aider a determiner les ressources requises pour s'attaquer a cet arriere considerable. Le but de cette etude etait d'observer la duree des interventions en salle d'operation avant et apres le debut de la pandemie de COVID-19 pour mieux planifer les changements aux ressources necessaires. Methodes : Une etude de cohorte retrospective populationnelle a ete menee a l'aide des donnees sur les reclamations medicales soumises au Regime d'assurance-sante de l'Ontario et d'autres donnees administratives sur les soins de sante du 1 (er) avril 2019 au 30 septembre 2020. L'analyse statistique a ete realisee au moyen d'une regression multivariable, ou la duree de l'intervention constituait la variable dependante. Resultats : Les resultats ont montre que la duree moyenne des interventions non urgentes a augmente de 34 minutes durant la periode de restrictions associees a la COVID-19, et de 19 minutes apres la reprise des interventions planifees. En tenant compte de variables comme les caracteristiques du medecin, du patient et de l'hopital ainsi que des codes d'acte soumis, le temps moyen des interventions a augmente de 12 minutes pendant la periode de restrictions associees a la COVID-19 pour les interventions non urgentes et de 5 minutes apres la reprise des interventions planifees comparativement a la periode precedant la COVID-19. Conclusion : Les interventions peuvent prendre plus de temps en contexte de COVID-19. Cela influencera les temps d'attente, qui ont deja augmente en raison du report des interventions au debut de la pandemie, et aura des repercussions sur la capacite de l'Ontario a fournir aux patients des soins dans des delais raisonnables., On Mar. 11, 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. (1) Since then, 90% of countries have reported an interruption in essential health services caused by [...]

When initial treatments for depression do not work, patients often feel responsible. They blame themselves, feel stigmatized, and think they are not trying hard enough. Family relationships and work suffer. [...]

Background: Burnout among resident physicians has been an area of concern that predates the COVID- 19 pandemic. With the significant turmoil during the pandemic, this study examined resident physicians' burnout, depression, anxiety, and stress as well as the benefits of engaging in activities related to wellness, mindfulness, or mental wellbeing. Methods: The authors conducted a cross-sectional survey of 298 residents from 13 residency programs sponsored by the University of Kansas School of Medicine-Wichita, in October and November 2021. Authors used a 31-item questionnaire to measure levels of burnout, depression, anxiety, and stress. A mixed method approach was used to collect, analyze, and interpret the data. Descriptive statistics, one- way ANOVA/Kruskal-Wallis tests, adjusted odds ratios (aOR), and immersion- crystallization methods were used to analyze the data. Results: There was a 52% response rate, with 65.8% (n=102) of the respondents reporting manifestations of burnout. Those who reported at least one manifestation of burnout experienced a higher level of emotional exhaustion (aOR=6.73; 95% CI, 2.66-16.99; P Conclusion: The findings suggest the COVID-19 pandemic is associated with a significant and worsening prevalence of burnout and other negative mental health effects on residents. Appropriate wellness and mental health support initiatives are needed to help resident physicians thrive in the health care environment., Presenters Samuel Ofei-Dodoo, PhD, MA, MPA, CPH, Kimberly Krohn, MD, FAAFP, MPH, Maurice Duggins, MD, Kimberly Williams, MD, Philip Dooley, MD, FAAFP, Gretchen Irwin, MD, MBA, Brynn Wright, [...]

Context.--There is interest in using transbronchial cryobiopsies (CBs) for the diagnosis of fibrotic (chronic) hypersensitivity pneumonitis (FHP), but with little information in the literature about what features are diagnostic in CBs. Objective.--To determine, using in silico investigation, whether features supporting a diagnosis of FHP in video-assisted thoracoscopic (VATS) biopsies can be identified in CBs. Design.--In silico circular 'cryobiopsies,' 5.25 mm in diameter (21.6 [mm.sup.2]), were created on the slides of 15 VATS biopsy cases that had been assigned a 60% or greater confident diagnosis of FHP at a specially devised multidisciplinary discussion. Using stratified random sampling, up to 8 'cryobiopsies' per case were analyzed for the presence of giant cells/granulomas or peribronchiolar metaplasia affecting 50% or more of the bronchioles, features that had statistically supported a diagnosis of FHP on the VATS biopsies in the multidisciplinary discussion exercise. Results.--Giant cells/granulomas were detected with very low sensitivities in the 'cryobiopsies.' Using peribronchiolar metaplasia in 50% or more of bronchioles alone, the sensitivity/specificity for a diagnosis of FHP of 2 'cryobiopsies' compared to the corresponding VATS biopsy was 0.57/0.63; for 4 'cryobiopsies,' 0.86/0.75; and for 8 'cryobiopsies,' 0.83/0.71. Adding giant cells/ granulomas slightly improved these numbers to 0.63/0.71 for 2 'cryobiopsies'; 1.00/0.86 for 4; and 1.00/0.80 for 8. Conclusions.--In the setting of a multidisciplinary discussion where FHP is part of the differential diagnostic choices, 4 actual CBs with an area of roughly 20 [mm.sup.2] each should have good sensitivity and reasonable specificity for diagnosing FHP using these specific morphologic criteria. doi: 10.5858/arpa.2020-0176-OA, The diagnosis of fibrotic hypersensitivity pneumonitis (also referred to as chronic hypersensitivity pneumonitis, hereafter called FHP) is frequently a difficult problem, because many of the clinical, radiologic, and pathologic features [...]

To the Editor.--Although many pulmonologists are adopting transbronchial cryobiopsy, there is a remarkable dearth of information on the specific pathologic features used to diagnose various forms of interstitial lung disease [...]

* Context.--Frederick Banting, Charles Best, J. Bertrand Collip, and J. J. R. Macleod contributed to the discovery of insulin in 1921-1922. Recent advances in anatomic pathology, experimental pathology, and clinical pathology were necessary for the research in Toronto, Ontario, Canada, to begin and to succeed. Objective.--To explore the role of pathology and laboratory medicine in laying the foundation for the discovery of insulin. Design.--Available primary and secondary historical sources were reviewed. Results.--During a 3-decade period, pathologists, through autopsy pathology and experimental animal studies, were able to provide solid evidence that the pancreatic islets were the source of the internal secretion responsible for proper carbohydrate metabolism. Banting, a surgeon with no previous research experience, read about these studies in a case report with an extensive literature review by pathologist Moses Barron; this piqued Banting's interest and caused him to approach Macleod, a Toronto physiology professor, with an idea that initiated the research. Advances in clinical laboratory medicine, which allowed them to measure blood glucose levels using small blood volumes, were critical to their success. Conclusions.--By 1921-1922, the pieces necessary to solve the puzzle were available. The primary reason that the time was ripe for the discovery was the contributions of pathologists and laboratory physicians in the preceding 3 decades. As the 100th anniversary approaches, our profession can take pride in its important contributions to the discovery of insulin, which is broadly recognized as one of the most important medical research advances of the 20th century. (Arch Pathol Lab Med. 2020;144:894-904; doi: 10.5858/arpa.2019-0400-HP), We are approaching the 100th anniversary of the discovery of insulin. Depending upon which historian you believe, insulin was discovered sometime between the summer of 1921, when Frederick Banting, MD [...]

By July 2023, family medicine residency programs will need to make major changes to their programs to meet new ACGME requirements. The 2023 requirements reflect the first major update for [...]

Background: Many cancer survivors live with postoperative complex abdominal wall hernias (CAWHs). However, the impact of CAWHs on their quality of life is unknown, and few descriptions of patient experiences exist. We performed a qualitative study to explore cancer survivors' experience with CAWHs before and after repair. Methods: Patients waiting to undergo CAWH repair or who had completed the surgery in the previous 18 months were identified from a single surgeon's practice in CAWH at a tertiary care centre. Clinical and demographic data were extracted from the electronic patient record. An in-depth semistructured interview guide was developed by experts in CAWH and qualitative methodology. Interviews were conducted in March 2013. We used comparative analysis techniques and coding strategies to identify themes. Results: Ten preoperative and 12 postoperative participants were interviewed. The average age of the participants was 64 years in both groups, with an even sex distribution. The most frequently diagnosed cancer in both groups was colorectal cancer. Participants' views were organized into 5 themes: 1) unable to return to normal life, 2) sense of abandonment, 3) experiencing fear and distress, 4) preoperative: desperate for help and 5) postoperative: 'getting my life back.' Conclusions: Our findings show the all-encompassing impact of a CAWH on the life of cancer survivors. They strongly suggest that hernia management should be viewed as an integral part in the continuum of cancer treatment to improve the quality of life of cancer survivors with hernias. Contexte : De nombreux survivants du cancer vivent avec des hernies postoperatoires complexes de la paroi abdominale (HCPA). Or, on ignore quel en est l'impact sur la qualite de vie, et peu de descriptions existent quant a l'experience des patients. Nous avons procede a une etude qualitative pour analyser l'experience des survivants du cancer presentant des HCPA, avant et apres une cure de hernie. Methodes : Les patients attendant une cure d'HCPA ou ayant subi une telle chirurgie dans les 18 mois precedents ont ete identifies a partir de la clientele d'un seul chirurgien pratiquant la cure d'HCPA dans un centre de soins tertiaires. Des donnees cliniques et demographiques ont ete extraites des dossiers electroniques des patients et un guide d'entrevue semi-structuree a ete concu par des experts de la cure d'HCPA et de methodologie qualitative. Les entrevues ont ete realisees en mars 2013. Nous avons utilise des techniques d'analyse comparative et des strategies de codage pour cerner les themes. Resultats : Dix participants ont ete interroges en periode preoperatoire et 12 en periode postoperatoire. L'age moyen etait de 64 ans dans les 2 groupes et il y avait autant d'hommes que de femmes. Le cancer le plus souvent diagnostique dans les 2 groupes etait le cancer colorectal. Les perceptions des participants ont ete organisees autour de 5 themes : 1) incapacite de retourner a la vie normale, 2) sentiment d'abandon, 3) sentiment de peur et de detresse, 4) preoperatoire : immense besoin d'aide et 5) post operatoire : <>. Conclusion : Nos observations font la lumiere sur l'impact global de l'HCPA sur la vie des survivants de cancer. Elles suggerent fortement que la cure de hernie devrait faire partie integrante du continuum therapeutique en oncologie pour ameliorer la qualite de vie des survivants du cancer porteurs de hernies., Patients with cancer are achieving improved longterm survival as a result of advances in early detection and multimodal, complex therapeutic regimens. (1) As of 2017, an estimated 60% of Canadians [...]

Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders (LSDs). Initial symptoms of cystinosis correspond to the renal Fanconi syndrome. Patients then develop chronic kidney disease and multi-organ failure due to accumulation of cystine in all tissue compartments. LSDs are commonly characterized by a defective activity of lysosomal enzymes. Hematopoietic stem and progenitor cell (HSPC) transplantation is a treatment option for several LSDs based on the premise that their progeny will integrate in the affected tissues and secrete the functional enzyme, which will be recaptured by the surrounding deficient cells and restore physiological activity. However, in the case of cystinosis, the defective protein is a transmembrane lysosomal protein, cystinosin. Thus, cystinosin cannot be secreted, and yet, we showed that HSPC transplantation can rescue disease phenotype in the mouse model of cystinosis. In this review, we are describing a different mechanism by which HSPC-derived cells provide cystinosin to diseased cells within tissues, and how HSPC transplantation could be an effective one-time treatment to treat cystinosis but also other LSDs associated with a lysosomal transmembrane protein dysfunction., Author(s): Celine J. Rocca [sup.1] , Stephanie Cherqui [sup.1] Author Affiliations: (Aff1) 0000 0001 2107 4242, grid.266100.3, Department of Pediatrics, Division of Genetics, University of California, , 9500 Gilman Drive, [...]

* Context.--Lesion localization during intraoperative frozen section of lung resection specimens can be challenging. Imaging could aid lesion localization while enabling 3dimensional specimen analysis. Objective.--To assess the feasibility of integrating micro-computed tomography (micro-CT) into the perioperative evaluation of fresh surgical lung resection specimens. Design.--Fresh lung specimens from patients with a presumptive diagnosis of lung cancer were imaged with micro-CT prior to routine histopathologic and molecular analysis. Micro-CT images were assessed to determine image quality, lesion size, and distance from lesion to the nearest surgical margin. Micro-CT measurements were compared to pathologic measurements using Bland-Altman analysis. Results.--A total of 22 specimens from 21 patients were analyzed (mean image acquisition time, 13 [+ or -] 6 minutes). Histologic quality of imaged specimens was indistinguishable from a control group of nonimaged lung specimens. Artifacts, most commonly from specimen deflation (n = 8), obscured fine detail on micro-CT images of 10 specimens. Micro-CT could successfully localize the target lesion in the other 12 specimens. Distance to the nearest surgical margin was determined in 10 specimens. Agreement of micro-CT with final pathology was good, with a mean difference of -2.8% (limits of agreement -14.5% to 20.0%) for lesion size and -0.5 mm (limits of agreement -4.4 to 3.4 mm) for distance to nearest surgical margin. Conclusions.--Micro-CT of fresh surgical lung specimens is feasible and has the potential to evaluate the size and location of lesions within resection specimens, as well as distance to the nearest surgical margin, all without compromising specimen integrity. doi: 10.5858/arpa.2018-0249-OA), Although lung cancer remains the leading cause of cancer-related mortality, (1) lesions detected at an early stage, prior to nodal or distant spread, are amenable to curative resection. Fundamental to [...]

* Context.--Specimen misidentification is the most significant error in laboratory medicine, potentially accounting for hundreds of millions of dollars in extra health care expenses and significant morbidity in patient populations in the United States alone. New technology allows the unequivocal documentation of specimen misidentification or contamination; however, the value of this technology currently depends on suspicion of the specimen integrity by a pathologist or other health care worker.Objective.--To test the hypothesis that there is a detectable incidence of unsuspected tissue specimen misidentification among cases submitted for routine surgical pathology examination.Design.--To test this hypothesis, we selected specimen pairs that were obtained at different times and/or different hospitals from the same patient, and compared their genotypes using standardized microsatellite markers used commonly for forensic human DNA comparison in order to identify unsuspected mismatches between the specimen pairs as a trial of 'molecular auditing.' We preferentially selected gastrointestinal, prostate, and skin biopsies because we estimated that these types of specimens had the greatest potential for misidentification.Results.--Of 972 specimen pairs, 1 showed an unexpected discordant genotype profile, indicating that 1 of the 2 specimens was misidentified. To date, we are unable to identify the etiology of the discordance.Conclusions.--These results demonstrate that, indeed, there is a low level of unsuspected tissue specimen misidentification, even in an environment with careful adherence to stringent quality assurance practices. This study demonstrates that molecular auditing of random, routine biopsy specimens can identify occult misidentified specimens, and may function as a useful quality indicator.(Arch Pathol Lab Med. 2018;142:1407-1414; doi: 10.5858/arpa.2017-0374-OA), ERRORS IN THE DIAGNOSTIC LABORATORYOne of the most important interfaces between patients and the health care system is the medical laboratory. Medical laboratory testing provides information to help maintain the [...]

Background: General surgeons' retirement plans have wide-ranging personal, professional and system-level effects. We explored the drivers of and barriers to surgeon retirement to identify opportunities to support career-long retirement planning. Methods: We conducted a qualitative study from May to October 2016 using semi-structured telephone interviews (mean duration 29 min) with general surgeons in Ontario. We used a purposive sampling strategy to recruit surgeons at 3 career stages (no plans to retire within next 5 yr, had slowed down practice or planned to slow down within 5 yr, and no longer operating as primary surgeon). We analyzed the data using established techniques of thematic analysis. Results: We interviewed 22 general surgeons. Their retirement status ranged from fully retired to no plans to retire. Preservation of reputation and quality care, commitment and succession planning, and retirement planning were dominant themes. Mid-career and senior surgeons' plans were made later in their careers and were driven by desires to preserve reputations and surgical identity. Younger surgeons' ([less than or equal to] 50 yr) early retirement was driven by lifestyle choices and work environment. Logistical barriers and financial insecurity led to retirement delay. Conclusion: Surgeons begin to plan for retirement both early and late in their careers. Most surgeons wish to establish retirement plans that allow for the gradual reduction of surgical patient care and the creation of job opportunities for younger colleagues balanced by a continued contribution to the profession. Opportunities to support surgeons at all career stages in their retirement planning require further exploration. Contexte : Les plans de retraite des chirurgiens generaux ont de vastes repercussions, tant a l'echelle personnelle et professionnelle qu'a l'echelle des systemes de sante. Nous avons analyse les facteurs qui favorisent ou retardent le depart a la retraite des chirurgiens afin de degager les elements qui pourraient favoriser une planification de la retraite echelonnee tout au long de la carriere. Methodes : Nous avons procede a une etude qualitative entre mai et octobre 2016 a l'aide d'entrevues telephoniques structurees (duree moyenne 29 minutes) aupres de chirurgiens generaux de l'Ontario. Nous avons utilise une strategie d'echantillonnage par choix raisonne pour recruter des chirurgiens a 3 stades de carriere (ne prevoyant pas prendre leur retraite d'ici 5 ans, ayant ralenti leur pratique ou prevoyant la ralentir d'ici 5 ans, et ayant cesse d'occuper un poste de chirurgien principal). Nous avons analyse les donnees a l'aide de techniques d'analyses thematiques reconnues. Resultats : Nous avons interroge 22 chirurgiens generaux dont la situation par rapport a la retraite allait de la retraite complete a l'absence de plan de retraite. Les themes principaux etaient le maintien de la reputation et de la qualite de soins, l'engagement et planification successorale et la planification de la retraite. Les plans des chirurgiens en milieu de carriere et << seniors >> se faisaient plus tard durant leur parcours professionnel et etaient motives par le souhait de preserver leur reputation et leur identite en tant que chirurgiens. Le depart hatif a la retraite des chirurgiens plus jeunes (< 50 ans) etait motive par des choix de style de vie et par l'environnement de travail. Des obstacles logistiques et l'insecurite financiere ont pu retarder certains departs a la retraite. Conclusion : Les chirurgiens commencent a planifier leur retraite tot et tard en cours de carriere. La plupart des chirurgiens souhaitent planifier leur retraite de maniere a pouvoir reduire graduellement leur charge de travail aupres des patients et creer des possibilites d'emploi pour leurs jeunes collegues, tout en maintenant un apport equilibre et continu a la profession. Les mesures visant a soutenir les chirurgiens dans la planification de leur retraite a tous les stades de leur carriere devront faire l'objet d'etudes plus approfondies., Retirement from surgery is both a deeply personal and a public matter. Surgeons' decisions about retirement and late-career transition are important for their sense of personal and professional identity, and [...]

* Research done in 455 individuals with osteoarthritis * Niacinamide eliminated or significantly reduced osteoarthritis pain in the large majority of individuals * Niacinamide can prevent joint replacement surgery *Why [...]