Before the Civil War, there was little scientific research and no federally funded scientific research in America. William Hammond, a US Army surgeon, organized a small group of young Philadelphia-based physicians and established the Philadelphia Biological Society while on sick leave in December 1857. It was a short-lived society that promoted self-funded biomedical research. Hammond, after his appointment as Surgeon-General during the Civil War, realized that by utilizing his new top-down authority and military funding, he could conduct scientific research and envisioned producing an all-inclusive Medical and Surgical History of the War of the Rebellion. On May 21, 1862, Hammond ordered Union Army doctors to diligently collect and forward to him "all specimens of morbid anatomy, surgical or medical, which may be regarded as valuable … in the study of military medicine or surgery." The Army Medical Museum was established on August 1, 1862, to receive these materials. In addition to the officers in charge, the Museum required a small technical staff with highly specialized skills. A German immigrant anatomy technician who had been working at the University of Pennsylvania, Frederick Schafhirt, was hired as a "bone cleaner" on July 24, 1862. Soon, his sons Adolph and Ernest were working with him. Of the little that has been written about these colorful individuals, much is historically incorrect. This paper documents their lives and work at the Museum. Frederick Schafhirt was almost certainly the first federally funded research employee, and the Army Medical Museum represents the beginning of federally funded research in America.

Context.—:Although pathology at McGill's teaching hospitals famously began with William Osler, he left Montreal before the medical school had established a pathology department. Objective.—:To explore the early history of academic pathology and its leadership at McGill, with a primary focus on the second department head, Horst Oertel. Design.—:Available primary and secondary historical resources were reviewed. Results.—:John George Adami, the first professor of pathology, recruited Oertel in 1914, and Oertel became acting department head when Adami enlisted. At the end of World War I, Adami did not return, and Oertel was appointed department head. In the early 1920s, using Rockefeller Foundation and other philanthropic funding, Oertel oversaw the establishment of a new McGill Pathological Institute; unfortunately, he based the institute upon an autopsy-centric 19th-century German model, even though surgical pathology and clinical pathology were beginning to blossom elsewhere in North America. As a result, McGill missed an opportunity to lead in these arenas. This paper dissects Oertel's fascinating but tumultuous professional career at McGill, including his battles with renowned neurosurgeon/neuropathologist Wilder Penfield, medical museum/congenital heart disease specialist Maude Abbott, and McGill's Dean of Medicine Charles Martin, who expected the newly created institute to raise the faculty's research profile by promoting collaborative clinical research. Oertel was a legendary educator who wove history, philosophy, and humanities into his pathology lectures. Conclusions.—:Oertel's legacy at McGill was mixed. Although he was considered strong academically, more forward-looking and collaborative leadership could have positioned McGill near the forefront of North American pathology.

CONTEXT.—:The year 2023 marks the centenary of the Nobel Prize honoring the discovery of insulin. Little-known experimental pathologists Lydia DeWitt, MD, at the University of Michigan and Mary Kirkbride, DSc [Hon], at Columbia University, both just beginning their academic careers, made independent contributions to the discovery that have never been critically examined. This happened at a time when it was exceedingly rare for women to work in pathology. OBJECTIVE.—:To explore the facilitative roles of DeWitt and Kirkbride in the discovery of insulin and to examine their trail-breaking careers in academic pathology. DESIGN.—:Available primary and secondary historical resources were reviewed. RESULTS.—:DeWitt made and tested pancreatic extracts from duct-ligated atrophic pancreas (ie, Frederick Banting's great idea to prevent digestion of its hypothetical internal secretion) 15 years before Banting; Banting was unaware of her work. His idea came from reading a paper by pathologist Moses Barron. Prior duct-ligation studies had sometimes been viewed with skepticism because histologic identification of islets in atrophic duct-ligated pancreata was imperfect; Kirkbride addressed this with histochemical staining, convincing Barron and, therefore, indirectly influencing and motivating Banting. The lives and convoluted careers of these 2 early-20th-century women are explored and compared with those of other contemporary women in pathology. A unifying pattern becomes clear: careers in experimental pathology and bacteriology were accepted but performing clinical work in anatomic pathology was not. CONCLUSIONS.—:Both DeWitt and Kirkbride are prototypical early-20th-century women in academic pathology whose careers were constrained by gender. However, Kirkbride made a unique and unrecognized contribution to the discovery of insulin.

Maude Abbott was a pioneering female Canadian physician who became a world authority on medical museums and congenital heart disease. Abbott spent almost all her career in highly sexist, discriminatory work environments. This paper reviews Abbott’s life and accomplishments, but, more importantly, analyzes her pathway to success in the masculine world of early 20th-century academic pathology. Abbott, though well-trained as a pathologist, never provided clinical service, but instead worked as museum curator at McGill University. She established the International Association of Medical Museums (predecessor to the International Academy of Pathology), edited its journal, and essentially ran the organization. Abbott, surrounded by influential males, dealt differently with each. In general, she recognized that male doctors believed women lacked the gravitas to lead major initiatives but that she could circumnavigate this supposed impediment by co-leading projects with male counterparts, preferably ones too busy to get in her way. She repeatedly used this approach, and by doing most of the work but sharing credit, succeeded in gaining reputation, accomplishment, and advancement. Abbott’s pioneering work on congenital heart disease established her as one of the founders of pediatric pathology, and, overall, her career promoted the entry of women physicians into the pathology profession.

Maud Menten was born and raised in remote regions of Canada. She obtained her MB/MD at the University of Toronto (1907/1911) and her PhD in biochemistry at the University of Chicago (1916). From 1907 to 1916, she trained at the Rockefeller Institute for Medical Research, the New York Infirmary for Women and Children, Western Reserve University in Cleveland, the Berlin Municipal Hospital in Germany, and the Barnard Free Skin and Cancer Hospital in St Louis. In 1916, she was appointed as pathologist at the Elizabeth Steel Magee Hospital, a charitable maternity hospital in Pittsburgh. She received a faculty appointment at the University of Pittsburgh (1918) and was appointed pathologist at Pittsburgh Children's Hospital (1926). In addition to being one of the first woman academic pathologists, she was likely the first perinatal, the second pediatric-perinatal, and the fourth pediatric pathologist to practice in North America. The importance of Menten's overall scientific contributions place her in the very upper echelon of 20th century pathologists. Her enzyme kinetic work resulted in the Michaelis-Menten equation, and her work in George Crile's laboratory in Cleveland provided a physiological basis for improved surgical outcomes. Her work in Pittsburgh was equally innovative, including initiating the field of enzyme histochemistry.

Context.— In the late 19th century, mutual autopsy societies formed, first in Paris, France (1876) and later in Philadelphia, Pennsylvania. Members, who were often a who's who of anthropologists, physicians, intellectuals, and highly accomplished citizens, pledged to submit their bodies for autopsies to be performed by living society members so that their brains could be weighed and surface topography studied, with the results to be correlated with the decedents' intelligence and personal strengths during life. Objective.— To explore the short history of these societies, the science they produced, and their extensive newspaper coverage in the United States. Design.— Available primary and secondary historic sources were reviewed. Results.— The Société Mutuelle d'Autopsie in Paris and the American Anthropometric Society in Philadelphia had different motives, as the former was heavily influenced by French Third Republic politics and secularism. The American press provided titillating coverage of both and was particularly fascinated by scandals. In America, Burt Wilder formed a splinter group and established the Wilder Brain Collection at Cornell University. In a period where many anthropologists were making untrue claims that brain and skull measurements were largely determined by race and sex, Wilder and Franklin P. Mall of the Wistar Institute in Philadelphia independently published carefully conducted studies proving this was not the case. Conclusions.— Mutual autopsy societies and brain clubs conclusively established that brain weight was not an accurate predictor of intelligence but accomplished little else; they were phased out shortly after World War I but are the predecessor to modern-day brain banks.

After the discovery of insulin at the University of Toronto in 1921-22, Frederick Banting and Charles Best downplayed the contributions of physiology professor John James Rickard Macleod, the director of the laboratory where the discovery was made. Banting and Best, their allies, and to a lesser extent the university promoted a "fairy tale" version in which the two young investigators made the discovery on their own, creating the so-called "Banting and Best myth." Over the next 60 years, the myth prevailed and Macleod's reputation became increasingly tarnished, with both Banting and Best actively maligning their former mentor. While the publication of Michael Bliss' The Discovery of Insulin in 1982 placed Macleod's reputation on the road to recovery, there are still many lingering issues that have been raised, and Macleod remains misunderstood, misinterpreted, and maligned. This paper, using primary and secondary historical sources, addresses topics that have been repetitively raised by Macleod's detractors over the past century. Apres la decouverte de l'insuline a l'Universite de Toronto en 1921-1922, Frederick Banting et Charles Best ont minimise les contributions du professeur de physiologie John James Rickard Macleod, directeur du laboratoire ou la decouverte a ete faite. En compagnie de leurs allies et dans une certaine mesure de l'Universite, Banting et Best ont propage un conte de fee dans lequel les deux jeunes chercheurs auraient fait cette decouverte par eux-memes, donnant ainsi naissance au & DLANGBRAC; mythe Banting et Best & drangbrac;. Au cours des 60 annees suivantes, ce mythe a prevalu et la reputation de Macleod a ete ternie, Banting et Best s'employant a calomnier leur ancien mentor. Si la publication de The Discovery of Insulin (1982) par Michael Bliss a quelque peu retabli la reputation de Macleod, celui-ci est encore largement incompris, mal interprete et denigre. En s'appuyant sur des sources historiques premieres et secondaires, cet article aborde les enjeux qui ont ete souleves de maniere repetee par les detracteurs de Macleod au cours du XXe siecle.

Living in variable and unpredictable environments, organisms face recurrent stressful situations. The endocrine stress response, which includes the secretion of glucocorticoids, helps organisms to cope with these perturbations. Although short-term elevations of glucocorticoid levels are often associated with immediate beneficial consequences for individuals, long-term glucocorticoid elevation can compromise key physiological functions such as immunity. While laboratory works highlighted the immunosuppressive effect of long-term elevated glucocorticoids, it remains largely unknown, especially in wild animals, whether this relationship is modulated by individual and environmental characteristics. In this study, we explored the co-variation between integrated cortisol levels, assessed non-invasively using faecal cortisol metabolites (FCMs), and 12 constitutive indices of innate, inflammatory, and adaptive immune functions, in wild roe deer living in three populations with previously known contrasting environmental conditions. Using longitudinal data on 564 individuals, we further investigated whether age and spatio-temporal variations in the quantity and quality of food resources modulate the relationship between FCMs and immunity. Negative covariation with glucocorticoids was evident only for innate and inflammatory markers of immunity, while adaptive immunity appeared to be positively or not linked to glucocorticoids. In addition, the negative covariations were generally stronger in individuals facing harsh environmental constraints and in old individuals. Therefore, our results highlight the importance of measuring multiple immune markers of immunity in individuals from contrasted environments to unravel the complex relationships between glucocorticoids and immunity in wild animals. Our results also help explain conflicting results found in the literature and could improve our understanding of the link between elevated glucocorticoid levels and disease spread, and its consequences on population dynamics.

Introduction: Eosinophilic/T-cell chorionic vasculitis (E/TCV), an incidental finding primarily in third trimester placentas, is characterized by eosinophils and CD3+ T lymphocytes infiltrating at least 1 chorionic and/or stem villous vessels. Its etiology and clinical significance are unclear. Methods: Placental pathology reports issued by 8 pediatric-perinatal pathologists at Alberta Children’s Hospital were retrieved from the lab information system (2010–2022), and candidate reports were identified using a Perl script searching for “eosinophil.” Candidate diagnoses of E/TCV were validated by pathologist review. Results: 38,058 placenta reports from 34,643 patients were reviewed; 328 cases of E/TCV were identified, for an overall incidence of 0.86%. Incidence increased 23% per year, from 0.11% in 2010 to 1.5% in 2021 ( P < .01). This temporal change was observed for all pathologists; the incidence of identified multifocality also increased over time ( P < .01). Umbilical vascular involvement was exceedingly rare. No variation in incidence was attributable to season. We received more than 1 placenta from 46 mothers with an E/TCV placental diagnosis; examination of >1 placenta did not reveal any mother with >1 E/TCV diagnosis. Conclusions: The incidence of E/TCV increased steadily over a ~12-year period and no recurrent cases were observed.

Background: Noncompaction of ventricular myocardium is a cardiomyopathy that typically involves the left ventricle or both ventricles; it has often been associated with mutations in genes encoding sarcomere proteins. Little is known about isolated right ventricular noncompaction, as only a few cases have been reported. Case Report: A 30 year old G2P1 woman experienced a spontaneous fetal loss at 19 weeks and 4 days. An ultrasound examination at 19 weeks showed right ventricular and tricuspid valve abnormalities, ascites, and early hydrops. At autopsy, the right ventricular chamber was dilated with numerous prominent trabeculations and deep intrabecular recesses as well as a dysplastic tricuspid valve. Histologic examination confirmed isolated right ventricular noncompaction. Whole exome sequencing showed a likely pathogenic variant in the MYH7 gene. Conclusions: This appears to be the first report of isolated right ventricular noncompaction associated with a gene mutation as well as the first diagnosis in a fetus.

Dick van Velzen practiced as a pediatric pathologist at Alder Hey Children's Hospital in Liverpool, England from September 1988 until December 1995; he then relocated to the IWK-Grace Health Centre, a children's and maternity hospital in Halifax, Nova Scotia, Canada, where he practiced until he was fired for cause in January 1998. About a year and a half later, his practice in Liverpool came under increasing scrutiny, with the initial focus on the massive collection of post-mortem pediatric organs he had accumulated for planned future research on sudden infant death syndrome. Soon, a Parliamentary Inquiry began investigating the full scope of his Liverpool practice. During the Inquiry, another organ-hoarding scandal erupted; van Velzen, when leaving Halifax after his dismissal, had put his family's personal belongings into a storage facility at Burnside Industrial Park and then did not pay bills. As his belongings were being prepared for auction, formalin-fixed organs were found, and a Canada-wide arrest warrant for disrespect for human remains was issued by the Halifax Police. While the Alder Hey scandal resulted in a 535-page-long Parliamentary Report and the Human Tissue Act, van Velzen was never charged criminally in the UK. The largely unknown story of his second organ scandal in Halifax, is related here. Although he had obtained the body parts with the consent of the parents of the child to which they had belonged, his failure to properly identify and store them traumatized parents already impacted by his organ-hoarding in the UK, traumatized additional parents in Halifax, and resulted in significant waste of public resources in investigating the case. He pled guilty to "indignity to a human body" in Canada and was fined and placed on 12 months' probation.

Eosinophilic/T-cell chorionic vasculitis was initially defined as "a new form of chorionic vasculitis characterized by an infiltrate composed primarily of eosinophils and CD3(+) T lymphocytes ... [that] occurs in the absence of any evidence of chorioamnionitis." No subsequent reports have directly addressed whether histologic evidence suggestive of amniotic fluid infection should preclude its diagnosis. The case reported here describes a term placenta with mild acute chorionitis, moderate acute subchorionitis, mild acute chorionic vasculitis, and funisitis associated with multifocal eosinophilic/T-cell chorionic vasculitis. It shows unequivocally, with immunohistochemical staining, that eosinophilic/T-cell chorionic vasculitis and acute chorionic vasculitis can be seen and histologically distinguished in the same case. The paper shows how differing interpretations of inclusion and exclusion criteria by investigators have affected estimates of the incidence of this rare lesion. There is a need to harmonize diagnostic criteria; the report describes how cases with both entities can be documented carefully.

BACKGROUND:For patients undergoing rectal cancer surgery, we evaluated whether suboptimal preoperative surgeon evaluation of resection margins is a latent condition factor-a factor that is common, unrecognized, and may increase the risk of certain adverse events, including local tumour recurrence, positive surgical margin, nontherapeutic surgery, and in-hospital mortality.METHODS:In this observational case series of patients who underwent rectal cancer surgery during 2016 in Local Health Integrated Network 4 region of Ontario (population 1.4 million), chart review and a trigger tool were used to identify patients who experienced the adverse events. An expert panel adjudicated whether each event was preventable or nonpreventable and identified potential contributing factors to adverse events.RESULTS:Among 173 patients, 25 (14.5%) had an adverse event and 13 cases (7.5%) were adjudicated as preventable. Rate of surgeon awareness of preoperative margin status was low at 50% and similar among cases with and without an adverse event (p = 0.29). Suboptimal surgeon preoperative evaluation of surgical margins was adjudicated a contributing factor in all 11 preventable local recurrence, positive margin, and nontherapeutic surgery cases. Failure to rescue was judged a contributing factor in the two cases with preventable in-hospital mortality.CONCLUSIONS:Suboptimal surgeon preoperative evaluation of surgical margins in rectal cancer is likely a latent condition factor. Optimizing margin evaluation may be an efficient quality improvement target.

It has been widely reported by historians that physicians were aware of two distinct types of diabetes mellitus by the 1880s, and that these were both similar to and the direct forerunners of type 1, juvenile-onset and type 2, adult-onset diabetes. The writings of prominent specialist physicians practicing just prior to the discovery of insulin in 1921–1922 were reviewed and there is little evidence that experts believed that adult and childhood diabetes were different. In fact, more than a decade passed after the discovery of insulin before diabetes in children and adults even began to be distinguished. Childhood diabetes was exceedingly rare in the early 20th century and diabetes was believed to be primarily a chronic disease of adults. It is interesting to speculate about what might have happened if the first pancreatic extract tests had been performed on adult-onset diabetics with insulin-resistant diabetes mellitus. Clearly, the results would have been disappointing and the discovery of insulin delayed. This essay explores how the test subject decision was made. It is fortuitous that a 14 year old boy with what was unequivocally type 1 diabetes was selected to be the first insulin recipient, and the rest is history.

The authors thank Dr. Hatano for his letter to the editor in response to our paper, as this creates an opportunity for further dialog on an entity which appeared as a surprising finding in another paper on vitelline vessel remnants (VVRs); in that paper, acute inflammation arising from VVRs was seen in 70.3% of 37 cords with VVRs; cord cross-sections were stained with both H&E and CD15 immunostains and a complex grading/staging system was utilized to characterize the scope and distribution of infiltrates. When writing a follow-up paper which described two primary patterns of fetal circulation within VVRs, 70 new cases of cords with VVRs were studied and, as mentioned in the current paper, these same 70 cases were used in the study currently under discussion. Having found no advantage to CD15 immunostaining, we developed a simpler, H&E-based low vs high grade/stage system in the current paper. Some of the ”basic information” that Hatano describes as “missing” is provided in the longer paper using the same 70 cases. Other requested information is clinical and, since our study was purely histological, we did not have access to this information – nor was it needed to make our histological observations. Hatano et al. recently published a new CD15immunostain-based classification system for neutrophilic responses in umbilical cords. Overall, their method is highly resource-intensive, but we will focus only on the portion of their study related to VVR inflammation; they concluded the presence of CD15+ cells surrounding VVRs has “no clinical or pathological relevance ... as per statistical analysis.” Such a definitive statement cannot be justified after comparing groups with sample sizes of 3 (cases without vitelline vasculitis) and 19 (cases with vitelline vasculitis). According to their online Supplemental Table 2, only 3 of 22 placentas with VVRs also showed histologic evidence of acute chorioamnionitis; interestingly, all 3 cords had vitelline vasculitis and all cases with the presence of both a VVR and chorioamnionitis showed vitelline vasculitis. In our 4-fold larger study, we found VVR-derived funisitis had a sensitivity of 88% and specificity of 100% for histological evidence of amniotic fluid infection (AFI) in third-trimester placentas. Many of their clinical indicators that could logically be affected by AFI showed a supportive trend. Incidence of threatened premature delivery, frequency of threatened abortion, bacterial vaginosis, premature rupture of membranes, and elevated median maternal C-reactive protein were all higher among cases with vitelline vasculitis. Regardless, their “vitelline vasculitis” does not fully overlap with our “VVR-derived funisitis.” Hatano et al. relied upon CD15-staining, which is both too sensitive and not specific (figure). It should be noted that antibodies to CD15 also stain CD68+ macrophages, which are present in Wharton’s jelly, especially in the vicinity of VVRs. Figure 3 of their paper shows a paired VVR surrounded by some randomly scattered CD15+ cells, which could be macrophages. In our opinion, only neutrophils which are easily identified in Wharton’s jelly in H&E-stained sections matter. Furthermore, our data suggest that only high grade/stage VVR-derived funisitis, which requires the identification of neutrophils having migrated to the cord’s amniotic surface, has much likelihood of clinical significance. Adding further inaccuracy, their method of determining severity of vasculitis is based upon whether CD15+ cells are present in the intima (mild), the muscularis (moderate), or Wharton’s jelly (severe); while such a grading scheme may be applicable to umbilical arteries/veins, it is clearly not applicable to thin-walled VVRs, which do not have discrete layers; therefore, all of their “vitelline vasculitis” cases were graded as severe, including their Figure 3. Using H&Estained sections to identify neutrophils, our study found an incidence of 54.3%; of these cases, 61% were high grade/stage. Overdiagnosis (i.e., lack of specificity) and overestimation of severity explains both their astronomical incidence of 86.4% (19/22) and their belief that the finding, even if “severe,” is meaningless. As for the issue of diffusion distance raised by Hatano, VVRs normally reside within 1 mm of the cord’s amniotic surface, and so this is not an important variable.

Background: Workload measurement is important to help determine optimal staffing and workload distribution for pathology laboratories. The Level 4 Equivalent (L4E) System is the most widely used Anatomical Pathology (AP) workload measurement tool in Canada. However, it was initially not developed with subspecialties in mind. Methods: In 2016, a Pan-Canadian Pediatric-Perinatal Pathology Workload Committee (PCPPPWC) was organized to adapt the L4E System to assess Pediatric-Perinatal Pathology workload. Four working groups were formed. The Placental Pathology Working Group was tasked to develop a scheme for fair valuation of placental specimens signed out by subspecialists in the context of the L4E System. Previous experience, informal time and motion studies, a survey of Canadian Pediatric-Perinatal Pathologists, and interviews of Pathologists' Assistants (PA) informed the development of such scheme. Results: A workload measurement scheme with average L4E workload values for examination and reporting of singleton and multiple gestation placentas was proposed. The proposal was approved by the Canadian Association of Pathologist - Association canadienne des pathologistes Workload and Human Resources Committee for adoption into the L4E System. Conclusion: The development of a workload measurement model for placental specimens provides an average and fair valuation of these specimen types, enabling its use for resource planning and workload distribution.

Historians of diabetes have long claimed that physicians were aware of two distinct types of diabetes mellitus by the 1880s, and that these were the direct forerunners of type 1, juvenile-onset and type 2, adult-onset diabetes. French physician Étienne Lancereaux (1829-1910), based on autopsy and clinical studies, classified diabetes either as diabète maigre (thin, or more accurately emaciated, diabetes), which he believed to be pancreatic in origin with a poor prognosis, or diabète gras (fat diabetes), which he believed had a much better prognosis and was not pancreatic in origin. Historians citing Lancereaux have claimed that he observed the former to occur in young and the latter in middle-aged and elderly people. We review the papers of Lancereaux to clarify his clinical observations and understanding of diabetes. Lancereaux's description of diabète maigre bores little resemblance to juvenile diabetes and all of his thin patients were middle-aged or older. On the other hand, his diabète gras is akin to type 2 diabetes and he might well deserve credit for its characterization.

Introduction: Recurrence risk of villitis of unknown etiology (VUE) remains uncertain because of few studies and their methodologic limitations. We calculated recurrence risk in a large population of deliveries after minimizing important biases and compared it to others via systematic review and meta-analysis. Methods: Over 11 years of placenta pathology reports on singleton deliveries were retrieved and searched for 'villitis' or 'VUE'. Cases of acute villitis and chronic villitis from infections were eliminated via pathologist review. Reports were merged to data containing gestational age, parity and gravida. Recurrence risk of VUE per patient, per parity and per gravida was determined among patients with >= 2 placentas examined for deliveries >= 20 weeks gestation. Results were compared to those from articles and their references identified by a MEDLINE (R) search. Recurrence risks among methodologically similar studies were pooled using a random effects model. Results: Among 29 124 placenta pathology reports from 27 087 patients, there were 2423 cases of VUE among 2382 patients, of which 153 had >= 2 placentas examined. There were 41 recurrent cases of VUE for a recurrence risk of 27% per patient, 22% per parity, and 19% per gravida. We identified 64 articles, of which 4 were retained. One examined all placentas from all births over a similar to 3-year period, finding a recurrence risk of 27%. The remaining 3 studies, along with our own, used indications for placental examination and had a pooled recurrence risk of 30% (95% Confidence Interval: 0.21-0.41). Discussion: In our study, which is the largest, most comprehensive, and methodologically robust to date, VUE recurrence risk was similar to 30%.