Ectogenesis and the value of gestational ties.

Ectogenesis technology would make it possible to support the complete gestational development of a human being outside the female body. Proponents argue that this technology offers a welcome opportunity to expand reproductive options for those unable or unwilling to gestate. However, by completely bypassing pregnancy, the use of ectogenesis prevents the formation of gestational family ties. Consequently, it has faced criticism for perpetuating a patriarchal view of the family that undermines the moral significance of gestation. The concern is that the introduction of this technology might result in the loss of reproductive autonomy for those who desire to experience pregnancy, as they face pressures to opt for ectogenesis instead. Existing accounts of family values define parents' rights to rear a child, but they fail to establish a right to gestate that can protect an individual's interest in bearing a child. To provide a more comprehensive account of family values, I argue that pregnancy involves a unique quality of intimacy and can make distinct contributions to one's flourishing. Based on this premise, I defend a fundamental moral right to gestate that can help safeguard the option of pregnancy for those who desire it. In conclusion, I consider how a prospective gestator need not provide optimal conditions for fetal development in the way that ectogenesis promises in order for their choice of pregnancy to be justified.

Prognostic Value of BAP1 Protein Expression in Uveal Melanoma.

The prognostic value of the traditional pathologic parameters that form part of the American Joint Committee on Cancer staging system and genetic classifications using monosomy chromosome 3 and structural alterations in chromosome 8 are well established and are part of the diagnostic workup of uveal melanoma (UM). However, it has not been fully clarified whether nuclear protein expression of the tumor suppressor gene BAP1 (nBAP1) by immunohistochemistry alone is as powerful a predictor of overall survival (OS) and/or disease-specific survival (DSS) as chromosome analysis. The protein expression of nBAP1 was evaluated in a retrospective cohort study of 308 consecutive patients treated by primary enucleation between January 1974 and December 2022. We correlated clinical, pathologic, and cytogenetic characteristics to identify the best prognostic indicators for OS and DSS. Loss of nBAP1 was detected in 144/308 (47%) of patients. Loss of nBAP1 expression was significantly associated with poor survival. In patients with disomy chromosome 3, nBAP1 negative is significantly associated with poorer OS but not DSS. We observed that older age (>63 years), presence of metastasis, and nBAP1 negative remained independent prognostic factors in multivariate analysis. nBAP1 protein expression proved to be a more reliable prognostic indicator for OS than the American Joint Committee on Cancer staging, M3 status, or The Cancer Genome Atlas classification in this cohort. This study provides support for accurate prognostication of UM patients in routine histology laboratories by immunohistochemistry for nBAP1 alone.

Facilitating taxonomy and phylogenetics: An informative and cost-effective protocol integrating long amplicon PCRs and third-generation sequencing.

Phylogenetic inference has become a standard technique in integrative taxonomy and systematics, as well as in biogeography and ecology. DNA barcodes are often used for phylogenetic inference, despite being strongly limited due to their low number of informative sites. Also, because current DNA barcodes are based on a fraction of a single, fast-evolving gene, they are highly unsuitable for resolving deeper phylogenetic relationships due to saturation. In recent years, methods that analyse hundreds and thousands of loci at once have improved the resolution of the Tree of Life, but these methods require resources, experience and molecular laboratories that most taxonomists do not have. This paper introduces a PCR-based protocol that produces long amplicons of both slow- and fast-evolving unlinked mitochondrial and nuclear gene regions, which can be sequenced by the affordable and portable ONT MinION platform with low infrastructure or funding requirements. As a proof of concept, we inferred a phylogeny of a sample of 63 spider species from 20 families using our proposed protocol. The results were overall consistent with the results from approaches based on hundreds and thousands of loci, while requiring just a fraction of the cost and labour of such approaches, making our protocol accessible to taxonomists worldwide.

Attitudes toward COVID-19 restrictions and COVID-19-related stress and fear among college students across three waves.

Background and Aims: The COVID-19 pandemic has significantly impacted the mental health of college students, leading to increased psychological distress. This study explored potenital predictors to better understand the factors that influence and mitigate student COVID-19 stress in the evolving landscape of residential colleges. Specifically, we investigated the roles of COVID-19 fear, loneliness, and attitudes toward COVID-19 restrictions. Methods: Employing a longitudinal online survey design, we collected data over the fall 2020 semester from 122 first-year college students enrolled in a small mid-west liberal arts college. Participants completed the same survey three times: Wave 1 in August, Wave 2 in October, and Wave 3 in November. Results: Fear of COVID-19 (Time 1) was a significant predictor of increased COVID-19 related stress at both Time 2 and Time 3. Interestingly, loneliness (Time 1) moderated the effect of fear of COVID-19 (Time 1) on attitudes toward COVID-19 restrictions at Time 2. Moreover, students' negative attitudes toward COVID-19 restrictions and feelings of loneliness increased over the course of the semester. Conclusions: These findings suggest that college students' wellbeing in the context of COVID-19 stress is influenced by a complex interplay of perceptions of COVID-19 (stress, fear, attitudes) and feelings of social isolation (loneliness). Further research in this area is crucial to provide targeted support and interventions to promote students' mental health.

Multi-Omic, Histopathologic, and Clinicopathologic Effects of Once-Weekly Oral Rapamycin in a Naturally Occurring Feline Model of Hypertrophic Cardiomyopathy: A Pilot Study.

Hypertrophic cardiomyopathy (HCM) remains the single most common cardiomyopathy in cats, with a staggering prevalence as high as 15%. To date, little to no direct therapeutical intervention for HCM exists for veterinary patients. A previous study aimed to evaluate the effects of delayed-release (DR) rapamycin dosing in a client-owned population of subclinical, non-obstructive, HCM-affected cats and reported that the drug was well tolerated and resulted in beneficial LV remodeling. However, the precise effects of rapamycin in the hypertrophied myocardium remain unknown. Using a feline research colony with naturally occurring hereditary HCM (n = 9), we embarked on the first-ever pilot study to examine the tissue-, urine-, and plasma-level proteomic and tissue-level transcriptomic effects of an intermittent low dose (0.15 mg/kg) and high dose (0.30 mg/kg) of DR oral rapamycin once weekly. Rapamycin remained safe and well tolerated in cats receiving both doses for eight weeks. Following repeated weekly dosing, transcriptomic differences between the low- and high-dose groups support dose-responsive suppressive effects on myocardial hypertrophy and stimulatory effects on autophagy. Differences in the myocardial proteome between treated and control cats suggest potential anti-coagulant/-thrombotic, cellular remodeling, and metabolic effects of the drug. The results of this study closely recapitulate what is observed in the human literature, and the use of rapamycin in the clinical setting as the first therapeutic agent with disease-modifying effects on HCM remains promising. The results of this study establish the need for future validation efforts that investigate the fine-scale relationship between rapamycin treatment and the most compelling gene expression and protein abundance differences reported here.

A Review of the Molecular Landscape of Adenoid Cystic Carcinoma of the Lacrimal Gland.

Adenoid cystic carcinoma (ACC) has a worldwide incidence of three to four cases per million population. Although more cases occur in the minor and major salivary glands, it is the most common lacrimal gland malignancy. ACC has a low-grade, indolent histological appearance, but is relentlessly progressive over time and has a strong proclivity to recur and/or metastasise. Current treatment options are limited to complete surgical excision and adjuvant radiotherapy. Intra-arterial systemic therapy is a recent innovation. Recurrent/metastatic disease is common due to perineural invasion, and it is largely untreatable as it is refractory to conventional chemotherapeutic agents. Given the rarity of this tumour, the molecular mechanisms that govern disease pathogenesis are poorly understood. There is an unmet, critical need to develop effective, personalised targeted therapies for the treatment of ACC in order to reduce morbidity and mortality associated with the disease. This review details the evidence relating to the molecular underpinnings of ACC of the lacrimal gland, including the MYB-NFIB chromosomal translocations, Notch-signalling pathway aberrations, DNA damage repair gene mutations and epigenetic modifications.

Growth mindset of anxiety and avoidant coping as mediators of anxiety across the first year of college: A longitudinal survey of college students in the context of the COVID-19 pandemic.

Introduction: The purpose of this study was to evaluate the mediating role of growth mindset of anxiety beliefs and avoidant coping behaviors in predicting changes in anxiety across the first year of college, drawing from a sample of first year students managing the transition to college under the COVID-19 pandemic and associated restrictions (Fall 2020-Fall 2021). Methods: Self-report online surveys (n=122) were administered to first year students at four timepoints: the beginning (August 2020; T1), and follow up surveys at two months (October 2020; T2), three months (November 2020; T3) and twelve months (August 2021; T4). Results: Path analysis indicate that growth mindset of anxiety and avoidant coping partially mediate the relationship between baseline anxiety and later anxiety outcomes. Discussion: These findings have implications for mental health interventions designed to alter health attributions and mindset.

College transition Fall 2020 and 2021: Understanding the relationship of COVID-19 experiences and psychosocial correlates with anxiety and depression.

Rates of mental health symptoms, particularly anxiety and depression, have increased significantly in college students in the past decade along with utilization of mental health resources. The COVID-19 pandemic created an additional source of stressors to an already challenging landscape of college transition. COVID-19 has been associated with an increase of anxiety among college students, particularly first year students, entering college in Fall 2020. The shifts in policy (e.g., federal, state, and college) accruing medical data, and vaccine availability between Fall 2020 and Fall 2021 provide an opportunity to examine the role of COVID-19 experiences in the transition to college for these two first-year student cohorts. This study examined two cohorts of first-year students, Fall 2020 and 2021, to better understand the relationship between COVID-19 experiences, psychosocial correlates, and mental health symptoms. Results suggest that for students in our Fall 2020 cohort COVID-19 experiences played a distinct role in the prediction of mental health symptoms while in Fall 2021 COVID-19 experiences did not uniquely contribute to prediction of mental health symptoms. These findings have implications for mental health interventions for first-year students transitioning to college.

Multiple paths toward repeated phenotypic evolution in the spiny-leg adaptive radiation (Tetragnatha; Hawai'i).

The repeated evolution of phenotypes provides clear evidence for the role of natural selection in driving evolutionary change. However, the evolutionary origin of repeated phenotypes can be difficult to disentangle as it can arise from a combination of factors such as gene flow, shared ancestral polymorphisms or mutation. Here, we investigate the presence of these evolutionary processes in the Hawaiian spiny-leg Tetragnatha adaptive radiation, which includes four microhabitat-specialists or ecomorphs, with different body pigmentation and size (Green, Large Brown, Maroon, and Small Brown). We investigated the evolutionary history of this radiation using 76 newly generated low-coverage, whole-genome resequenced samples, along with phylogenetic and population genomic tools. Considering the Green ecomorph as the ancestral state, our results suggest that the Green ecomorph likely re-evolved once, the Large Brown and Maroon ecomorphs evolved twice and the Small Brown evolved three times. We found that the evolution of the Maroon and Small Brown ecomorphs likely involved ancestral hybridization events, while the Green and Large Brown ecomorphs likely evolved through novel mutations, despite a high rate of incomplete lineage sorting in the dataset. Our findings demonstrate that the repeated evolution of ecomorphs in the Hawaiian spiny-leg Tetragnatha is influenced by multiple evolutionary processes.

Protein Tyrosine Phosphatase Non-Receptor 11 (PTPN11/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC).

PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates the mitogen-activated protein kinase (MAPK) pathway upstream of KRAS and MEK. PTPN11/Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, the role of mutated PTPN11 in lung cancer tumourigenesis and its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from the tumour and matched the normal tissue of 356 NSCLC patients (98 adenocarcinomas (LUAD) and 258 squamous cell carcinomas (LUSC)). Further, PTPN11 mutation cases were identified in additional cohorts, including TCGA, Broad, and MD Anderson datasets and the COSMIC database. PTPN11 constructs harbouring PTPN11 E76A, A72D and C459S mutations were stably expressed in IL-3 dependent BaF3 cells and NSCLC cell lines (NCI-H1703, NCI-H157, NCI-H1299). The MAPK and PI3K pathway activation was evaluated using Western blotting. PTPN11/Shp2 phosphatase activity was measured in whole-cell protein lysates using an Shp2 assay kit. The Shp2 inhibitor (SHPi) was assessed both in vitro and in vivo in a PTPN11-mutated cell line for improved responses to MAPK and PI3K targeting therapies. Somatic PTPN11 hotspot mutations occurred in 4/98 (4.1%) adenocarcinomas and 7/258 (2.7%) squamous cells of 356 NSCLC patients. Additional 26 PTPN11 hotspot mutations occurred in 23 and 3 adenocarcinomas and squamous cell carcinoma, respectively, across the additional cohorts. Mutant PTPN11 significantly increased the IL-3 independent survival of Ba/F3 cells compared to wildtype PTPN11 (p < 0.0001). Ba/F3, NCI-H1703, and NCI-H157 cells expressing mutant PTPN11 exhibited increased PTPN11/Shp2 phosphatase activity and phospho-ERK1/2 levels compared to cells expressing wildtype PTPN11. The transduction of the PTPN11 inactivating mutation C459S into NSCLC cell lines led to decreased phospho-ERK, as well as decreased phospho-AKT in the PTPN11-mutated NCI-H661 cell line. NCI-H661 cells (PTPN11-mutated, KRAS-wild type) were significantly more sensitive to growth inhibition by the PI3K inhibitor copanlisib (IC50: 13.9 ± 4.7 nM) compared to NCI-H1703 (PTPN11/KRAS-wild type) cells (IC50: >10,000 nM). The SHP2 inhibitor, in combination with the PI3K targeting therapy copanlisib, showed no significant difference in tumour development in vivo; however, this significantly prevented MAPK pathway induction in vitro (p < 0.0001). PTPN11/Shp2 demonstrated the in vitro features of a driver oncogene and could potentially sensitize NSCLC cells to PI3K inhibition and inhibit MAPK pathway activation following PI3K pathway targeting.

Delayed-release rapamycin halts progression of left ventricular hypertrophy in subclinical feline hypertrophic cardiomyopathy: results of the RAPACAT trial.

OBJECTIVE: Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM. ANIMALS: 43 client-owned cats with subclinical HCM. METHODS: Cats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA. RESULTS: No demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups. CLINICAL RELEVANCE: Results demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.

STI Testing among Medicaid Enrollees Initiating PrEP for HIV Prevention in Six Southern States.

OBJECTIVES: The purpose of this study was to measure sexually transmitted infection (STI) testing among Medicaid enrollees initiating preexposure prophylaxis (PrEP) to prevent human immunodeficiency virus. Secondary data are in the form of Medicaid enrollment and claims data in six states in the US South. METHODS: Research partnerships in six states in the US South developed a distributed research network to accomplish study aims. Each state identified all first-time PrEP users in fiscal year 2017-2018 (combined N = 990) and measured the presence of STI testing for chlamydia, syphilis, and gonorrhea through 2019. Each state calculated the percentage of individuals with at least one STI test during 3-, 6-, and 12-month follow-up periods. RESULTS: The proportion of first-time PrEP users that received an STI test varied by state: 37% to 67% of all of the individuals in each state who initiated PrEP received a test within the first 6 months of PrEP treatment and 50% to 77% received a test within the first 12 months. CONCLUSIONS: Although the Centers for Disease Control and Prevention recommends STI testing at least every 6 months for PrEP users, our analysis of Medicaid data suggests that STI testing occurs less frequently than recommended in populations at elevated risk of syphilis, gonorrhea, and chlamydia.

Use of residential opioid use disorder treatment among Medicaid enrollees in nine states.

INTRODUCTION: Residential treatment is a key component of the opioid use disorder care continuum, but research has not measured well the differences in its use across states at the enrollee level. METHODS: This cross-sectional observational study used Medicaid claims data from nine states to document the prevalence of residential treatment for opioid use disorder and to describe the characteristics of patients receiving care. For each patient characteristic, chi-square and t-tests tested for differences in the distribution between individuals who did and did not receive residential care. RESULTS: Among 491,071 Medicaid enrollees with opioid use disorder, 7.5 % were treated in residential facilities in 2019, though this number ranged widely (0.3-14.6 %) across states. Residential patients were more likely to be younger, non-Hispanic White, male, and living in an urban area. Although residential patients were less likely than those without residential care to be eligible for Medicaid through disability, diagnoses for comorbid conditions were more frequently observed among residential patients. CONCLUSIONS: Results from this large, multi-state study add context to the ongoing national conversation around opioid use disorder treatment and policy, providing a baseline for future work.

Prenatal syphilis screening among pregnant Medicaid enrollees by sexually transmitted infection history as well as race and ethnicity.

BACKGROUND: Congenital syphilis can cause severe morbidity, including miscarriage and stillbirth, and rates are increasing rapidly within the United States. However, congenital syphilis can be prevented with early detection and treatment of syphilis during pregnancy. Current screening recommendations propose that all women should be screened early in pregnancy, whereas women with elevated risks for congenital syphilis should be screened again later in pregnancy. The rapid increase in congenital syphilis rates suggests that there are still gaps in prenatal syphilis screening. OBJECTIVE: This study aimed to examine associations between the odds of prenatal syphilis screening and sexually transmitted infection history or other patient characteristics across 3 states with elevated rates of congenital syphilis. STUDY DESIGN: We used the Medicaid claims data from Kentucky, Louisiana, and South Carolina for women with deliveries between 2017 and 2021. Within each state, we examined the log-odds of prenatal syphilis screening as a function of the mother's health history, demographic factors, and Medicaid enrollment history. Patient history was established using a 4-year lookback period of the Medicaid claims data; in state A, sexually transmitted infection surveillance data were used to improve the sexually transmitted infection history. RESULTS: The prenatal syphilis screening rates varied by state, ranging from 62.8% to 85.1% of deliveries to women without a recent history of sexually transmitted infections and from 78.1% to 91.1% of deliveries to women with a previous sexually transmitted infection. For the main outcome of syphilis screening at any time during pregnancy, deliveries associated with previous sexually transmitted infections had 1.09 to 1.37 times higher adjusted odds ratios of undergoing screening. Deliveries to women with continuous Medicaid coverage throughout the first trimester also had higher odds of syphilis screening at any time (adjusted odds ratio, 2.45-3.15). Among deliveries to women with a previous sexually transmitted infection, only 53.6% to 63.6% underwent first-trimester screening and this rate was still just 55.0% to 69.5% when considering only deliveries to women with a previous sexually transmitted infection and full first-trimester Medicaid coverage. Fewer delivering women underwent third-trimester screening (20.3%-55.8% of women with previous sexually transmitted infection). Compared with deliveries to White women, deliveries to Black women had lower odds of first-trimester screening (adjusted odds ratio, 0.85 in all states) but higher odds of third-trimester screening (adjusted odds ratio, 1.23-2.03), potentially impacting maternal and birth outcomes. For state A, linkage to surveillance data doubled the rate of detection of a previous sexually transmitted infection because 53.0% of deliveries by women with a previous sexually transmitted infection would not have had sexually transmitted infection history detected using Medicaid claims alone. CONCLUSION: A previous sexually transmitted infection and continuous preconception Medicaid enrollment were associated with higher rates of syphilis screening, but Medicaid claims alone do not fully capture the sexually transmitted infection history of patients. The overall screening rates were lower than would be expected given that all women should undergo prenatal screening, but the rates in the third trimester were particularly low. Of note, there are gaps in early screening for non-Hispanic Black women who had lower odds of first-trimester screening when compared with non-Hispanic White women despite being at elevated risk for syphilis.

Association of polysubstance use disorder with treatment quality among Medicaid beneficiaries with opioid use disorder.

INTRODUCTION: The opioid crisis is transitioning to a polydrug crisis, and individuals with co-occurring substance use disorder (SUDs) often have unique clinical characteristics and contextual barriers that influence treatment needs, engagement in treatment, complexity of treatment planning, and treatment retention. METHODS: Using Medicaid data for 2017-2018 from four states participating in a distributed research network, this retrospective cohort study documents the prevalence of specific types of co-occurring SUD among Medicaid enrollees with an opioid use disorder (OUD) diagnosis, and assesses the extent to which different SUD presentations are associated with differential patterns of MOUD and psychosocial treatments. RESULTS: We find that more than half of enrollees with OUD had a co-occurring SUD, and the most prevalent co-occurring SUD was for "other psychoactive substances", indicated among about one-quarter of enrollees with OUD in each state. We also find some substantial gaps in MOUD treatment receipt and engagement for individuals with OUD and a co-occurring SUD, a group representing more than half of individuals with OUD. In most states, enrollees with OUD and alcohol, cannabis, or amphetamine use disorder are significantly less likely to receive MOUD compared to enrollees with OUD only. In contrast, enrollees with OUD and other psychoactive SUD were significantly more likely to receive MOUD treatment. Conditional on MOUD receipt, enrollees with co-occurring SUDs had 10 % to 50 % lower odds of having a 180-day period of continuous MOUD treatment, an important predictor of better patient outcomes. Associations with concurrent receipt of MOUD and behavioral counseling were mixed across states and varied depending on co-occurring SUD type. CONCLUSIONS: Overall, ongoing progress toward increasing access to and quality of evidence-based treatment for OUD requires further efforts to ensure that individuals with co-occurring SUDs are engaged and retained in effective treatment. As the opioid crisis evolves, continued changes in drug use patterns and populations experiencing harms may necessitate new policy approaches that more fully address the complex needs of a growing population of individuals with OUD and other types of SUD.

Richness and resilience in the Pacific: DNA metabarcoding enables parallelized evaluation of biogeographic patterns.

Islands make up a large proportion of Earth's biodiversity, yet are also some of the most sensitive systems to environmental perturbation. Biogeographic theory predicts that geologic age, area, and isolation typically drive islands' diversity patterns, and thus potentially impact non-native spread and community homogenization across island systems. One limitation in testing such predictions has been the difficulty of performing comprehensive inventories of island biotas and distinguishing native from introduced taxa. Here, we use DNA metabarcoding and statistical modelling as a high throughput method to survey community-wide arthropod richness, the proportion of native and non-native species, and the incursion of non-natives into primary habitats on three archipelagos in the Pacific - the Ryukyus, the Marianas and Hawaii - which vary in age, isolation and area. Diversity patterns largely match expectations based on island biogeography theory, with the oldest and most geographically connected archipelago, the Ryukyus, showing the highest taxonomic richness and lowest proportion of introduced species. Moreover, we find evidence that forest habitats are more resilient to incursions of non-natives in the Ryukyus than in the less taxonomically rich archipelagos. Surprisingly, we do not find evidence for biotic homogenization across these three archipelagos: the assemblage of non-native species on each island is highly distinct. Our study demonstrates the potential of DNA metabarcoding to facilitate rapid estimation of biogeographic patterns, the spread of non-native species, and the resilience of ecosystems.

Verification and validation of the anti-PD-L1 antibody, Clone 22C3 on a laboratory-developed test.

AIMS: The first aim of this study is to compare and validate the performance of the programmed death receptor ligand 1 (PD-L1) IHC 22C3 pharmDx assay kit processed via Dako Omnis platform with the Dako Autostainer Link 48. The second aim is to examine the concordance of scoring by pathologists using the same immunohistochemistry (IHC) assay on the Dako Omnis platform and the Dako Autostainer Link 48. METHODS: Fourty-seven formalin-fixed, paraffin-embedded tissue blocks of head and neck squamous cell carcinoma tumour were stained with the PD-L1 IHC 22C3 pharmDx assay kit processed via the Dako Autostainer Link 48 and the Dako Omnis platform. Combined positive score (CPS) was ascribed by two scoring pathologists, with discordant cases provided with an agreed score. RESULTS: First, identical staining patterns were identified. Second, high agreement of PD-L1 scores when a CPS cut-off of 1 was implemented illustrated an overall agreement of 94%, positive agreement of 100% and negative agreement of 88%. Finally, results highlight an intraexaminer concordance of 89% and interexaminer concordance of 85% and 92%. CONCLUSIONS: In conclusion, we propose to open for discussion the deconstruction of the current practice of a compulsory companion diagnostic test (CDT) for a particular PD-L1 immunohistochemical assay. The implementation of laboratory developed tests as an alternative to the CDT poses as a novel and readily available method to surmount limitations posed to pathology laboratories.

Recurrent lacrimal gland pleomorphic adenoma.

Pleomorphic adenoma is the most common tumour of the lacrimal gland. Correct preoperative diagnosis is essential as the tumour should be removed en bloc. Incisional biopsy is contraindicated due to risk of recurrence and subsequent risk of malignancy. We identified 13 patients who were diagnosed with lacrimal gland pleomorphic adenoma in our institution over a 31-year period from 1990 to 2021. Of these, we describe four patients, three males and one female, who underwent incisional biopsy. One of these patients had a number of recurrences and required an orbital exenteration. The other two were treated with radiation to the orbit and experienced severe dry eye post-radiotherapy. All three patients are currently disease-free. The fourth patient underwent an incisional biopsy of his lacrimal gland pleomorphic adenoma (LGPA) within the last 6 months and has been referred for radiotherapy. The reasons for a lack of preoperative diagnosis of LGPA included clinical uncertainty and broad radiologic differential. None of the patients who had an en bloc resection experienced recurrence. We recommend that a fine needle aspirate (FNA) biopsy in lieu of a tissue biopsy should be performed where LGPA is included in the clinical and radiological differential diagnosis. If incisional biopsy is required, the suture track should be marked so that the entire biopsy track is removed with the specimen.