Transient Covalent Polymers through Carbodiimide-driven Assembly.

Biochemical systems make use of out-of-equilibrium polymers generated under kinetic control. Inspired by these systems, many abiotic supramolecular polymers driven by chemical fuel reactions have been reported. Conversely, polymers based on transient covalent bonds have received little attention, even though they have the potential to complement supramolecular systems by generating transient structures based on stronger bonds and by offering a straightforward tuning of reaction kinetics. In this study, we show that simple aqueous dicarboxylic acids give poly(anhydrides) when treated with the carbodiimide EDC. Transient covalent polymers with molecular weights exceeding 15,000 are generated which then decompose over the course of hours to weeks. Disassembly kinetics can be controlled using simple substituent effects in the monomer design. The impact of solvent polarity, carbodiimide concentration, temperature, pyridine concentration, and monomer concentration on polymer properties and lifetimes has been investigated. The results reveal substantial control over polymer assembly and disassembly kinetics, highlighting the potential for fine-tuned kinetic control in nonequilibrium polymerization systems.

Live-Attenuated Vaccines in Pediatric Solid Organ Transplant.

Measles, mumps, rubella (MMR), and varicella incidence rates have increased due to the delayed vaccination schedules of children secondary to the COVID-19 pandemic. Decreased herd immunity creates a risk for immunocompetent children and immunocompromised individuals in the community. Historically, live-attenuated vaccines (MMR and varicella) were recommended before solid organ transplants. The amount of time before transplant when this is appropriate is often debated, as is the utility of vaccine titers. MMR and varicella vaccines previously were not recommended in immunocompromised patients post-solid organ transplant due to the undue risk of transmission and posed infection risk. The new literature on live-attenuated vaccines in post-transplant pediatric patients provides more insight into the vaccines' safety and efficacy. The present article aims to provide guidance on live-attenuated vaccines (MMR and varicella) in the pre-transplant and post-operative solid organ transplant phases of care in pediatric patients.

Improved Risk-Stratification Scheme for Mismatch-Repair Proficient Stage II Colorectal Cancers Using the Digital Pathology Biomarker QuantCRC.

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

Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children.

Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.

A case-control autopsy series of liver pathology associated with novel coronavirus disease (COVID-19).

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) is most well-known for causing pulmonary injury, a significant proportion of patients experience hepatic dysfunction. The mechanism by which SARS-CoV2 causes liver injury is not fully understood. The goal of this study was to describe the hepatic pathology in a large cohort of deceased patients with COVID-19 as compared to a control group of deceased patients without COVID-19. METHODS: Consented autopsy cases at two institutions were searched for documentation of COVID-19 as a contributing cause of death. A group of consecutive consented autopsy cases during the same period, negative for SARS-CoV-2 infection, was used as a control group. The autopsy report and electronic medical records were reviewed for relevant clinicopathologic information. H&E-stained liver sections from both groups were examined for pertinent histologic features. Select cases underwent immunohistochemical staining for CD 68 and ACE2 and droplet digital polymerase chain reaction (ddPCR) assay for evaluation of SARS-CoV2 RNA. RESULTS: 48 COVID-19 positive patients (median age 73, M:F 3:1) and 40 COVID-19 negative control patients (median age 67.5, M:F 1.4:1) were included in the study. The COVID-19 positive group was significantly older and had a lower rate of alcoholism and malignancy, but there was no difference in other comorbidities. The COVID-19 positive group was more likely to have received steroids (75.6 % vs. 36.1 %, p < 0.001). Hepatic vascular changes were seen in a minority (10.6 %) of COVID-19 positive cases. When all patients were included, there were no significant histopathologic differences between groups, but when patients with chronic alcoholism were excluded, the COVID-19 positive group was significantly more likely to have steatosis (80.9 % vs. 50.0 %, p = 0.004) and lobular inflammation (45.7 % vs. 20.7 %, p = 0.03). Testing for viral RNA by ddPCR identified 2 of the 18 (11.1 %) COVID-19 positive cases to have SARS-CoV-2 RNA detected within the liver FFPE tissue. CONCLUSIONS: The most significant findings in the liver of COVID-19 positive patients were mild lobular inflammation and steatosis. The high rate of steroid therapy in this population may be a possible source of steatosis. Hepatic vascular alterations were only identified in a minority of patients and did not appear to play a predominant role in COVID-19 mediated hepatic injury. Low incidence of SARS-CoV-2 RNA positivity in liver tissue in our cohort suggests hepatic injury in the setting of COVID-19 may be secondary in nature.

Efficacy of Robotic Bronchoscopy for Molecular Marker Analysis in Primary Lung Cancer.

BACKGROUND: Molecular testing has become a more frequent necessity in NSCLC management. Using next-generation sequencing, multiple targets for therapy can be identified with small amounts of nuclear material. The authors evaluated the performance of robotic-assisted bronchoscopy in acquiring tissue that meets pre-analytic criteria for PD-L1 immunohistochemistry and/or next-generation sequencing. MATERIALS AND METHODS: Patients with a diagnosis of primary lung cancer identified through robotic bronchoscopy were retrospectively reviewed. Pathology reports were assessed for results of molecular testing and detection of programmed death-ligand 1 (PD-L1). An independent pathologist evaluated each specimen type (smears, cell block, tissue biopsy, and/or touch prep) to determine whether each tissue type would meet pre-analytic criteria for attempting next-generation sequencing and/or PD-L1 immunohistochemistry. RESULTS: Seventy-eight patients with primary lung were reviewed. By independent pathologic assessment of cytological smears, cell block, biopsy, and/or touch preparations, 72% of samples were found to be adequate for molecular and PD-L1 testing. Preanalytic adequacy (%) for next-generation sequencing (NGS) and PD-L1 staining was determined based on specimen type: cytological smear 48.6% for NGS; cell block 14.3% for NGS and 32.9% for PD-L1; biopsy 29.2% for NGS and 62.5% for PD-L1; and touch prep 61.4% for NGS. CONCLUSION: Robotic-assisted bronchoscopy yielded samples that met preanalytic criteria for molecular testing in 72% of cases. These results support the use of robotic-assisted bronchoscopy for both the diagnosis and molecular testing of early-stage lung cancer.

Successful Eradication of a Highly Resistant Elizabethkingia anophelis Species in a Premature Neonate With Bacteremia and Meningitis.

Elizabethkingia anophelis is a Gram-negative bacillus that can exhibit highly resistant phenotypes against most antibiotics with evidence of efficacy and safety in the neonatal population. Given the limited antimicrobial options, clinicians may be forced into challenging treatment scenarios when faced with central nervous system infections in premature neonates caused by E. anophelis . We report a case of successful treatment of hospital-acquired meningitis and bacteremia caused by E. anophelis at 11 days of life in a male infant born at 29 weeks, 1 day gestation and birth weight of 1.41 kg. Therapy consisted of vancomycin, dose adjusted to maintain goal troughs of 15-20 mg/L, and rifampin 10 mg/kg/dose every 12 hours, with ciprofloxacin 15 mg/kg/dose every 12 hours and trimethoprim/sulfamethoxazole 5 mg/kg/dose every 12 hours added due to antimicrobial susceptibilities and unsatisfactory response, for a total of 21 days. Following initiation of this multidrug regimen, repeat cultures were negative, laboratory parameters improved [with exception of elevated cerebrospinal fluid (CSF) white blood cell count], the patient remained otherwise stable, and there were no adverse effects noted from therapy. Complications after treatment included the requirement of bilateral hearing aids and the development of hydrocephalus necessitating ventriculoperitoneal shunt placement. To our knowledge, we report the first case of meningitis in a premature neonate initially identified as E. anophelis in the United States treated with this regimen which led to successful microbiologic eradication with no antimicrobial safety concerns.

Replacement of saturated fatty acids with linoleic acid in western diet attenuates atherosclerosis in a mouse model with inducible ablation of hepatic LDL receptor.

Dietary saturate fatty acids (SFAs) have been consistently linked to atherosclerosis and obesity, both of which are characterized by chronic inflammation and impaired lipid metabolism. In comparison, the effects of linoleic acid (LA), the predominant polyunsaturated fatty acid in the Western diet, seem to diverge. Data from human studies suggest a positive association between high dietary intake of LA and the improvement of cardiovascular risk. However, excessive LA intake has been implicated in the development of obesity. Concerns have also been raised on the potential pro-inflammatory properties of LA metabolites. Herein, by utilizing a mouse model with liver-specific Ldlr knockdown, we directly determined the effects of replacing SFAs with LA in a Western diet on the development of obesity and atherosclerosis. Specifically, mice treated with a Ldlr ASO were placed on a Western diet containing either SFA-rich butter (WD-B) or LA-rich corn oil (WD-CO) for 12 weeks. Despite of showing no changes in body weight gain or adiposity, mice on WD-CO exhibited significantly less atherosclerotic lesions compared to those on WD-B diet. Reduced lesion formation in the WD-CO-fed mice corresponded with a reduction of plasma triglyceride and cholesterol content, especially in VLDL and LDL, and ApoB protein levels. Although it increased expression of proinflammatory cytokines TNF-α and IL-6 in the liver, WD-CO did not appear to affect hepatic injury or damage when compared to WD-B. Collectively, our results indicate that replacing SFAs with LA in a Western diet could reduce the development of atherosclerosis independently of obesity.

Evaluation of automated sample preparation system for lymph node sampling.

Background: Endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-FNA) has revolutionized the diagnostic and staging approach to non-small cell carcinoma and thoracic lymphadenopathy. However, obstacles to efficacy of rapid on-site evaluation (ROSE) of the samples include variability in sample quality and slow and cumbersome process in the procedure room leading to extended procedure time. The purpose of this pilot study was to evaluate the feasibility and specimen quality of lymph node biopsies prepared through a novel automated system for automated fixation, drying and staining compared to standard slide preparation method. Methods: We performed a prospective, single-center pilot feasibility study of patients undergoing EBUS. Samples were split into conventional standard of care (SOC) slide preparation and preparation using the device ("instrument"). Pathologists compared the SOC slides to the slides prepared by the automated system and assessed the following metrics: nuclear and cytoplasmic quality, presence of debris/artifact, staining quality, creation of a monolayer, and ease of adequacy/diagnosis assessment. A score between 1 (lowest quality) and 3 (highest quality) was assigned to the above metrics. Results: Sixty patients were recruited. One to three lymph nodes were sampled for each patient for a total of 72 samples collected. The mean scores of each assessment category showed no statistical difference between the two preparation techniques except for improved monolayer creation in the instrument samples. Thirty of thirty-one (96.8%) paired samples in the final analysis showed diagnostic equivalency between the automated slides and conventional slides; the discordant pairing was reported to be suspicious on the instrument sample and atypical on the SOC. Conclusions: Study results suggest that slides prepared by the automated system are of adequate quality for adequacy assessment with diagnostic concordance when compared to SOC slides.

Performance of an Artificial Intelligence Model for Recognition and Quantitation of Histologic Features of Eosinophilic Esophagitis on Biopsy Samples.

We have developed an artificial intelligence (AI)-based digital pathology model for the evaluation of histologic features related to eosinophilic esophagitis (EoE). In this study, we evaluated the performance of our AI model in a cohort of pediatric and adult patients for histologic features included in the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). We collected a total of 203 esophageal biopsy samples from patients with mucosal eosinophilia of any degree (91 adult and 112 pediatric patients) and 10 normal controls from a prospectively maintained database. All cases were assessed by a specialized gastrointestinal (GI) pathologist for features in the EoEHSS at the time of original diagnosis and rescored by a central GI pathologist (R.K.M.). We subsequently analyzed whole-slide image digital slides using a supervised AI model operating in a cloud-based, deep learning AI platform (Aiforia Technologies) for peak eosinophil count (PEC) and several histopathologic features in the EoEHSS. The correlation and interobserver agreement between the AI model and pathologists (Pearson correlation coefficient [rs] = 0.89 and intraclass correlation coefficient [ICC] = 0.87 vs original pathologist; rs = 0.91 and ICC = 0.83 vs central pathologist) were similar to the correlation and interobserver agreement between pathologists for PEC (rs = 0.88 and ICC = 0.91) and broadly similar to those for most other histologic features in the EoEHSS. The AI model also accurately identified PEC of >15 eosinophils/high-power field by the original pathologist (area under the curve [AUC] = 0.98) and central pathologist (AUC = 0.98) and had similar AUCs for the presence of EoE-related endoscopic features to pathologists' assessment. Average eosinophils per epithelial unit area had similar performance compared to AI high-power field-based analysis. Our newly developed AI model can accurately identify, quantify, and score several of the main histopathologic features in the EoE spectrum, with agreement regarding EoEHSS scoring which was similar to that seen among GI pathologists.

Remotely operated robotic microscopy for rapid diagnosis of bronchoscopic cytology specimens.

BACKGROUND: Obtaining a diagnosis and treating pulmonary malignancies during the same anesthesia requires either an on-site pathologist or a system for remotely evaluating microscopic images. Cytology specimens are challenging to remotely assess given the need to navigate through dispersed and three-dimensional cell clusters. Remote navigation is possible using robotic telepathology, but data are limited on the ease of use of current systems, particularly for pulmonary cytology. METHODS: Air dried modified Wright-Giemsa stained slides from 26 touch preparations of transbronchial biopsies and 27 smears of endobronchial ultrasound guided fine needle aspirations were scored for ease of adequacy assessment and ease of diagnosis on robotic (rmtConnect Microscope) and non-robotic telecytology platforms. Diagnostic classifications were compared between glass slides and the robotic and non-robotic telecytology assessments. RESULTS: Compared to non-robotic telecytology, robotic telecytology had a greater ease of adequacy assessment and non-inferior ease of diagnosis. The median time to diagnosis using robotic telecytology was 85 s (range 28-190 s). Diagnostic categories were concordant for 76% of cases in robotic versus non-robotic telecytology and 78% of cases in robotic telecytology versus glass slide diagnosis. Weighted Cohen's kappa scores for agreement in these comparisons were 0.84 and 0.72, respectively. CONCLUSIONS: Use of a remote-controlled robotic microscope improved the ease of adequacy assessment compared to non-robotic telecytology and enabled strongly concordant diagnoses to be expediently rendered. This study provides evidence that modern robotic telecytology is a feasible and user-friendly method of remotely and potentially intraoperatively rendering adequacy assessments and diagnoses on bronchoscopic cytology specimens.

Digital Hepatic Iron Content: An Artificial Intelligence Model for Spatially Resolved Histologic Iron Quantitative Analysis in Liver Samples.

Currently, the precise evaluation of tissue hepatic iron content (HIC) requires laboratory testing using tissue-destructive methods based on colorimetry or spectrophotometry. To maximize the use of routine histologic stains in this context, we developed an artificial intelligence (AI) model for the recognition and spatially resolved measurement of iron in liver samples. Our AI model was developed using a cloud-based, supervised deep learning platform (Aiforia Technologies). Using digitized Pearl Prussian blue iron stain whole slide images representing the full spectrum of changes seen in hepatic iron overload, our training set consisted of 59 cases, and our validation set consisted of 19 cases. The study group consisted of 98 liver samples from 5 different laboratories, for which tissue quantitative analysis using inductively coupled plasma mass spectrometry was available, collected between 2012 and 2022. The correlation between the AI model % iron area and HIC was Rs = 0.93 for needle core biopsy samples (n = 73) and Rs = 0.86 for all samples (n = 98). The digital hepatic iron index (HII) was highly correlated with HII > 1 (area under the curve [AUC] = 0.93) and HII > 1.9 (AUC = 0.94). The percentage area of iron within hepatocytes (vs Kupffer cells and portal tract iron) identified patients with any hereditary hemochromatosis-related mutations (either homozygous or heterozygous) (AUC = 0.65, P = .01) with at least similar accuracy than HIC, HII, and any histologic iron score. The correlation between the Deugnier and Turlin score and the AI model % iron area for all patients was Rs = 0.87 for total score, Rs = 0.82 for hepatocyte iron score, and Rs = 0.84 for Kupffer cell iron score. Iron quantitative analysis using our AI model was highly correlated with both detailed histologic scoring systems and tissue quantitative analysis using inductively coupled plasma mass spectrometry and offers advantages (related to the spatial resolution of iron analysis and the nontissue-destructive nature of the test) over standard quantitative methods.

Artificial intelligence-based reticulin proportionate area - a novel histological outcome predictor in hepatocellular carcinoma.

AIMS: Reticulin stain is used routinely in the histological evaluation of hepatocellular carcinoma (HCC). The goal of this study was to assess whether the histological reticulin proportionate area (RPA) in HCCs predicts tumour-related outcomes. METHODS AND RESULTS: We developed and validated a supervised artificial intelligence (AI) model that utilises a cloud-based, deep-learning AI platform (Aiforia Technologies, Helsinki, Finland) to specifically recognise and quantify the reticulin framework in normal livers and HCCs using routine reticulin staining. We applied this reticulin AI model to a cohort of consecutive HCC cases from patients undergoing curative resection between 2005 and 2015. A total of 101 HCC resections were included (median age = 68 years, 64 males, median follow-up time = 49.9 months). AI model RPA reduction of > 50% (compared to normal liver tissue) was predictive of metastasis [hazard ratio (HR) = 3.76, P = 0.004, disease-free survival (DFS, HR = 2.48, P < 0.001) and overall survival (OS), HR = 2.80, P = 0.001]. In a Cox regression model, which included clinical and pathological variables, RPA decrease was an independent predictor of DFS and OS and the only independent predictor of metastasis. Similar results were found in the moderately differentiated HCC subgroup (WHO grade 2), in which reticulin quantitative analysis was an independent predictor of metastasis, DFS and OS. CONCLUSION: Our data indicate that decreased RPA is a strong predictor of various HCC-related outcomes, including within the moderately differentiated subgroup. Reticulin, therefore, may represent a novel and important prognostic HCC marker, to be further explored and validated.

TRPS1 outperforms GATA3 in pleural effusions with metastatic breast carcinoma versus mesothelioma.

INTRODUCTION: In evaluating malignant pleural fluid cytology, metastatic adenocarcinomas and mesotheliomas are often differential diagnoses. GATA binding protein 3 (GATA3) has historically been used to confirm metastatic breast carcinomas; however, GATA3 has low specificity if mesothelioma is included in differential diagnoses. Trichorhinophalangeal syndrome type 1 (TRPS1) protein is expressed in all types of breast carcinomas, with reported high specificity and sensitivity. We investigated the performance of TRPS1 immunohistochemistry (IHC) and compared it to GATA3 in pleural fluids diagnosed with metastatic breast carcinoma and mesothelioma. METHODS: Thirty-six consecutive ThinPrep pleural fluids and 4 pleural fine needle aspirations (FNAs) with diagnoses of metastatic breast carcinoma (21) and mesothelioma (19) were retrieved, and IHC with TRPS1 and GATA3 was performed on all. Immunoreactivity scores for TRPS1 were calculated by multiplying percentage of immunoreactive cells by staining intensity. Immunoreactivity scores were negative if 0 or 1, low positive if 2, intermediate positive if 3 or 4, or high positive if 6 or 9. Nuclear immunoreactivity of ≥10% with at least moderate intensity was judged GATA3 positive. RESULTS: GATA3 showed immunoreactivity in all metastatic breast carcinomas and 84% of mesotheliomas. TRPS1 was immunoreactive in all breast carcinoma cases (18 with a score of 9 and 3 with a score of 6). TRPS1 showed low positivity in 5% of mesothelioma cases with all other cases being negative. CONCLUSION: When cytomorphologic differential diagnoses of mesothelioma exist, TRPS1 is a more specific marker than GATA3 for confirmation of metastatic breast carcinoma in pleural fluid cytology.

Lymphangioleiomyomatosis in lymph node cytology: Another "Floating Island" to visit.

Lymphangioleiomyomatosis (LAM) is a rare disease with variable presentations. The neoplastic cells in LAM demonstrate a unique and diagnostically important "myomelanocytic" phenotype. Cytologic reports of LAM are infrequent and have not in the past emphasized the floating island pattern in which circumscribed aggregates of lesional cells are rimmed by appliques of flattened endothelium. This case illustrates the cytology of LAM and emphasizes that the floating island cytoarchitectural pattern more classically associated with entities such as hepatocellular carcinomas may be seen in cytological preparations of LAM at unanticipated body sites.

Invasive urothelial carcinoma with squamous differentiation and associated high-risk human papilloma virus infection: Clinical, cytologic, and histologic features of a rare entity.

We correlate the fine needle aspiration (FNA) cytologic findings with the histologic features of an invasive high-grade urothelial carcinoma showing squamous differentiation in the setting of high-risk Human Papilloma Virus (hrHPV) infection. To our knowledge, only extensive urinary bladder catheterization has been associated with hrHPV-positive urothelial carcinoma with squamous differentiation, and rarely at that. Herein, we present a case arising in a patient with only sparse and intermittent catheterization. A 69-year-old woman presented with voiding difficulties, and after continued symptoms, a Foley catheter was placed, and a cystoscopy procedure revealed two 1-2 cm inflammatory masses. Excisional biopsies were interpreted as papillary urothelial carcinoma. One month follow-up pelvic imaging demonstrated a new mass involving the urinary bladder neck, with irregular wall thickening and perivesical fat stranding, as well as probable vaginal involvement. CT-guided FNA (CT-FNA) to collect smears and core biopsies revealed an invasive urothelial carcinoma with squamous differentiation. HPV-cytopathic changes amid squamous metaplasia and dysplasia were noted on FNA smears with HPV E6/E7 RNA in situ hybridization (ISH) showing on the FNA core biopsy specimen. Immunostains showed that the tumor cells were positive for P16 (strong, diffuse), CK7, p63, ER, and GATA3 (patchy). Subsequent radical cystectomy revealed the extent of the patient's carcinoma, with direct extension to the vaginal wall, and involvement of the radial soft tissue resection margins. Describing the cytomorphologic features of a hrHPV positive urothelial carcinoma with squamous differentiation, without an extensive history of urinary catheterization or prior known history of HPV infection, emphasizes the role of cytopathology as a powerful diagnostic tool for recognizing a unique and unexpected lesion.

Accuracy of Preliminary Pathology for Robotic Bronchoscopic Biopsy.

BACKGROUND: Diagnosis and treatment of peripheral pulmonary lesions (PPLs) currently require at least 2 procedures. An all-in-1 approach would require diagnosing malignancy with preliminary cytology results. This study investigated the concordance between preliminary cytology and final pathology results in biopsies of PPLs obtained by shape-sensing robotic-assisted bronchoscopy (ssRAB). METHODS: This study was a retrospective, consecutive, single-arm, single-center study of 110 ssRABs for PPLs. Concordance was defined as agreement between preliminary cytology and final pathology results. Accuracy, sensitivity, specificity, positive and negative predictive values, and safety outcomes were examined. RESULTS: The concordance was 89% for needle biopsies, 85% for forceps biopsies, and 92% overall, with substantial agreement. There was no significant association of concordance with patients' demographics or lesion characteristics. Preliminary cytology resulted in a malignant diagnosis in 70%, a nonmalignant diagnosis in 4%, and a nondiagnostic result in 26%, with accuracy of 86% and sensitivity of 84%. The total complication rate was 3.6%, with a pneumothorax rate of 1.8%. CONCLUSIONS: This study compared the concordance of preliminary pathology results with final pathology results for ssRAB biopsies in PPLs. The results showed that preliminary samples have a high concordance with final pathology results and may enable management of PPLs with a single anesthetic procedure including biopsy, staging, and treatment.

Development and technical validation of an artificial intelligence model for quantitative analysis of histopathologic features of eosinophilic esophagitis.

Background: In an attempt to provide quantitative, reproducible, and standardized analyses in cases of eosinophilic esophagitis (EoE), we have developed an artificial intelligence (AI) digital pathology model for the evaluation of histologic features in the EoE/esophageal eosinophilia spectrum. Here, we describe the development and technical validation of this novel AI tool. Methods: A total of 10 726 objects and 56.2 mm2 of semantic segmentation areas were annotated on whole-slide images, utilizing a cloud-based, deep learning artificial intelligence platform (Aiforia Technologies, Helsinki, Finland). Our training set consisted of 40 carefully selected digitized esophageal biopsy slides which contained the full spectrum of changes typically seen in the setting of esophageal eosinophilia, ranging from normal mucosa to severe abnormalities with regard to each specific features included in our model. A subset of cases was reserved as independent "test sets" in order to assess the validity of the AI model outside the training set. Five specialized experienced gastrointestinal pathologists scored each feature blindly and independently of each other and of AI model results. Results: The performance of the AI model for all cell type features was similar/non-inferior to that of our group of GI pathologists (F1-scores: 94.5-94.8 for AI vs human and 92.6-96.0 for human vs human). Segmentation area features were rated for accuracy using the following scale: 1. "perfect or nearly perfect" (95%-100%, no significant errors), 2. "very good" (80%-95%, only minor errors), 3. "good" (70%-80%, significant errors but still captures the feature well), 4. "insufficient" (less than 70%, significant errors compromising feature recognition). Rating scores for tissue (1.01), spongiosis (1.15), basal layer (1.05), surface layer (1.04), lamina propria (1.15), and collagen (1.11) were in the "very good" to "perfect or nearly perfect" range, while degranulation (2.23) was rated between "good" and "very good". Conclusion: Our newly developed AI-based tool showed an excellent performance (non-inferior to a group of experienced GI pathologists) for the recognition of various histologic features in the EoE/esophageal mucosal eosinophilia spectrum. This tool represents an important step in creating an accurate and reproducible method for semi-automated quantitative analysis to be used in the evaluation of esophageal biopsies in this clinical context.