Background Underrepresented populations, who often have the highest need for accessible healthcare, frequently face barriers to accessing services. To address health inequities, researchers evaluated a community-informed lab-in-a-van model designed to increase access to COVID-19 testing for vulnerable populations. Methods Free saliva-based SARS-CoV-2 diagnostic testing was offered between June 2023 and July 2024 at 123 events in Connecticut, USA using a CLIA-certified mobile laboratory. Approximately 100 local leaders and organizations informed the program design. After providing samples, participants completed an IRB-approved survey; responses were stored using REDCap. Results Offering on-site testing helped remove barriers and increased access for traditionally underserved communities. Overall, 1,428 individuals were tested, and 838 completed a testing experience survey. Of respondents, 54% identified as BIPOC, 59% reported annual household income under $25,000, and 31% were uninsured. Participants reported that the service was easy to access (74%) and comfortable to use (75%); 29% received their first COVID-19 test, and 48% were unaware of alternative testing options. Results were reported in an average of 3.1 hours, enabling many participants to receive diagnostic results during the community event; 48 positive samples were identified. Conclusions This program evaluation demonstrates that community-informed mobile testing programs capable of delivering same-day diagnostic results can expand access to testing among underserved populations and may represent a scalable strategy for improving diagnostic access during future public health emergencies.

Background. Partnering with community leaders, we sought to address ongoing diagnostic testing needs in underserved neighborhoods and evaluate whether a saliva-based mobile testing program could help overcome barriers to testing for uninsured and low-income individuals. This is critical as many lack a primary care provider, cannot access reliable health information, or have limited financial resources. Methods. Free saliva-based, SARS-CoV-2 diagnostic testing was offered at 123 local community events in Connecticut, between June 2023 to July 2024. The SalivaDirect extraction-free RT-qPCR protocol was run on a CLIA licensed van operated by Yale Pathology Labs under FDA Emergency Use Authorization. Testing locations were identified and advertised in partnership with the community. Patient perspectives on approachability, convenience, and usefulness of mobile testing were recorded via REDcap. Results. Approximately 100 local contacts informed the mobile testing model. Overall, 1,428 individuals participated, with 838 completing a testing experience survey. Of these, 54% identified as Black, Indigenous, People of Color; 59% reported annual household income less than $25,000; 31% were uninsured. Test results were reported in an average 3.1 hours, 48 positive samples were identified. Test takers agreed it was easy to access the van (74%) and felt comfortable (75%); 29% received their first COVID-19 test at the van; 48% were unaware of alternate testing; 44% reported difficulty accessing health care; and 49% identified transportation as a challenge. Conclusions. This study demonstrated the positive impact mobile testing could have for overcoming barriers to accessing healthcare, and its potential to serve as a framework for managing and responding to future public health needs. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This mobile testing pilot was supported by the National Institutes of Health (RP2 #R0604) as part of the RADx Underserved Populations (RADx-UP) program. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Yale University Institutaional Review Board APPROVED protocol [IRB Protocol# 2000034551] I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Objectives We investigate the potential role of BRAF testing in guiding surgical intervention in papillary thyroid carcinoma (PTC). Methods Thyroid fine-needle aspiration (FNA) cases with available BRAF result and follow-up thyroidectomy for PTC were included in the study. Cytology and surgical diagnoses were correlated with BRAF status. Results There were 151 cases of thyroid FNA specimens with BRAF testing (70 mutant and 81 wild-type BRAF) and histologically confirmed unilateral, unifocal PTCs. There were no differences in age, sex, tumor size, or lymphovascular invasion on thyroidectomy specimens between mutant and wild-type BRAF cases. BRAF mutation was significantly associated with cytology diagnosis (P < .001), PTC subtype (P < .001), extrathyroidal extension (ETE) (P = .006), and higher tumor (T) stage (P = .04). However, an analysis within the histologic subtypes of PTC revealed no significant association between BRAF mutation and ETE or higher T stage. There was also no difference in central (P = .847) or lateral (p = 1) neck lymph node (LN) metastasis. Conclusions BRAF mutation identified in thyroid FNA specimens correlates with histologic subtypes but is not an independent factor for predicting PTC biological behavior and should not be used to guide the extent of LN dissection.

Background:The initial diagnosis of papillary thyroid carcinoma (PTC) is frequently made via Fine-Needle Aspiration (FNA).FNAs exert physical strain on epithelial clusters and represent a test of cohesion.Some tumors resist the strain and remain in tightly-packed clusters, while others exhibit discohesion, with single cells shedding off of cellular groups.The single cell pattern (SCP) is a correlate of the epithelial-mesenchymal transition (EMT), a concept best described and understood in lobular breast carcinoma and hereditary signet ring cell gastric adenocarcinoma.To our knowledge, no studies have addressed the prognostic significance of the SCP in PTC.Our aim was to correlate SCP in FNAs diagnostic of PTC with aggressive features at the time of resection and with local recurrence free survival.Design: 87 consecutive FNAs diagnostic of PTC ("Suspicious for PTC" or "Positive for PTC") with confirmatory surgical resections were identified and retrieved from the pathology archives.Slides were reviewed and the presence of the SCP was recorded.SCP was defined as single cells readily visible separate from clusters at 4x (Figure 1).Presence of SCP was compared to clincopathologic features gathered from chart review. Results:The SCP was observed in 42/87 (48%) FNAs diagnostic of PTC.Median follow-up of the SCP group was 4.9 years (range 1.2-7.9)and 5.9 years (range 0.4-8.2) in the group without SCP.The average age at FNA was 50.5 years, and the F:M ratio was 4:1.The single cell pattern was associated with a 2.6 times greater rate of lymph node positivity at resection (p=0.04,95% CI 1.1-6.4).However, SCP was not significantly correlated with tumor size or lymphovascular invasion at resection (Table 1).A non-significant trend of local recurrence in the SCP group was noted (Figure 2). . Conclusions:The SCP is readily appreciated in FNAs diagnostic of PTC, and is significantly correlated with LN positivity at resection, and shows a trend of increased local recurrence.SCP may indicate a more aggressive phenotype in PTC.Due to the indolent course of PTC, a larger cohort with longer follow-up will be pursued to further evaluate the significance of the SCP in PTC FNAs.

Background: Cystic fibrosis (CF) is a disease with significant morbidity/mortality that requires lifelong monitoring and treatment.Bronchoalveolar lavage (BAL) is used in CF patients (pts) for microbiology studies; however, literature regarding cytologic findings in BALs from CF pts is sparse.Furthermore, differences between pediatric and adult CF BAL cytology have not been described.Therefore, we sought to delineate cytologic features of BALs from CF pts and to determine whether these parameters differ between pediatric and adult cases.Design: 56 BALs from 48 CF pts (22 from 18 adults, 34 from 30 children) were retrospectively sequentially reviewed.Cytologic features assessed included alveolar macrophage bi/multinucleation, presence of orangeophilic/dyskeratotic bronchial epithelial cells, clustering of macrophages with inflammatory cells +/-bronchial epithelial cells, presence of Creola bodies, degree of acute inflammation, and presence of background mucin and/or debris.Clinical history and microbiology results were obtained from the electronic medical record.Cytologic and clinical parameters were compared between the two groups using Fischer's exact test.Results: Pt ages ranged from 0-77 years (mean=16.3years).Binucleation and clustering were observed in 89.3% and 80.4% of all cases, respectively.Creola bodies were only present in 5.36% of all cases and were not seen in any pediatric BALs.There was a trend toward greater frequency of severe inflammation in adults.Debris/ mucin was more often present in adult cases (58.8% vs 27.3%, p=0.029).Of cases with fungal and mycobacterial (AFB) cultures, 22/50 (44%) were positive for fungi and 7/49 (14.3%) were positive for AFB; AFB growth was more common in adult specimens (30.0%vs 3.45%, p=0.0140). Conclusions:To the best of our knowledge, our study is the first to describe cytologic findings from BALs in CF pts.Macrophage binucleation and cell clustering are common findings in CF BALs; recognition of these as part of the CF cytologic picture can help prevent misinterpretation as malignancy.We observed a trend toward more frequent severe acute inflammation in adult specimens and found that a "dirty" background of mucin/debris is more frequent in adult pts, reflective of the disease's natural progression.Finally, 44% of all cases had positive fungal cultures and nearly 1/3 of adult CF cases grew AFB, suggesting that special stains on CF BAL cytology specimens may be useful in early detection and initiation of antimicrobial treatment.

The Bethesda System for reporting thyroid cytopathology (BSRTC) predicts an incidence of malignancy of less than 5% in thyroid nodules with a benign diagnosis on fine-needle aspiration (FNA). However, recent series have suggested that the true rate of malignancy might be significantly higher in this category of patients. We reviewed our experience by performing a retrospective analysis of patients with benign thyroid FNA results who underwent thyroidectomy between 2008 and 2013 at a large academic center. Information including demographics, ultrasound features, FNA diagnosis, and surgical follow-up information were recorded. Slides were reviewed on cytology-histology discrepant cases, and it was determined whether the discrepancy was due to sampling or interpretation error. A total of 802 FNA cases with a benign diagnosis and surgical follow-up were identified. FNA diagnoses included 738 cases of benign goiter and 64 cases of lymphocytic thyroiditis. On subsequent surgical resection, 144 cases were found to be neoplastic, including 117 malignant cases. False negative, defined as interpretation error and inadequate biopsy of the nodule harboring malignancy, was 6%. When cases of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were excluded from the analysis, false-negative rate was 5%. When microPTC cases were excluded, false-negative rate was 3% and was slightly less than 3% when both microPTC and NIFTP cases were excluded from the analysis. Retrospective review of neoplastic cases showed that 57% were due to sampling error and 43% were due to interpretation error. Interpretation error was more likely to occur in follicular patterned neoplasms (75%), while sampling error was more common in non-follicular variants of papillary thyroid carcinoma (non-FVPTC) (61%). With the exclusion of microPTC, interpretation errors were still more likely to occur in follicular neoplasms (79%) but there was no significant difference in sampling error between non-FVPTC (37%) and follicular patterned neoplasms (42%). Tumor size was larger in cases with interpretation error (mean = 2.3 cm) compared to cases with sampling error (mean = 1.4 cm). This study shows that the false-negative rate of thyroid FNA at our institution is not significantly above the rate suggested by the BSRTC. Interpretation errors were more likely to occur in follicular patterned neoplasms, while non-FVPTC was more frequently found in false negative cases due to inadequate sampling.

Background: In 2016, the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) developed a new set of nomenclature and definitions for histopathology of the ascending aorta.We specifically investigated Marfan Syndrome (MS), Loeys-Dietz Syndrome (LDS) and non-syndromic aortas to see how our understanding of these diseases is impacted by these new criteria.Design: Aortic specimens from patients with MS (n=39), LDS (n=21), and nonsyndromic patients (n=53) were selected from our surgical archives along with basic phenotypic information.Each case was independently scored by 2+ observers in a blinded fashion for 13 features using H&E and Movat stained slides.Disagreements were adjudicated by a cardiovascular pathologist.All data was categorized, converted into numbers, tabulated, and analyzed using a Mann Whitney U test.Results: The average age of resection was lower in both MS (30±14) and LDS (20±16) cases than in non-syndromic cases (63±15), but no differences were noted in the sex/ racial distribution of the groups.The total medial degeneration score was higher in MS cases (2.2±0.8 in a 0-3 scale) than in LDS cases (1.7±1, p=4.4x10 -2 ) or non-syndromic cases (1.7±0.8,p=2.6x10 -3 ).Among patients with MS, the average score for mucoid extracellular matrix accumulation (MEMA) was higher for both extent (3.4±1.7 in a 0-6 scale) and severity (3.2±1.9)than that seen in non-syndromic cases (2.4±1.9 p=3.6x10 -3 and 2.2±1.9 p=3.7x10 -3 ; respectively).The average score was not significantly different in patients from non-syndromic cases or from LDS patients for either extent (2.6±1.8) or severity (2.4±1.8).Average elastic fiber loss was pronounced for both extent and severity in both MS (2.2±0.9 and 2.2±1, respectively; 0-3 scale) and LDS (1.7±1.1 and 1.7±1.2) compared to non-syndromic cases (1.0±1.2 and 0.9±1.1;all p values < 0.02).Conversely, the average extent and severity of smooth muscle cell nuclei loss was greater in non-syndromic cases (1.8±1.0 and 1.4±0.7)compared to MS (0.6±0.9 and 0.6±0.8)and LDS (0.5±0.9 and 0.3±0.6;all p values <10 -4 ).Conclusions: This is the first evaluation of the new AECVP/SCVP aorta nomenclature and definitions in MS and LDS aortas.We clearly demonstrate that, in general, MS has more significant medial degeneration at the time of surgery compared to LDS or non-syndromic cases.There is also significantly more elastic fiber loss and less smooth muscle cell loss in these syndromic diseases compared to non-syndromic diseases.

Background: In 2016, the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) developed a new set of nomenclature and definitions for histopathology of the ascending aorta.We specifically investigated Marfan Syndrome (MS), Loeys-Dietz Syndrome (LDS) and non-syndromic aortas to see how our understanding of these diseases is impacted by these new criteria.Design: Aortic specimens from patients with MS (n=39), LDS (n=21), and nonsyndromic patients (n=53) were selected from our surgical archives along with basic phenotypic information.Each case was independently scored by 2+ observers in a blinded fashion for 13 features using H&E and Movat stained slides.Disagreements were adjudicated by a cardiovascular pathologist.All data was categorized, converted into numbers, tabulated, and analyzed using a Mann Whitney U test.Results: The average age of resection was lower in both MS (30±14) and LDS (20±16) cases than in non-syndromic cases (63±15), but no differences were noted in the sex/ racial distribution of the groups.The total medial degeneration score was higher in MS cases (2.2±0.8 in a 0-3 scale) than in LDS cases (1.7±1, p=4.4x10 -2 ) or non-syndromic cases (1.7±0.8,p=2.6x10 -3 ).Among patients with MS, the average score for mucoid extracellular matrix accumulation (MEMA) was higher for both extent (3.4±1.7 in a 0-6 scale) and severity (3.2±1.9)than that seen in non-syndromic cases (2.4±1.9 p=3.6x10 -3 and 2.2±1.9 p=3.7x10 -3 ; respectively).The average score was not significantly different in patients from non-syndromic cases or from LDS patients for either extent (2.6±1.8) or severity (2.4±1.8).Average elastic fiber loss was pronounced for both extent and severity in both MS (2.2±0.9 and 2.2±1, respectively; 0-3 scale) and LDS (1.7±1.1 and 1.7±1.2) compared to non-syndromic cases (1.0±1.2 and 0.9±1.1;all p values < 0.02).Conversely, the average extent and severity of smooth muscle cell nuclei loss was greater in non-syndromic cases (1.8±1.0 and 1.4±0.7)compared to MS (0.6±0.9 and 0.6±0.8)and LDS (0.5±0.9 and 0.3±0.6;all p values <10 -4 ).Conclusions: This is the first evaluation of the new AECVP/SCVP aorta nomenclature and definitions in MS and LDS aortas.We clearly demonstrate that, in general, MS has more significant medial degeneration at the time of surgery compared to LDS or non-syndromic cases.There is also significantly more elastic fiber loss and less smooth muscle cell loss in these syndromic diseases compared to non-syndromic diseases.

CONTEXT:All Food and Drug Administration-approved methods in the United States for human papillomavirus testing including the Hybrid Capture 2 human papillomavirus assay and the Roche cobas human papillomavirus test are approved for cytology specimens collected into ThinPrep media but not for specimens collected into SurePath solution.OBJECTIVE:To compare the performance of the Roche cobas and Hybrid Capture 2 tests for the detection of high-risk human papillomavirus using both ThinPrep and SurePath preparations as part of a validation study.DESIGN:One thousand three hundred seventy-one liquid-based cytology samples, including 1122 SurePath and 249 ThinPrep specimens, were tested for high-risk human papillomavirus DNA using the Roche cobas human papillomavirus test and the Hybrid Capture 2 human papillomavirus assay. For cases with discrepant results, confirmatory testing was performed using Linear Array human papillomavirus testing.RESULTS:One hundred and fifty-six (11.38%) and 184 (13.42%) of the 1371 specimens tested positive for high-risk human papillomavirus DNA using the Hybrid Capture 2 human papillomavirus assay and Roche cobas human papillomavirus assay, respectively. In addition, 1289 (94.0%) of 1371 specimens demonstrated concordant high-risk human papillomavirus results with a κ value of 0.72 (95% confidence interval, 065-0.78). There was no statistically significant difference in the percentage of positive high-risk human papillomavirus results between the 2 liquid-based preparations with either assay. Discordant results between the 2 assays were noted in 82 of 1371 cases (6%). Twenty-seven of 82 cases (32.9%) were Hybrid Capture 2 positive/Roche cobas negative and 55 of 82 cases (67.1%) were Roche cobas positive/Hybrid Capture 2 negative. Two of 20 Hybrid Capture 2-positive/Roche cobas-negative cases (10%) and 26 of 37 Roche cobas-positive/Hybrid Capture 2-negative cases (70%) tested positive for high-risk human papillomavirus by Linear Array.CONCLUSIONS:Both assays showed good agreement and excellent specificity with either ThinPrep or SurePath preparations. The number of discordant results was relatively small. The performance of both assays was similar for ThinPrep specimens, but the Roche cobas test demonstrated higher sensitivity with SurePath specimens.

Introduction: The majority of the commercially available methods for testing of high-risk human papillomavirus (hr-HPV) were approved by the Food and Drug Administration (FDA) for ThinPrep (TP) but not SurePath (SP) preparations. Recently, questions about the validity of these hr-HPV testing methods have been raised with SurePath. The objective of the current study is to compare the rates of hr-HPV positivity for different diagnostic categories using the Hybrid Capture II (HC II) (Qiagen, Gaitherburg, MD) method and the Roche Cobas 4800 (Cobas) (Roche, Pleasanton, CA) system for both TP and SP preparations. Materials and Methods: A computerized search was performed to retrieve all patients who received a liquid based (LB) Pap test with hr-HPV testing between September and December 2011 and between September and December 2012. HC II and Cobas methods were used for hr-HPV testing during 2011 and 2012, respectively. The Z-test was used for statistical analysis between the hr-HPV rates among various diagnostic categories between the two LB preparations. Results: 28,515 liquid based Pap tests, including 19% TP, were processed September through December 2011; 32% of which were tested for hrHPV. 27,769 liquid based Pap tests, including 24% TP, were processed September through December 2012; 35% of these were tested for hrHPV. The tables below summarize the rate of hr-HPV positivity for each diagnostic category: comparing two test methods and two preparations (Table 1) and comparing different age groups with two preparations (Table 2). Conclusions: Rates of hr-HPV positivity for cases with ASC-US and LSIL were significantly higher with SP than with TP preparation, regardless of the testing method. In addition, the rates of hr-HPV positivity in patients with ASC-US using Cobas with either TP or SP preparation were comparable to that observed in the ATHENA study. Our data validate the clinical use of Cobas with SP preparation. 81

Various ultrasonographic characteristics of thyroid nodules have been associated with a higher likelihood of malignancy, and certain clinical features may also increase the likelihood of malignancy in patients. This study is designed to determine the ultrasonographic and clinical predictors of malignancy in the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category. A search through the cytology files at our institution was made for cases with diagnosis of AUS/FLUS. The clinical and radiologic findings were correlated with the final surgical pathology diagnosis. A total of 140 cases of AUS/FLUS with corresponding surgical intervention were identified (112 females and 28 males). There was a 79 % malignancy rate in nodules with irregular contours, compared to 51 % in nodules with regular outlines. Nodules demonstrating calcifications showed a 57 % malignancy rate, compared to 50 % in nodules without calcifications. Sixty-one percent of cases with an ultrasonographic diagnosis of indeterminate to suspicious were malignant following surgical resection. The rates of malignancy in patients with radiation exposure, symptomatic nodules, and positive family history of thyroid cancer were 22, 59, and 33 %, respectively. BRAF mutation was demonstrated in 57 % of malignant cases and in none of benign cases. No single clinical or ultrasonographic feature or combination of features is adequately sensitive or specific to identify all malignant nodules. However, a combination of solid nodules, nodules with irregular contours, symptomatic nodules, and positive BRAF mutation has high predictive value for malignancy in patients with a cytologic diagnosis of AUS/FLUS.