This study examines the cost of completing laboratory education programs across degree levels and evaluates the availability and use of financial resources for laboratory students. Its findings support advocacy to reduce student debt, inform federal and state policy, and help institutions strengthen recruitment and retention by addressing financial barriers. This national cross-sectional study surveyed laboratory professionals, educators, and current or recent students across the United States and its territories. It was conducted in a collaboration among the American Society for Clinical Pathology's (ASCP's) Institute for Science, Technology, and Policy; the ASCP Evaluation, Measurement, and Assessment Department; and the ASCP Board of Certification. The cost of attending a laboratory education program generally falls at or below the lower end of national averages for educational expenses among students and working laboratory professionals. Respondents most often rely on self-funding, federal student loans, and private loans, with financing methods varying by enrollment period. Logistic regression showed that dependence on federal loans and younger age were the strongest predictors of student loan participation among laboratory professionals. Continued advocacy is essential to ensure that laboratory professionals remain included in federal and state scholarships, grants, and loan forgiveness programs. As policies governing educational funding evolve, it is increasingly important to engage stakeholders in championing financial support for laboratory professionals. Doing so will help reduce the burden of educational costs and strengthen pathways into laboratory careers, ultimately securing recruitment and retention.
To analyze the clinical heterogeneity of cutaneous manifestations in systemic lupus erythematosus (SLE) and the features of coexisting dermatologic conditions in these patients. The single-center cross-sectional study included 210 patients with SLE followed at Nasonova Research Institute of Rheumatology. Clinical, laboratory, and instrumental parameters were assessed, including disease activity (SLEDAI-2K [Systemic Lupus Erythematosus Disease Activity Index 2000], SLE-DAS [Systemic Lupus Erythematosus Disease Activity Score]), organ damage (Damage Index of SLICC/ACR [Systemic Lupus International Collaborating Clinics / American College of Rheumatology]), and cutaneous manifestations using the CLASI (Cutaneous Lupus Disease Area and Severity Index), R-CLASI (Revised Cutaneous Lupus Erythematosus Disease Areas and Severity Index), and the mucocutaneous domain of Easy-BILAG (Easy British Isles Lupus Assessment Group). Coexisting dermatologic conditions and skin changes not directly related to SLE activity were additionally analyzed. Cutaneous and mucosal involvement was observed in 85% of patients during the disease course and represented one of the most frequent manifestations at SLE onset. At study inclusion, active mucocutaneous manifestations were present in 50% of patients. Cutaneous involvement was characterized by marked clinical heterogeneity and a high prevalence of overlapping phenotypes, including acute and chronic cutaneous lupus, mucosal lesions, and non-scarring alopecia. Active cutaneous involvement was associated with serositis and hemolytic anemia. Coexisting dermatologic conditions, including treatment-related skin complications, were identified in 70% of patients. Cutaneous and mucosal manifestations in SLE constitute a complex, multicomponent disease phenotype reflecting both systemic inflammatory activity and processes of chronicity and damage accumulation. The high prevalence of overlapping cutaneous phenotypes and coexisting dermatologic conditions underscores the need for comprehensive skin assessment and a multidisciplinary approach to the management of patients with SLE. Цель. Проанализировать клиническое разнообразие кожных проявлений системной красной волчанки (СКВ) и их сочетание с сопутствующей дерматологической патологией. Материалы и методы. В одноцентровое одномоментное исследование включены 210 пациентов с СКВ, наблюдавшихся в ФГБНУ «НИИР им. В.А. Насоновой». Оценивали клинические, лабораторные и инструментальные показатели, активность заболевания (SLEDAI-2K [Systemic Lupus Erythematosus Disease Activity Index 2000] – индекс активности СКВ в модификации 2000 г., SLE-DAS [Systemic Lupus Erythematosus Disease Activity Score] – счет активности СКВ), органное повреждение (индекс повреждения Международной группы сотрудничающих клиник по системной красной волчанке / Американской коллегии ревматологов [Systemic Lupus International Collaborating Clinics / American College of Rheumatology – SLICC/ACR]), кожные проявления с использованием индексов CLASI (Cutaneous Lupus Disease Area and Severity Index – индекс площади и тяжести кожной волчанки), R-CLASI (Revised Cutaneous Lupus Erythematosus Disease Areas and Severity Index – модифицированный индекс площади и тяжести кожной волчанки) и кожно-слизистого домена Easy-BILAG (Easy British Isles Lupus Assessment Group – облегченная группа оценки волчанки на Британских островах). Дополнительно анализировали сопутствующие дерматологические заболевания и кожные изменения, не связанные напрямую с активностью СКВ. Результаты. Поражение кожи и слизистых оболочек выявлено у 85% пациентов за период заболевания, что являлось одним из частых проявлений дебюта СКВ. У 50% пациентов на момент включения обнаружена активная кожно-слизистая симптоматика. Кожные проявления характеризовались выраженной гетерогенностью и высокой частотой сочетанных фенотипов, включая острые и хронические формы кожной волчанки, поражение слизистых оболочек и нерубцовую алопецию. Активное кожное поражение ассоциировалось с серозитом и гемолитической анемией. У 70% пациентов выявлена сопутствующая дерматологическая патология, включая кожные осложнения терапии. Заключение. Кожные и слизистые проявления СКВ формируют сложный, многокомпонентный фенотип заболевания, отражающий как активность системного воспаления, так и процессы хронизации, накопления повреждения. Высокая частота сочетанных форм кожной волчанки и сопутствующей дерматологической патологии подчеркивает необходимость комплексной оценки кожного синдрома и междисциплинарного подхода к ведению таких пациентов.
Until recently, due to the absence of standardized guidelines tailored for veterinary use, the evaluation of genetic variant pathogenicity for single-gene diseases was based on a personal interpretation of the presented evidence, which has led to inconsistencies. With the publication of the animal variant classification guidelines (AVCG), a more objective approach became available. Variants are evaluated by the International Society of Animal Genetics (ISAG)-endorsed Variant Pathogenicity Working Group (VPWG) based on 23 criteria and are subsequently labeled as pathogenic, likely pathogenic, variant of uncertain significance, likely benign or benign. While the accuracy was thoroughly tested in the original publication, the reproducibility of the various steps involved was only briefly checked, which is why the current analysis was performed. Each variant from a set of 150 published likely causal variants for single-gene diseases from three species (dog, cat, horse) was independently and blindly assessed by three different VPWG reviewers, each applying the same AVCG. An overall agreement of 93% for decisions on the scope, that is, whether they fit the inclusion criteria to allow evaluation with AVCG, was found. More importantly, the reproducibility of pathogenicity label assignment was 65% and the reproducibility of clinical relevance was 83%. The reproducibility of AVCG-pathogenicity classification is in line with reports using the human American College for Medical Genetics and Genomics and Association for Molecular Pathology guidelines for human variants. Overall, the reproducibility of the AVCG classifications as used by the ISAG-endorsed VPWG supports the utility of these classifications in veterinary species.
Rhino-sino-orbital mucormycosis (RSOM) is a life-threatening, emergent medical and surgical condition with high mortality. Although direct intraorbital delivery methods of amphotericin B have been explored, clear guidelines for its administration and dosing are lacking. We conducted this prospective study to determine the role of intraorbital amphotericin B (IOAB) in the management of advanced RSOM and assessed histologic changes in response to IOAB administration. Patients with advanced orbital disease were offered treatment with IOAB before exenteration. Individuals who refused IOAB and underwent orbital exenteration made up a control group. Hematoxylin-eosin-stained slides of orbital exenterations were reviewed and representative whole slide images were captured. Areas of necrosis, inflammatory cell infiltrate, and fibrosis were annotated as indicators of tissue inflammatory response, quantified and estimated as a percentage of the total area of the tissue. A semiquantitative assessment of fungal load was conducted. The control group (n = 9) showed statistically significantly greater mean area (P = .004) and percentage area (P = .002) of tissue destruction, angioinvasion (P = .02), and optic nerve invasion (57% vs 33%; P = .31) compared with the intervention group (n = 9). Fungal load was low in test cases but high in most of the control group (P = .15). Inflammation of ocular structures was absent in 5 test cases but present in all control group cases (P = .008). The considerably lower tissue destruction, fungal load, angioinvasion, and invasion of the optic nerve in orbital exenteration specimens following administration of IOAB indicates a promising role in the treatment of patients with RSOM and advanced involvement of the orbit.
To determine the prevalence of cerebral atrophy in a multi-ethnic systemic lupus erythematosus (SLE) cohort and to identify its associated clinical factors. In this cross-sectional study (2024-2025), adults fulfilling the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE at University Malaya Medical Centre were recruited. Demographic, clinical, serological, vascular and treatment data were collected. Disease activity and cumulative damage were assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Non-contrast CT brain scans were performed with cerebral atrophy graded using the validated Global Cortical Atrophy (GCA) score. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). Fisher's exact test and χ2 test were used to test the association between two categorical variables where appropriate, while group differences were tested using the Mann-Whitney U test. Univariable and multivariable logistic regression analyses were considered to identify variables that were significantly associated with cerebral atrophy. Seventy patients (92.9% female; median age 40 (IQR 31.75-50.25) years; median disease duration 12 (IQR 4-19) years were included. Cerebral atrophy was present in 52.9%, predominantly mild (75.7%). From univariate comparisons, patients with cerebral atrophy were significantly older in age, had longer disease duration, lower education, higher SDI and poorer MoCA scores. Multivariable analysis showed that older age (OR 1.10 per year, 95% CI 1.04 to 1.18) and neuropsychiatric SLE (NPSLE) (OR 4.58, 95% CI 1.05 to 24.07) contributed to increased odds of cerebral atrophy, while higher educational attainment was linked with reduced odds of cerebral atrophy (OR 0.22, 95% CI 0.06 to 1.03). Cerebral atrophy is common in SLE and independently associated with age, education, NPSLE and cognitive impairment, reflecting neuroinflammatory and neurodegenerative mechanisms. These findings underscore the importance of cognitive screening and targeted monitoring of high-risk patients.
In a previous study, we reported that using a first-tier quantitative Lyme serologic index may obviate the need for second-tier confirmatory testing in samples above a defined cutoff value. Here we have expanded on the sample size to confirm and better refine the potential utility of the serologic index to aid in timely clinical decision-making. We reviewed 1 year of Lyme serologic test results sent to our laboratory for testing using a modified 2-tier testing algorithm (MTTT) to determine the probability of second-tier confirmation based on the initial Lyme index value. Using the original Lyme index cutoff at which 100% of samples confirmed on second-tier testing (2.68), in the expanded dataset, 98.7% of samples confirmed at this cutoff. Using all of the expanded sample set data, we defined 6 Lyme index brackets from highly positive to equivocal to estimate the probability of the first-tier test confirming on second-tier testing. We also constructed a formula relating the index to the probability of confirmation across the continuum of index values to predict second-tier confirmation in an MTTT algorithm. The use of a Lyme test index value may eliminate the need for confirmatory testing on many positive first-tier samples in patients suspected of having Lyme disease. First-tier Lyme test results may be improved by reporting the index value along with the probability of confirmation. This may facilitate more timely diagnosis and clinical decision-making and potentially improve the time to antimicrobial therapy.
While recent studies have estimated the carbon footprint of surgical pathology, they did not consider the many other impacts this activity has on the environment. We aimed to estimate the environmental impacts of the preparation of hematoxylin-phloxine-saffron (HPS) staining, Congo red (CR) staining, and immunofluorescence (IF) staining for a biopsy analysis. We used a comprehensive life cycle assessment methodology of 18 environmental indicators. Life cycle assessment is a standardized and robust method for comprehensively assessing the various environmental impacts of a process throughout its entire life cycle. All contributing items (eg, materials, reagents, electricity) within the different technical steps in the surgical pathology department were considered. For the entire procedure (HPS + CR + IF), the electricity consumption of the cryostat for IF staining was the main contributing item for all indicators (from 19.4%-75.8%), except land use. The other most impactful contributing items were (1) single-use materials used during specimen grossing (second or third largest contributing item for 8 indicators), (2) electricity consumption during slide/block storage (second largest contributor for 6 indicators), (3) materials and consumables used during sample receipt (third largest contributor for 6 indicators), (4) materials used during cryostat section (third largest contributor for 6 indicators), and (5) reagents used during IF staining (second or third largest contributor for 5 indicators). Interestingly, for formalin fixation, the main environmental impacts were represented by global warming, fine particle matter formation, and human toxicity. These data allow us to better understand the environmental impacts of our activities and to propose more pertinent eco-design solutions.
We sought to improve test utilization for 8 autoimmune antibody panels. Three interventions (test ordering guidance, clinical pathway guidance, and duplicate test blocking) were implemented at 6-month intervals. Over 3 years, we recorded trends in test volumes, duplicate tests, and positive results. We conducted chart reviews for two 3-month periods 1 year apart to assess the impact on patient Antibody Prevalence in Epilepsy and Encephalopathy (APE2) scores. Comparing the first 6 months with the last 6 months of the 3-year study, we observed a 36.5% decrease in overall test volume and a 95.5% reduction in duplicate tests. The final true-positive rate based on clinical diagnosis was low, however, at only 1.6% (40/2550) of tests performed and 1.3% (24/1883) of patients tested. Performance did not improve over the study period. Chart reviews (n = 194) showed only 8 of 106 (7.5%) patients had an APE2 score of at least 4 in January through March 2023, and 12 of 88 (13.6%) met this threshold in January through March 2024. Two of 20 total patients with an APE2 score of at least 4 had a new diagnosis of autoimmune central nervous system disease compared with 0 of 174 patients with a score below 4 (P < .001), affirming the predictive value of the scorecard. Although reductions in test volume and duplicate testing were observed, clinicians continued to order a substantial number of tests for patients whose clinical picture was not suggestive of autoimmune epilepsy or encephalopathy. Although there was some improvement in appropriate ordering when assessed by retrospective APE2 scores, this value did not reach statistical significance.
Despite the availability of different cell block preparation techniques in the literature, there is an unmet need for a technique that meets the needs of a low-tech, low-resource laboratory for diagnostic and ancillary testing. We aimed to develop and validate a modified method of cell block preparation in terms of its efficacy in cellular preservation and its utility in ancillary testing. Cell blocks were prepared using fresh patient plasma and activated partial thromboplastin time-ellagic acid reagent. A prospective study was conducted to assess the performance of this modified plasma-based cell block in terms of (1) cell yield as well as morphologic and architectural preservation and (2) utility of the modified plasma-based cell block in immunohistochemistry in terms of preservation of antigenicity, staining quality, and the presence of background interference. Special stains and molecular testing were performed in select cases. Of the 64 samples we included, 59 met the inclusion criteria. Diagnostic concordance between cell block and smear was 92.6% in body fluids and 43.75% in fine needle aspiration cytologic aspirates. Among fluid sediment modified plasma-based cell blocks, 92.5% were representative, with minimal degeneration and excellent architecture, whereas fine needle aspiration cytologic modified plasma-based cell blocks showed representative material in 75.0%, minimal to moderate degeneration in 81.25%, and excellent architectural preservation in 58.3% of blocks. Immunohistochemistry performed in 9 cases showed strong staining in 90.0% and good clarity in 86.9% of cases, with no background staining. Special stains and selective molecular tests were successfully performed. Modified plasma-based cell block testing improves diagnostic yield and preserves morphology. Compatible with a broad spectrum of ancillary testing, chiefly immunohistochemistry and commonly used molecular tests, it is a feasible and cost-effective alternative.
In healthy individuals, CD34+ stem cells are detectable in peripheral blood in relatively low and stable numbers. The clinical utility of peripheral blood CD34+ stem cell quantitation in the evaluation of pancytopenia has not been systematically studied. We used a large archival clinical cohort (n = 154) of pediatric patients from our pediatric-only institution without a history of hematologic disorder or circulating blasts on morphology who underwent peripheral blood flow cytometric screening for any reason. Circulating CD34+ stem cells and total progenitors were quantified and correlated with clinical characteristics and outcomes. Patients ultimately diagnosed with aplastic anemia (n = 15) showed significantly decreased circulating progenitors compared with those with cytopenias of alternative causes, whereas patients with infectious, inflammatory, or other presumed reactive conditions often demonstrated larger CD34+ progenitor populations, consistent with preserved or responsive marrow function. Using receiver operating characteristic analysis, the optimal cutoff for %CD34+ progenitors was 0.0124%, which was rounded to 0.01% for clinical interpretability. These findings support the potential clinical utility of peripheral blood CD34+ quantitation in the diagnostic workup of pediatric pancytopenia.
Timely access to pathology reports has increased the need for clear patient-facing explanations. We evaluated whether large language model (LLM)-generated responses to pathology report questions from patients are comparable in quality to explanations written by pathologists and assessed how LLM configuration influences performance. Sixty-five anonymized real-world patient questions from an online pathology education platform were answered using 5 LLM configurations varying by model architecture, prompting strategy, and retrieval-augmented generation. Responses were evaluated using a structured rubric that assessed accuracy, relevance, clarity, empathy, and safety; they were compared using pairwise arena testing with Bradley-Terry modeling to rank performance. Across rubric domains, LLM responses demonstrated performance comparable to pathologist explanations, with 1 configuration meeting noninferiority criteria. Pairwise arena comparisons indicated that the configuration parameters strongly influenced performance, with both model size and retrieval augmentation associated with improved response preference. The highest-performing configuration combined a larger model with retrieval from a curated pathology knowledge base and was strongly preferred over pathologist-written responses. Carefully configured LLM systems can generate patient-facing explanations of pathology reports comparable in quality to pathologist-written explanations. Prompting strategy, model size, and retrieval integration were associated with performance differences, underscoring the importance of system configuration in developing LLM-based tools to expand access to understandable pathology information.
To report and describe a first case of primary Paget-like intraepithelial glandular lesion of the bronchus in an 83-year-old White man undergoing a right lower lobe segmentectomy for a primary squamous cell carcinoma (SCC). The focus of the bronchial primary Paget-like intraepithelial glandular lesion was discovered incidentally, and the diagnosis was confirmed by detailed histologic examination, immunohistochemical studies, and targeted genetic sequencing. Detailed review of clinical history and pertinent radiology was also undertaken to exclude metastasis from another site. Atypical glandular cells were identified within the epithelium of a subsegmental bronchus examined, at a distance from the primary SCC. The lesional cells were positive for CK7, GATA3, m-CEA, and mucicarmine; were weakly positive for ER and PR; and showed 2+ membrane staining for HER2. They were cytologically different from the SCC and negative for p40 and CK5/6. There was no history of breast carcinoma and no suspicious lesions within mammary tissue on preoperative imaging. The patient has no evidence of recurrence or new intra- or extrathoracic lesions at 18 months postsurgery. We report the first case of primary Paget-like intraepithelial glandular neoplasia originating in the bronchial epithelium. While the clinical significance of this unusual finding is unknown, it challenges the existing hypotheses concerning the cellular origin of extramammary Paget disease, which include Toker cells, pluripotent keratinocyte stem cells, and apocrine gland ducts, none of which are native to the bronchial epithelium.
The adaptation of clade 2.3.4.4b influenza A(H5N1) to dozens of mammalian species, including dairy cattle, raises concerns about potential spillover into humans. If the virus develops human-to-human transmissibility, sensitive diagnostics will be critical to containment efforts. We sought to determine the lower limit of detection of commercial influenza A tests for the circulating bovine-adapted strain of H5N1. We determined the 95% lower limit of detection (LLOD) of 4 commercial respiratory virus panels for detecting inactivated bovine H5N1 (A/bovine/Ohio/B24OSU-439/2024). Two of the tested panels provide seasonal influenza A subtyping, the BioFire Respiratory Panel 2.1 (BioFire Diagnostics/BioMérieux) and the cobas eplex respiratory pathogen panel 2 (Roche Diagnostics), while 2 panels provide pan-influenza A detection, the Xpert Xpress CoV-2/Flu/RSV plus (Cepheid), and the Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (Hologic, Inc). Serial dilutions of H5 RNA (400-25 copies/mL) were prepared in respiratory virus-negative nasopharyngeal swab matrix, and 20 replicates were tested at each concentration. The 95% LLOD for each test was calculated using probit regression. All 4 tests detected H5 with 95% LLODs below 1000 H5 RNA copies/mL. Xpert demonstrated the highest analytical sensitivity (50 copies/mL; 95% CI, 39-160), followed by BioFire (297 copies/mL; 95% CI, 196-3955), Panther Fusion (531 copies/mL; 95% CI, 421-792), and eplex (883 copies/mL; 95% CI, 588-2741). Existing commercial respiratory virus panels can effectively detect bovine H5N1. These platforms could support screening in the event of an H5N1 outbreak, followed by confirmation with specific H5 subtyping, as needed.
Urine organic acid analysis is essential for diagnosing inborn errors of metabolism and is conventionally performed using multistep, labor-intensive sample preparation and gas chromatography-mass spectrometry (GC-MS). We sought to develop and validate a quantitative ultra-performance liquid chromatography quadrupole time-of-flight (UPLC-QTOF) method with a "dilute-and-shoot" approach. 20 µL of calibrator, quality control material, or urine specimen, normalized by creatinine concentration, was mixed with mobile phase A (0.05% formic acid in water) and internal standards to a final volume of 440 µL. The supernatant was injected onto a Waters ACUITY Premier HSS T3 UPLC column, with data acquired in MSE mode on a Waters Xevo G3 QTOF mass spectrometer and quantification achieved using both linear and quadratic regressions. The method quantifies 27 analytes and separates diagnostically important isomers in 20 minutes. Repeatability and reproducibility were 12% or less coefficient of variation, with no carryover observed. Spike-recovery studies demonstrated recoveries between 85% and 115%, and concordant results were obtained from 51 urine specimens vs the conventional GC-MS method. No matrix effect was identified except for 3-hydroxyglutaric acid. Compared with other UPLC-QTOF methods, improved chromatographic performance was achieved with the Premier HSS T3 column, while MSE high-resolution MS data provided fragmentation information to support higher-confidence compound identification. Compared with conventional GC-MS methods, this method requires substantially lower specimen volume and simplified sample preparation. This UPLC-QTOF dilute-and-shoot urine organic acid method demonstrated acceptable analytical and clinical performance. Continued optimization will be pursued to expand the panel and support the diagnosis of a broader range of inborn errors of metabolism.
Autoimmune gastritis (AIG) is characterized by well-described histologic features, yet diagnostic thresholds and reporting practices vary in routine pathology practice. This study aimed to characterize variability in evaluation, ancillary testing, and reporting of AIG across diverse pathology practice settings and training backgrounds. We conducted a national, anonymized, cross-sectional online survey for practicing pathologists who routinely sign out gastric biopsies. The survey assessed diagnostic criteria for AIG, use of ancillary studies, reporting practices, and approaches to overlapping Helicobacter pylori gastritis. Associations between respondent characteristics and diagnostic behaviors were evaluated using χ2 tests and multivariable logistic regression. A total of 163 pathologists completed the survey. Diagnostic thresholds for AIG varied widely, ranging from strict criteria requiring oxyntic gland atrophy, intestinal metaplasia, and enterochromaffin-like-cell hyperplasia to broader approaches recognizing atrophy alone. Only 22% of respondents reported AIG in the main report, while 43% reported in the comments and only one-third routinely subtyped intestinal metaplasia. In all, 52% of respondents routinely ordered gastrin immunohistochemistry in random gastric biopsies. Academic settings were associated with greater reporting detail, while gastrointestinal pathology fellowship training was associated with the use of qualifying terminology such as "early" or "suspicious" AIG (P = .01). Approaches to cases with concurrent H pylori gastritis and oxyntic gland atrophy also showed substantial variability. Diagnostic evaluation and reporting of AIG remain highly variable and are associated with subspecialty training, practice environment, and years of experience. These findings highlight the need for consensus-based guidance to improve consistency, communication, and clinical integration of AIG diagnoses.
This study aims to systematically evaluate the predictive value of platelet parameters (PLT, PDW, MPV, PCT) before initial 131I therapy in patients with differentiated thyroid cancer. This retrospective study included 365 patients with differentiated thyroid cancer (DTC) who underwent initial 131I therapy at the Department of Nuclear Medicine in a tertiary hospital. Treatment response was assessed according to the 2025 American Thyroid Association Guidelines for the Management of Adult Differentiated Thyroid Cancer, and was categorized as Excellent Response (ER) or Non-Excellent Response (non-ER). Univariate and multivariate analyses were performed to examine the association between PLT, PDW, MPV, and PCT with non-ER, adjusting for confounding factors. Results are presented as odds ratios (OR) and 95% confidence intervals (CI). The stability of the results was verified through interaction tests and subgroup analyses. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to assess the predictive value of platelet indices for treatment response. After adjusting for confounding factors, MPV was independently and negatively associated with non-ER (OR = 0.40, 95% CI 0.28-0.58). Interaction analysis suggested that age and ps-Tg influence the association between MPV and non-ER (P = 0.042 and P = 0.031). The ROC curve showed that MPV had a moderate predictive value for non-ER (AUC = 0.664). Based on the maximum Youden index, the optimal cutoff value was determined to be 9.95 fL, with a sensitivity of 0.595 and a specificity of 0.657. MPV demonstrated moderate predictive value in forecasting the response of DTC patients to initial 131I therapy (AUC = 0.664). In clinical practice, MPV may be of adjunctive value in helping to identify patients with poor treatment response at an early stage. However, it is insufficient to be used as the sole basis for clinical decision-making.
The aim of this study was to evaluate the clinical, ultrasonographic, and elastographic parameters in the risk stratification of malignancy for thyroid nodules with indeterminate cytology according to The Bethesda System for Reporting Thyroid Cytology. This retrospective, single-center study analyzed 838 thyroid nodules from 716 consecutive patients for six years. The diagnostic performance of nodule size, Doppler ultrasonography features, American Thyroid Association risk of malignancy guidelines, and Tsukuba elasticity scores via strain elastography was assessed. A multinomial logistic regression analysis was employed to compare indeterminate categories (III, IV, and V) with benign cytology (II) to identify independent predictors of malignancy. Indeterminate nodules exhibited larger mean diameters compared to benign ones (20.83±9.89 vs. 18.65±9.08 mm; p<0.05), and significant associations were identified between III, IV, and V categories and increased peripheral/central vascularization, higher-risk American Thyroid Association risk of malignancy classifications, and elevated Tsukuba elasticity scores (4 and 5). Histopathological malignancy rates were higher in indeterminate groups (p<0.05), whereas patient age and nodule location demonstrated no significant predictive value. Integrated assessment of nodule size, Doppler vascularity, American Thyroid Association risk stratification, and strain elastography significantly enhances the predictive accuracy for malignancy in nodules with indeterminate cytology. These multiparametric indices provide essential guidance for optimizing surgical indications and clinical management in cases of diagnostic uncertainty.
To investigate the expression patterns of ERG, PTEN, and c-Myc proteins in prostate adenocarcinoma; analyze the status of the MYC gene; and evaluate their correlations with clinicopathologic parameters and patient prognosis. In this retrospective study, 152 prostate adenocarcinoma cases were analyzed. Immunohistochemistry was performed for ERG, PTEN, and c-Myc protein expression. Fluorescence in situ hybridization was used to assess ERG rearrangement, MYC gene breakage, and amplification. Statistical analyses were conducted to evaluate associations between molecular markers and clinicopathologic variables, as well as their impact on survival outcomes. The positive expression rates for ERG, PTEN, and c-Myc high expression (immunoreactive score ≥5) were 9.9%, 86.8%, and 50%, respectively. The detection rate of MYC gene amplification was 27.6%. Both c-Myc high expression and MYC gene amplification were significantly associated with the high-grade group (defined as Grade Group ≥3 and/or with cribriform pattern), lymphovascular invasion, advanced T stage, metastasis, and poor prognosis, with gene amplification demonstrating higher prognostic specificity. ERG protein expression was significantly correlated with PTEN positivity, whereas no significant association was found between MYC gene amplification and ERG protein expression; only a nonsignificant mutually exclusive trend was observed. c-Myc activation, particularly MYC gene amplification, is a key driver and specific biomarker for an aggressive phenotype and poor prognosis in prostate adenocarcinoma. Combined detection of ERG, PTEN, and c-Myc status contributes to refining risk stratification systems. The lack of significant association between MYC amplification and ERG expression suggests they may represent distinct oncogenic pathways, warranting further validation in large prospective studies.
Surface low-grade papillary urothelial carcinoma with an invasive phenotype represents an understudied entity with its clinical behavior, therapeutic responses, and long-term outcomes remaining poorly defined. We evaluated 17 patients from a single institution with histologically confirmed surface low-grade papillary urothelial carcinoma with an invasive phenotype, followed by longitudinal clinicopathologic analysis to delineate disease trajectories and treatment outcomes. Surface components of all tumors in this cohort demonstrated a low-grade papillary urothelial carcinoma phenotype. At the initial presentation, 53% of patients had invasive disease, while 47% were diagnosed with noninvasive disease. During follow-up, 37% of those with noninvasive disease appeared to progress to invasive disease within 1 year. At the point when invasive disease was diagnosed, pT1 disease was observed in 77% cases, and pT2-4 was observed in 23%. During subsequent follow-up, 77% of patients experienced recurrences, with 41% requiring therapeutic escalation to intravesical Bacillus Calmette-Guérin or systemic chemotherapy for disease progression. High-grade recurrence was identified in 23% patients. Distant metastases developed in 18% of patients, preferentially involving the lungs and bone. The median survival of the cohort was 66 months, and 1 patient died of disease. These findings underscore the variable and unpredictable course of this disease phenotype, emphasizing its potential for aggressive evolution despite surface low-grade tumor histology. Vigilant surveillance and early consideration of definitive treatment may be a prudent strategy to mitigate progression risks in this rare subset of patients.
The health care workforce faces challenges globally, including shortages driven by aging populations and workforce burnout, compounded by rapid technological and care delivery transformations. This article examines international case studies developed by the Future of Health, a global network of senior health leaders, to identify strategies for cultivating a resilient and adaptive health workforce. The authors highlight three key approaches: (1) harnessing technology to streamline clinical workflows and reduce administrative burden, (2) reforming existing roles to optimize skills and expand scope, and (3) introducing new professions to address emerging clinical and operational needs. Case examples include the use of artificial intelligence-powered ambient scribes to improve clinician documentation, the certification of caregivers, and the integration of medical data analysts into clinical teams. This analysis emphasizes the importance of fostering workforce trust, navigating regulatory and payment barriers, and deploying thoughtful change management. These strategies offer actionable guidance for policy makers, health system leaders, and clinicians seeking to create a flexible and efficient workforce able to meet evolving patient needs and technological advances.