Supernatant fluid from endobronchial ultrasound-guided transbronchial needle aspiration for rapid next-generation sequencing.

INTRODUCTION: There is an increasing demand to optimize the workflow and maximize tissue available for next-generation sequencing (NGS) for non-small cell carcinoma. We looked at transbronchial needle endobronchial ultrasound-guided bronchoscopy with transbronchial needle aspiration samples and evaluated the performance of supernatant (SN) fluid processed from a dedicated aspirate collected for NGS testing. MATERIALS AND METHODS: Nineteen samples were collected and processed using a new workflow. Five aspirates were collected in formalin. One additional dedicated pass was collected fresh and centrifuged. The resulting cell pellet was added to formalin for cell block (CB) processing. DNA and RNA were extracted from concentrated SN for targeted testing using the Oncomine Precision Assay (Thermo Scientific, Waltham, MA). NGS results from the corresponding CB samples were used as "controls" for comparison. RESULTS: Thirty-one mutations were detected in SN (Table 1). The most frequently mutated genes were TP53 (35%), EGFR (23%), KRAS (13%), CTNNB1 (6%), and ERBB2 (6%). There was 100% concordance between the mutations detected in SN and corresponding CBs with comparable variant allele frequencies. Turnaround time of NGS results was 1 day for SN compared to 4-10 days for CB. CONCLUSIONS: We were able to demonstrate the usefulness of SN for reliable rapid molecular results. We successfully incorporated the workflow for tissue handling and processing among our clinical, cytopathology, and molecular teams. Molecular results were available at the same time as the cytologic diagnosis, allowing for timely reporting of a comprehensive diagnosis. This approach is particularly useful in patients with advanced disease requiring urgent management.

Contribution of systemic factors on macular vessel density: a sex-specific population-based study.

PURPOSE: To evaluate the influence of systemic factors on macular vessel density in quantitative Optical Coherence Tomography Angiography (OCTA) by sex. STUDY DESIGN: A cross-sectional study. METHODS: A total of 2018 adults were recruited in this study. Participants were excluded (n=964) due to missing data, eye-related problems, or low OCTA scan quality. Macular vessel densities were measured with OCTA using split-spectrum amplitude decorrelation angiography algorithm. Only the data from the right eyes were selected for analysis. Multivariable linear regression analysis was performed to determine the associations between macular vessel density and obesity-related systemic factors in each gender group. RESULTS: The right eyes of 1054 participants (59.6% women) were enrolled. Men had significantly higher obesity parameters and associated risk factors. In multivariable linear regression analysis in men, older age and type 2 diabetes mellitus were independently associated with lower superficial retinal vessel density (ß = -0.37, p = 0.002; ß = -1.22, p = 0.03) and deep retinal vessel density, respectively (ß = -0.66, p < 0.001; ß = -1.76, p = 0.02); positive association was also observed between body mass index (BMI) and superficial retinal vessel density (ß = 0.56, p = 0.02). In women, only higher systolic blood pressure was independently associated with a lower deep retinal vessel density (ß = -0.50, p = 0.003). CONCLUSIONS: This large cross-sectional study shows that older age and type 2 diabetes mellitus are associated with lower superficial and deep retinal capillary vessel density in men. This may help clinicians better understand how systemic factors influence retinal vessel density in different genders and future studies can ascertain more potential sex differences.

Spatial comparison of molecular features associated with resistance to pembrolizumab in BCG unresponsive bladder cancer.

Intravenous immune checkpoint inhibition achieves a 40% 3-month response in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ. Yet, only half of the early responders will continue to be disease-free by 12 months, and resistance mechanisms are poorly defined. We performed spatial profiling of BCG-unresponsive tumors from patients responsive or resistant to intravenous pembrolizumab treatment, analyzing samples both before initiating and 3 months post-intravenous pembrolizumab treatment. We analyzed 119 regions of interest, which included 59 pairs of epithelial and adjacent stromal segments across five patients: two responders and three non-responders. We demonstrate that BCG unresponsive tumors with an inflamed PanCK+ tumor area and an infiltrated stromal segment respond better to intravenous pembrolizumab. Furthermore, using segment-specific gene signatures generated from a cohort of BCG unresponsive NMIBC treated with intravesical BCG+pembrolizumab, we find that non-inflamed, immune-cold tumors that do not respond to intravenous pembrolizumab exhibit a favorable outcome to the combined application of BCG and pembrolizumab. For the first time, we have identified molecular features of tumors associated with response and resistance to intravenous pembrolizumab in BCG unresponsive NMIBCs. Further research with more patients and alternative checkpoint inhibitors is essential to validate our findings. We anticipate that using a transcriptomics signature like the one described here can help identify tumors with a higher possibility of responding to intravenous pembrolizumab.

Safety and Diagnostic Efficacy of Image-Guided Biopsy of Small Renal Masses.

INTRODUCTION: Image-guided renal mass biopsy is gaining increased diagnostic acceptance, but there are limited data concerning the safety and diagnostic yield of biopsy for small renal masses (≤4 cm). This study evaluated the safety, diagnostic yield, and management after image-guided percutaneous biopsy for small renal masses. METHODS: A retrospective IRB-approved study was conducted on patients who underwent renal mass biopsy for histopathologic diagnosis at a single center from 2015 to 2021. Patients with a prior history of malignancy or a renal mass >4 cm were excluded. Descriptive statistics were used to summarize patient demographics, tumor size, the imaging modality used for biopsy, procedure details, complications, pathological diagnosis, and post-biopsy management. A biopsy was considered successful when the specimen was sufficient for diagnosis without need for a repeat biopsy. Complications were graded according to the SIR classification of adverse events. A chi-squared test (significance level set at p ≤ 0.05) was used to compare the success rate of biopsies in different lesion size groups. RESULTS: A total of 167 patients met the inclusion criteria. The median age was 65 years (range: 26-87) and 51% were male. The median renal mass size was 2.6 cm (range: one-four). Ultrasound was solely employed in 60% of procedures, CT in 33%, a combination of US/CT in 6%, and MRI in one case. With on-site cytopathology, the median number of specimens obtained per procedure was four (range: one-nine). The overall complication rate was 5%. Grade A complications were seen in 4% (n = 7), consisting of perinephric hematoma (n = 6) and retroperitoneal hematoma (n = 1). There was one grade B complication (0.5%; pain) and one grade D complication (0.5%; pyelonephritis). There was no patient mortality within 30 days post-biopsy. Biopsy was successful in 88% of cases. A sub-group analysis showed a success rate of 85% in tumors <3 cm and 93% in tumors ≥3 cm (p = 0.01). Pathological diagnoses included renal cell carcinoma (65%), oncocytoma (18%), clear cell papillary renal cell tumors (9%), angiomyolipoma (4%), xanthogranulomatous pyelonephritis (1%), lymphoma (1%), high-grade papillary urothelial carcinoma (1%), and metanephric adenoma (1%), revealing benign diagnosis in 30% of cases. The most common treatment was surgery (40%), followed by percutaneous cryoablation (22%). In total, 37% of patients were managed conservatively, and one patient received chemotherapy. CONCLUSION: This study demonstrates the safety and diagnostic efficacy of image-guided biopsy of small renal masses. The diagnostic yield was significantly higher for masses 3-4 cm in size compared to those <3 cm. The biopsy results showed a high percentage of benign diagnoses and informed treatment decisions in most patients.

Chromophobe Renal Cell Carcinoma with Sarcomatoid Differentiation: Clinicopathologic Correlation and Molecular Findings.

Introduction: Sarcomatoid differentiation has been reported in approximately 8% of chromophobe renal cell carcinoma (RCC) and is associated with a worse prognosis. We aim to describe the clinicopathologic and molecular findings of chromophobe RCC with sarcomatoid differentiation. Methods: Surgical pathology database was searched to identify chromophobe RCC with sarcomatoid differentiation from January 2015 to December 2021. Results: Five patients were diagnosed with chromophobe RCC with sarcomatoid differentiation. The median age at the time of diagnosis was 57 years (range 51-61 years). Three patients died after median follow-up of 12.1 months (range 1.6-18.2 months). The median tumor size was 10.7 cm (range 5.6-13.6 cm). The median percentage of sarcomatoid component was 60% (range 10-90%), and the median percentage of necrosis was 30% (range 10-50%). One tumor demonstrated osteoid formation. PAX8, keratin 7, KIT (CD117), and Hale colloidal iron were positive in the epithelial component, whereas the sarcomatoid component was positive for vimentin, CD10, and high Ki67 proliferative index. Molecular testing was performed in three specimens: all were TP53 mutated and microsatellite stable. One aggressive tumor had RB1 frameshift mutation and copy number gains for TERT and CUL4A. Conclusion: Chromophobe RCC with sarcomatoid differentiation is a rare entity with aggressive behavior. Percentage of sarcomatoid component, necrosis, and the occurrence of metastasis is associated with worse prognosis. Molecular profiling reveals frequent TP53 mutation. While TERT promoter mutation has no prognostic implication, FLCN inactivation may be associated with a less aggressive course. The clinical significance of RB1 loss is unclear.

What's new in genitourinary pathology 2023: WHO 5th edition updates for urinary tract, prostate, testis, and penis.

The 5th edition WHO Classification of Urinary and Male Genital Tumours (2022) introduced many significant changes relevant to urologic daily practice, mainly to renal tumors which was covered in the What's New newsletter in September 2022. In this newsletter, we summarize the notable changes to bladder, prostate, testis, and penis based on the 5th edition of the WHO.

A Spatial Comparison of Molecular Features Associated with Resistance to Pembrolizumab in BCG Unresponsive Bladder Cancer.

Background: Intravenous immune checkpoint inhibition achieves a 40% three-month response in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). Yet only half of early responders will continue to be disease free by 12 months, and resistance mechanisms are poorly defined. Objective: We assessed the molecular features associated with response to immunotherapy in BCG unresponsive non-muscle invasive bladder cancers treated with pembrolizumab. Design Setting and Participants: We performed digital spatial profiling (DSP) of BCG unresponsive NMIBC tumors before and after IV pembrolizumab therapy. Intervention: Pembrolizumab was administered intravenously in patients with NMIBC at the time of recurrence after BCG therapy. Biopsies were obtained before starting IV pembrolizumab and three months post-treatment. Outcomes and Statistical Analysis: Spatial gene expression profiling of the tumor niche pre- and post IV pembrolizumab. Results and Limitations: We evaluated 119 regions of interest (ROIs) from five patients, which included 60 epithelial (PanCK+) and 59 stromal segments (PanCK-). ROIs from responders had distinct expression signatures from non-responders for both the tumor and TME. Responders were more likely to have a dynamic change in expression after pembrolizumab than non-responders. A major limitation of this study was the number of patients evaluated. Conclusion: For the first time, we have identified distinct expression signatures associated with response and resistance to IV pembrolizumab in NMIBCs. Further research with more patients and alternative checkpoint inhibitors is essential to validate our findings. Patient Summary: We identify the molecular features of tumors associated with response to pembrolizumab for patients with BCG unresponsive NMIBCs.

From principles to practice: Implementation of entrustable professional activities (EPAs) for surgical pathology residency education in a large academic hospital.

Over the past decade, competency-based medical education (CBME) has gained momentum in the United States to develop trainees into independent and confident physicians by the end of their training. Entrustable professional activities (EPAs) are an established methodology for assessing trainee development through an outcomes-driven rather than a time-based model. While EPAs have been utilized as an assessment tool for CBME in Europe and Canada, their validation and implementation in some medical specialties has occurred more recently in the United States. Pediatrics was the first specialty in the US to conduct a large-scale UME-GME pilot. Pathology Residency EPAs were published in 2018; however, implementation in training programs has been slow. We have piloted EPAs in our residency program's surgical pathology rotation and propose a unique set of 4 surgical pathology EPAs to track trainee preparedness for independent practice.

Sector-Based Regression Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: This cross-sectional study aimed to investigate the sectoral variance of optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters across eyes with varying degrees of refractive error. Methods: Healthy participants, including individuals with axial ametropia, enrolled in the Hong Kong FAMILY cohort were imaged using the Avanti/AngioVue OCT/OCTA system. The OCT and OCTA parameters obtained include peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), and macular ganglion cell complex thickness (GCCT). Sectoral measurements of NFLT, NFLP-CD, and GCCT were based on sectors and hemispheres. Results: A total of 1339 eyes from 791 participants were stratified based on spherical equivalent refraction: high myopia (<-6 D), low myopia (-6 D to -1 D), emmetropia (-1 D to 1 D), and hyperopia (>1 D). Multivariable broken stick regression models, accounting for age, sex, and signal strength, showed that all NFLT sectors except temporally, the inferior GCCT hemisphere, and half of the NFLP-CD sectors were more affected by ametropia-related covariates than the corresponding global parameters. As expected, the false-positive rates in those sectors were elevated. Finally, sector-specific axial length (AL) and spherical equivalent (SE) adjustments helped reduce the elevated false-positive rates. Conclusions: The effect of optical magnification is even more prominent among sectors than the global parameters. AL- and SE-based adjustments should be individualized to each sector to mitigate this magnification bias effectively. Translational Relevance: Identifying sectoral differences among diagnostic parameters and adopting these sector-based adjustments into commercial OCT systems will hopefully reduce false-positive rates related to refractive error.

Expression-based subtypes define pathologic response to neoadjuvant immune-checkpoint inhibitors in muscle-invasive bladder cancer.

Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identify five distinctive genetic and transcriptomic programs and validate these in an independent neoadjuvant CPI trial to identify the features of response or resistance to CPI. By modeling the regulatory network, we identify the histone demethylase KDM5B as a repressor of tumor immune signaling pathways in one resistant subtype (S1, Luminal-excluded) and demonstrate that inhibition of KDM5B enhances immunogenicity in FGFR3-mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy.

Role of renal mass biopsy for diagnosis and management: Review of current trends and future directions.

The frequency of detection of renal masses has increased over recent decades, causing a concurrent increase in early intervention by surgery. Growing recognition that this approach was contributing to overtreatment led to the broader use of preoperative renal mass biopsy (RMB) by core biopsy and/or fine-needle aspiration. Because more options for management, such as active surveillance and personalized therapy, are becoming increasingly available, a diagnosis by RMB is becoming a valuable tool for risk stratification and clinical decision making. Guidelines from various professional organizations have outlined situations in which RMB should be used, and it has been shown to be safe and effective. Rapid on-site evaluation (ROSE) using touch preparations of core biopsy or fine-needle aspiration smears provides an immediate assessment of adequacy and appropriate triage. ROSE also ensures sufficient material to perform immunohistochemistry and molecular studies for more accurate characterization of renal masses and personalized treatment. The integral role of cytopathology laboratories in precision medicine can also be successfully used in optimizing the workup of RMB from ROSE to final diagnosis, prognostication, and personalized management of kidney tumors. Herein, the authors review their extensive experience working together with interventional radiology and urology colleagues to use core biopsy and ROSE at the time of RMB for diagnosis and management of these lesions.

Randomized Control Trial of the Impact of Patient Decision Aid Developed for Chinese Primary Open-Angle Glaucoma Patients.

INTRODUCTION: Patient decision aid (PDA) is a tool to prompt shared decision-making. The aim of this study was to evaluate the impact of a PDA on Chinese primary open-angle glaucoma patients. METHODS: All subjects were randomized into control and PDA group. The questionnaires, including 1) glaucoma knowledge; 2) 8-item Morisky medication adherence scale (MMAS-8); 3) 10-item glaucoma medication adherence self-efficacy scale (GMASES-10); and 4) 16-item decision conflict scale (DCS), were evaluated at baseline, 3- and 6-month follow-up. RESULTS: Totally, 156 subjects participated in this study, including 77 in the control group and 79 in the PDA group. Compared to the control group, PDA group showed around 1 point more improvement in disease knowledge at both 3 and 6 months (both p < 0.05), 2.5 (95% CI: [1.0, 4.1]) and 1.9 (95% CI: [0.2, 3.7]) points more improvement in GMASES-10 at 3 and 6 months, respectively, and reduction in DCS by 8.8 (95% CI: [4.6, 12.9]) points more at 3 months and 13.5 (95% CI: [8.9, 18.0]) points more at 6 months. No difference was detected in MMAS-8. CONCLUSION: PDA led to improvement in disease knowledge and self-confidence in medication adherence and reduced decision conflict compared to control group for at least 6 months.

OCTA biomarkers in adults aged 50 and above: a prospective and cross-sectional community-based study.

BACKGROUND/AIMS: To assess the normative values and parameters of optical coherence tomography angiography (OCTA) influencing the best corrected visual acuity (BCVA) in adults aged 50 and above. METHODS: This was a prospective cross-sectional study from an eye screening programme in Hong Kong for 4188 citizens aged 50 and above. Images were analysed using a validated quantification software calculating vessel density and capillary perfusion density (CPD), along with other OCTA parameters, such as the foveal avascular zone area (FAZ) and circularity. OCTA data was collected from May 2019 to December 2020, including a total of 4188 healthy eyes from 4188 subjects. RESULTS: Mean superficial vessel density (MSVD) was 14.48 ± 3.60 mm- 1, while the mean capillary perfusion density (MCPD) was 0.41 ± 0.06. Multivariate analysis revealed ageing (ß = 0.321, p < 0.001), being male (ß=-0.089, p < 0.001), having a high body mass index (BMI) (ß = 0.039, p = 0.006), high FAZ area and low FAZ circularity (ß = 0.039 and - 0.034, p = 0.01 and 0.024 respectively), low MSVD in the outer ring (ß=-0.513, p < 0.001), specifically in the nasal and temporal outer quadrants (ß = -0.226 and - 0.259, p < 0.001 for both), and low MCPD in the outer superior quadrant (ß= -0.123, p = 0.016) being independently associated with BCVA. CONCLUSION: High FAZ area and low FAZ circularity, low MSVD in the outer ring, specifically the nasal and temporal outer quadrants, and low MCPD in the outer superior quadrant can be used as biomarkers in predicting a low visual acuity in adults aged 50 and above.

Cytomorphology of renal angiomyolipoma: performance and accuracy of touch preparation of core needle biopsy.

INTRODUCTION: The recognition of renal angiomyolipoma (AML) can be challenging based on cytology preparations such as touch preparation (TP) of core needle biopsy (CNB) and fine needle aspiration. This study evaluated the cytologic features and performance of TP of CNB during rapid onsite evaluation (ROSE) of renal AML. MATERIALS AND METHODS: A pathology database search was performed between 2000 and 2021 for renal CNB specimens with ROSE using TP that were primarily favored AML on preliminary impression and/or confirmed AML on CNB or subsequent resection. RESULTS: Twenty confirmed AML were identified (90% female, median age 65.5 years). Sixteen (80%) were deemed adequate for diagnosis at the time of ROSE, and 9 of 16 (56%) had available onsite impression: AML was favored in 4 of 9 cases (44%). Examination of TP slides revealed spindle/epithelioid cells in 20 (100%), adipose tissue in 14 (70%), and blood vessels in 3 (15%). All AML cases were subsequently confirmed by immunohistochemistry. Additionally, 3 other cases with ROSE favoring AML revealed to be "renal parenchyma with fibrosis," clear cell papillary renal cell tumor and clear cell renal cell carcinoma. CONCLUSIONS: Onsite evaluation of TP ensures adequate material for diagnosis in most renal AML. Spindle/epithelioid cells were the most common component seen on TP, followed by adipose tissue. Blood vessels were rarely seen. While the recognition of AML at ROSE can be challenging, proper evaluation is important in obtaining adequate diagnostic tissue. Correlation with CNB and utilization of immunohistochemistry are crucial for arriving at the diagnosis.

Psychological interventions to reduce intraocular pressure (IOP) in glaucoma patients: a review.

PURPOSE: Glaucoma has been increasing recognised to cause significant mental health burden to patients while psychological factors also play important roles in the development and progression of glaucoma. This review presents the current evidence of the impact of psychological interventions in glaucoma patients to improve their holistic care in terms of both physical and mental health by modulating psychological symptoms and supporting glaucoma control. METHODS: A literature search was conducted on PubMed for relevant studies up to February 2022. Types of psychological interventions include meditation, autogenic relaxation, music, hypnosis, motivational interviewing, psychological nursing and bright light exposure. Outcomes investigated were ocular parameters including intraocular pressure, mental health, patient motivation and satisfaction, and overall quality of life. RESULTS: Seventeen studies investigating the effects of psychological interventions on improving the care of glaucoma patients were reviewed. Daily meditation for 30 to 60 min has been shown to be effective in improving glaucoma control in terms of reducing intraocular pressure by 1.5 to 6.1 mmHg and improving ocular perfusion and quality of life. The impacts of music, autogenic training and psychological nursing on glaucoma control, vision outcomes and psychological symptoms are also promising while bright light exposure has shown some effects on sleeping quality. However, there is insufficient basis to support the adoption of motivational interviewing or hypnosis in glaucoma patients yet. CONCLUSION: Psychological interventions, especially meditation, can play a bigger role in the holistic care of glaucoma patients by controlling disease progression as an adjunct to conventional approaches and alleviating the mental health burden caused by the disease through stress reduction and emotional regulation. They empower patients to gain greater control of their disease and provides additional advantages of low cost, non-invasiveness and minimal side effects. Future research should involve well-conducted randomised trials with larger sample sizes and longer duration of intervention and follow-up to establish the long-term benefits for glaucoma patients.

Distribution of multiple chalazia in eyelids of pediatrics requiring surgery in southeast China: a hospital-based cross-sectional study.

Background: Multiple chalazia are common in children, and many are treated by surgery. However, the distribution of different types of multiple chalazia has not been studied. This research aimed to investigate the location and number of multiple chalazia in pediatrics who need surgical treatments. Methods: Patients with multiple chalazia treated by incision and curettage surgery (I&C) in a tertiary children's hospital between June and December 2016 were reviewed. Demographic data, locations, and numbers of chalazia were recorded. Data were analyzed using generalized linear models of the counts and the occurrences of chalazia. Hypotheses were tested using likelihood ratio tests appropriate for each type of data. Results: The study included 128 subjects, most of which were 1-3 years old. The majority of patients had bilateral chalazia (95.3%), and the proportions of patients with internal, external, and marginal chalazion differed dramatically (99.2%, 61.7%, and 2.3%, respectively). The number of internal and external chalazia did not vary significantly with gender, age, or residence of the patients. Internal chalazia were located more frequently in the upper lids (p<0.001). External chalazia showed no preference of localization. The average number of internal chalazia in each eyelid did not relate to the presence of external chalazia. Conclusions: Multiple chalazia are common among younger children in southeast China. The anatomical distribution varies depending on the type of chalazion. Multiple chalazia often occur bilaterally and internally. If doctors are more aware of the anatomical distribution of chalazia, this might result in a higher success rate of I&C.

Regression-Based Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: The purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters. Methods: OCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis. Results: A total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (<-6D), low myopia (-6D to -1D), emmetropia (-1D to 1D), and hyperopia (>1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD on axial eye length (AL), spherical equivalent (SE) refraction, and apparent optic disc diameter (DD). Optical analysis indicated that AL-related transverse optical magnification variations predominated over anatomic variations and were responsible for these trends. Compared to the emmetropic group, the false positive rates were significantly (Chi-square test P < 0.003) elevated in both myopia groups for NFLT, NFLP-CD, and GCCT. Regression-based adjustment of these diagnostic parameters with AL or SE significantly (McNemar test P < 0.03) reduced the elevated false positive rates. Conclusions: Myopic eyes are biased to have lower NFLT, GCCT, and NFLP-CD measurements. AL- and SE-based adjustments were effective in mitigating this bias. Translational Relevance: Adoption of these adjustments into commercial OCT systems may reduce false positive rates related to refractive error.

Minimally invasive cytologic evaluation leading to the diagnosis of TFE3-rearranged renal cell carcinoma: A case report.

TFE3-rearranged renal cell carcinoma (RCC) has been categorized as a molecularly defined renal carcinoma in the 2022 WHO classification of tumors as it does not demonstrate a specific genotype-phenotype correlation. However, in order to arrive at the diagnosis, recognition of the broad spectrum of cytologic and histologic features that can be seen in TFE3-rearranged RCC is important for differential diagnostic consideration. Reported here is the diagnostic workup of a TFE3-rearranged RCC using very limited tissue sample. The initial evaluation was dependent on the cytomorphologic findings observed on a touch preparation made from the renal mass biopsy, directing appropriate selection of ancillary tests, and leading to a definitive diagnosis.

First-in-human Intravesical Delivery of Pembrolizumab Identifies Immune Activation in Bladder Cancer Unresponsive to Bacillus Calmette-Guérin.

BACKGROUND: Intravenous immune checkpoint inhibition is an effective anticancer strategy for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) but may be associated with greater systemic toxicity compared with localized therapies. OBJECTIVE: We assessed the safety and antitumor activity of intravesical pembrolizumab combined with BCG. DESIGN, SETTING, AND PARTICIPANTS: A 3 + 3 phase 1 trial of pembrolizumab + BCG was conducted in patients with BCG-unresponsive NMIBC (NCT02808143). INTERVENTION: Pembrolizumab was given intravesically (1-5 mg/kg for 2 h) beginning 2 weeks prior to BCG induction until recurrence. Urine profiling during treatment and spatial transcriptomic profiling of pre- and post-treatment tumors were conducted to identify biomarkers that correlated with response. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Safety and tolerability of immune checkpoint inhibition were assessed, and Kaplan-Meier survival analysis was performed. RESULTS AND LIMITATIONS: Nine patients completed therapy. Median follow-up was 35 months for five patients still alive at the end of the trial. The trial was closed due to the COVID-19 pandemic. Grade 1-2 urinary symptoms were common. The maximum tolerated dose was not reached; however, one dose-limiting toxicity was reported (grade 2 diarrhea) in the only patient who reached 52 weeks without recurrence. One death occurred from myasthenia gravis that was deemed potentially related to treatment. The 6-mo and 1-yr recurrence-free rates were 67% (95% confidence interval [CI]: 42-100%) and 22% (95% CI: 6.5-75%), respectively. Pembrolizumab was detected in the urine and not in blood. CD4+ T cells were significantly increased in the urine after treatment, and a transcriptomic analysis identified decreased expression of T-cell exhaustion markers in late recurrences. CONCLUSIONS: We demonstrate that intravesical pembrolizumab is safe, feasible, and capable of eliciting strong immune responses in a clinical setting and should be investigated further. PATIENT SUMMARY: Direct application of pembrolizumab to the bladder is a promising alternative for non-muscle-invasive bladder cancer unresponsive to Bacillus Calmette-Guérin and should be investigated further.

Efficacy of 0.01% atropine for myopia control in a randomized, placebo-controlled trial depends on baseline electroretinal response.

This study aimed to evaluate the efficacy of 18-month 0.01% atropine in 61 myopic children (aged 7-10) and the relationship with central retinal response (by multifocal electroretinogram [mfERG]) in a double-masked randomized placebo-controlled clinical trial. Global-flash mfERG was measured at baseline, while cycloplegic spherical equivalent refraction (SER) and axial length (AL) were measured at baseline and at 6-month intervals. Annualized change in SER and AL were compared between atropine and control groups, and the relationships with baseline mfERG were evaluated. Changes in SER (-0.70 ± 0.39D vs. -0.66 ± 0.41D, p = 0.63) and AL (0.32 ± 0.16 mm vs. 0.30 ± 0.22 mm, p = 0.52) were similar in atropine and control groups. Interestingly, in the placebo group, mfERG amplitude was negatively correlated with axial elongation (Rp = -0.44, p = 0.03) as in our previous study. However, in the atropine group, an opposite trend was observed that axial elongation was positively correlated with mfERG amplitude (Ra = 0.37, p = 0.04). Annualized myopia progression demonstrated similar opposite effect between atropine and placebo groups but did not reach statistical significance. An ERG screening protocol may be warranted to identify suitable candidates to reduce the likelihood of an unfavorable treatment response by 0.01% atropine.