Metastatic melanoma is associated with a poor prognosis, but no method reliably predicts which melanomas of a given stage will ultimately metastasize and which will not. While sentinel lymph node biopsy (SLNB) has emerged as the most powerful predictor of metastatic disease, the majority of people dying from metastatic melanoma still have a negative SLNB. Here we analyze pump-probe microscopy images of thin biopsy slides of primary melanomas to assess their metastatic potential. Pumpprobe microscopy reveals detailed chemical information of melanin with subcellular spatial resolution. Quantification of the molecular signatures without reference standards is achieved using a geometrical representation of principal component analysis. Melanin structure is analyzed in unison with the chemical information by applying principles of mathematical morphology. Results show that melanin in metastatic primary lesions has lower chemical diversity than non-metastatic primary lesions, and contains two distinct phenotypes that are indicative of aggressive disease. Further, the mathematical morphology analysis reveals melanin in metastatic primary lesions has a distinct "dusty" quality. Finally, a statistical analysis shows that the combination of the chemical information with spatial structures predicts metastatic potential with much better sensitivity than SLNB and high specificity, suggesting pump-probe microscopy can be an important tool to help predict the metastatic potential of melanomas.

Abstract. We demonstrate a multimodal approach that combines a pump-probe with confocal reflectance and multiphoton autofluorescence microscopy. Pump-probe microscopy has been proven to be of great value in analyzing thin tissue sections of pigmented lesions, as it produces molecular contrast which is inaccessible by other means. However, the higher optical intensity required to overcome scattering in thick tissue leads to higher-order nonlinearities in the optical response of melanin (e.g., two-photon pump and one-photon probe) that present additional challenges for interpreting the data. We show that analysis of pigment composition in vivo must carefully account for signal terms that are nonlinear with respect to the pump and probe intensities. We find that pump-probe imaging gives useful contrast for pigmented structures over a large range of spatial scales (100 μm to 1 cm), making it a potentially useful tool for tracking the progression of pigmented lesions without the need to introduce exogenous contrast agents.

INTRODUCTION: Recent studies indicate low rates of follow-up colonoscopy after abnormal fecal immunochemical testing (FIT) within safety net health systems. A patient navigation (PN) program is an evidence-based strategy that has been shown to improve colonoscopy completion in private and public healthcare settings. The aim of this study was to evaluate the effectiveness of a PN program to encourage follow-up colonoscopy after abnormal FIT within a large safety net hospital system. METHODS: We established an enterprisewide PN program at 5 tertiary care hospitals within the Los Angeles County Department of Health Services system in 2018. The PN assisted adult patients aged 50–75 years with an abnormal FIT to a follow-up colonoscopy within 6 months. PN activities included initiating referral for and scheduling of colonoscopy, performing reminder phone calls to patient for their upcoming colonoscopy, and following up with patients who did not attend their colonoscopy. We assess the effectiveness of the PN intervention by comparing follow-up colonoscopy rates with a period before the intervention. RESULTS: There were 2,531 patients with abnormal FIT results (n = 1,214 in 2017 and n = 1,317 in 2018). A majority were women (55% in 2017 vs 52% in 2018) with a mean age of 60 ± 6.2 years. From a previous mean of 163 days without PN in 2017, the mean time from abnormal FIT to colonoscopy with PN improved to 113 days in 2018. The frequency of colonoscopy completion with PN increased from 40.6% (n = 493) in 2017 to 46% (n = 600) in 2018. DISCUSSION: After the introduction of the PN program, there was a significant increase in patients undergoing follow-up colonoscopy after abnormal FIT and patients were more likely to undergo colonoscopy within the recommended 6 months.

Background Hepatocellular carcinoma is one of few cancers with rising incidence and mortality in the United States. Little is known about disease presentation and outcomes across the rural-urban continuum. Methods Using the population-based SEER registry, we identified adults with incident hepatocellular carcinoma between 2000–2016. Urban, suburban and rural residence at time of cancer diagnosis were categorized by the Census Bureau’s percent of the population living in non-urban areas. We examined association between place of residence and overall survival. Secondary outcomes were late tumor stage and receipt of therapy. Results Of 83,368 cases, 75.8%, 20.4%, and 3.8% lived in urban, suburban, and rural communities, respectively. Median survival was 7 months (IQR 2–24). All stage and stage-specific survival differed by place of residence, except for distant stage. In adjusted models, rural and suburban residents had a respective 1.09-fold (95% CI = 1.04–1.14, p < .001) and 1.08-fold (95% CI = 1.05–1.10, p < .001) increased hazard of overall mortality as compared to urban residents. Furthermore, rural and suburban residents had 18% (OR = 1.18, 95% CI 1.10–1.27, p < .001) and 5% (OR = 1.05, 95% CI = 1.02–1.09, p = .003) higher odds of diagnosis at late stage and were 12% (OR = 0.88, 95% CI = 0.80–0.94, p < .001) and 8% (OR = 0.92, 95% CI = 0.88–0.95, p < .001) less likely to receive treatment, respectively, compared to urban residents. Conclusions Residence in a suburban and rural community at time of diagnosis was independently associated with worse indicators across the cancer continuum for liver cancer. Further research is needed to elucidate the primary drivers of these rural-urban disparities.

Background: COVID-19 is associated with higher morbidity and mortality in patients with chronic liver diseases (CLDs). However, our understanding of the long-term outcomes of COVID-19 in patients with CLD is limited. Methods: We conducted a multicenter, observational cohort study of adult patients with CLD who were diagnosed with COVID-19 before May 30, 2020, to determine long-term clinical outcomes. We used a control group of patients with CLD confirmed negative for COVID-19. Results: We followed 666 patients with CLD (median age 58 years, 52.8% male) for a median of 384 (interquartile range: 31–462) days. The long-term mortality was 8.1%; with 3.6% experiencing delayed COVID-19-related mortality. Compared to a propensity-matched control group of patients with CLD without COVID-19 (n=1332), patients with CLD with COVID-19 had worse long-term survival [p<0.001; hazards ratio (HR): 1.69; 95% CI: 1.19–2.41] and higher rate of hospitalization (p<0.001, HR: 2.00, 1.62–2.48) over a 1-year follow-up period. Overall, 29.9% of patients reported symptoms of long-COVID-19. On multivariable analysis, female sex (p=0.05, HR: 2.45, 1.01–2.11), Hispanic ethnicity (p=0.003, HR: 1.94, 1.26–2.99), and severe COVID-19 requiring mechanical ventilation (p=0.028, HR: 1.74, 1.06–2.86) predicted long-COVID-19. In survivors, liver-related laboratory parameters showed significant improvement after COVID-19 resolution. COVID-19 vaccine status was available for 72% (n=470) of patients with CLD and history of COVID-19, of whom, 70% (n=326) had received the COVID-19 vaccine. Conclusions: Our large, longitudinal, multicenter study demonstrates a high burden of long-term mortality and morbidity in patients with CLD and COVID-19. Symptoms consistent with long-COVID-19 were present in 30% of patients with CLD. These results illustrate the prolonged implications of COVID-19 both for recovering patients and for health care systems.

BACKGROUND Endoscopic sleeve gastroplasty (ESG) is an effective therapy for class I-II obesity, but there are knowledge gaps in the published literature about its implementation in patients with class III obesity [body mass index (BMI) ≥ 40 kg/m 2 ]. AIM To evaluate the safety, clinical efficacy, and durability of ESG in adults with class III obesity. METHODS This was a retrospective cohort study that used prospectively collected data on adults with BMI ≥ 40 kg/m 2 who underwent ESG and longitudinal lifestyle counseling at two centers with expertise in endobariatric therapies from May 2018-March 2022. The primary outcome was total body weight loss (TBWL) at 12 mo. Secondary outcomes included changes in TBWL, excess weight loss (EWL) and BMI at various time points up to 36 mo, clinical responder rates at 12 and 24 mo, and comorbidity improvement. Safety outcomes were reported through the study duration. One-way ANOVA test was performed with multiple Tukey pairwise comparisons for TBWL, EWL, and BMI over the study duration. RESULTS 404 consecutive patients (78.5% female, mean age 42.9 years, mean BMI 44.8 ± 4.7 kg/m 2 ) were enrolled. ESGs were performed using an average of 7 sutures, over 42 ± 9 min, and with 100% technical success. TBWL was 20.9 ± 6.2% at 12 mo, 20.5 ± 6.9% at 24 mo, and 20.3 ± 9.5% at 36 mo. EWL was 49.6 ± 15.1% at 12 mo, 49.4 ± 16.7% at 24 mo, and 47.1 ± 23.5% at 36 mo. There was no difference in TBWL at 12, 15, 24, and 36 mo from ESG. TBWL exceeding 10%, 15%, and 20% was achieved by 96.7%, 87.4%, and 55.6% of the cohort at 12 mo, respectively. Of the cohort with the relevant comorbidity at time of ESG, 66.1% had improvement in hypertension, 61.7% had improvement in type II diabetes, and 45.1% had improvement in hyperlipidemia over study duration. There was one instance of dehydration requiring hospitalization (0.2% serious adverse event rate). CONCLUSION When combined with longitudinal nutritional support, ESG induces effective and durable weight loss in adults with class III obesity, with improvement in comorbidities and an acceptable safety profile.

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