Early screening of colorectal cancer using feature engineering with artificial intelligence-enhanced analysis of nanoscale chromatin modifications.

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity of cancer cells. We deployed an optical spectroscopic nanosensing technique, chromatin-sensitive partial wave spectroscopic microscopy (csPWS), to evaluate the packing density scaling D of the chromatin chain conformation within packing domains from rectal mucosa in 256 patients with varying degrees of progression to colorectal cancer. We found average packing scaling D of chromatin domains was elevated in tumor cells, histologically normal-appearing cells 4 cm proximal to the tumor, and histologically normal-appearing rectal mucosa compared to cells from control patients (p < 0.001). Nuclear D had a robust correlation with the model of 5-year risk of CRC with r2 = 0.94. Furthermore, rectal D was evaluated as a screening biomarker for patients with advanced adenomas presenting an AUC of 0.85 and 85% sensitivity and specificity. artificial intelligence-enhanced csPWS improved diagnostic performance with AUC = 0.90. Considering the low sensitivity of existing CRC tests, including liquid biopsies, to early-stage cancers our work highlights the potential of chromatin biomarkers of field carcinogenesis in detecting early, significant precancerous colon lesions.

Case Report: Macula Structural and Functional Assessment in Nab-Paclitaxel-Related Cystoid Macular Edema.

Nab-paclitaxel-related cystoid macular edema is a rare ophthalmic adverse drug reaction. We present a 54-year-old woman with metastatic hormone receptor positive, HER-2 negative breast carcinoma who developed profound bilateral vision loss after the seventh cycle of nab-paclitaxel treatment. Optical coherence tomography and macula microperimetry demonstrated macular edema and decreased threshold sensitivity, respectively. Cessation of nab-paclitaxel improved structural and functional vision after 4 weeks. The introduction of topical dorzolamide 1% in one eye demonstrated further rapid resolution of edema. We demonstrate the objective and subjective visual changes and recovery of nab-paclitaxel-related cystoid macular edema. [Ophthalmic Surg Lasers Imaging Retina 2024;55:xx-xx.].

Rural Women Have a Prolonged Recovery Process after Esophagectomy.

BACKGROUND: Gender and geographic access to care play a large role in health disparities in esophageal cancer care. The aim of our study was to evaluate disparities in peri-operative outcomes for patients undergoing esophagectomy based on gender and geographic location. METHODS: A retrospective cohort of prospectively collected data from patients who underwent esophagectomy from 2003 to 2022 was identified and analyzed based on gender and county, which were aggregated into existing state-level "metropolitan" versus "rural" designations. The demographics, pre-operative treatment, surgical complications, post-operative outcomes, and length of stay (LOS) of each group were analyzed using chi-squared, paired t-tests and single-factor ANOVA. RESULTS: Of the 1545 patients, men (83.6%) and women (16.4%) experienced similar rates of post-operative complications, but women experienced significantly longer hospital (p = 0.002) and ICU (p = 0.03) LOSs as compared with their male counterparts, with no differences in 30-day mortality. When separated by geographic criteria, rural women were further outliers, with significantly longer hospital LOSs (p < 0.001) and higher rates of ICU admission (p < 0.001). CONCLUSIONS: Rural female patients undergoing esophagectomy were more likely to have a longer inpatient recovery process compared with their female metropolitan or male counterparts, suggesting a need for more targeted interventions in this population.

Pathogenic Roles for RNASET2 in Clear Cell Renal Cell Carcinoma.

A specific splicing isoform of RNASET2 is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). However, the interplay between wild-type RNASET2 and its splice variant and how this might contribute to the pathogenesis of ccRCC remains poorly understood. We sought to better understand the relationship of RNASET2 in the pathogenesis of ccRCC and the interplay with a pathogenic splicing isoform (RNASET2-SV) and the tumor immune microenvironment. Using data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium, we correlated clinical variables to RNASET2 expression and the presence of a specific RNASET2-SV. Immunohistochemical staining with matched RNA sequencing of ccRCC patients was then utilized to understand the spatial relationships of RNASET2 with immune cells. Finally, in vitro studies were performed to demonstrate the oncogenic role of RNASET2 and highlight its potential mechanisms. RNASET2 gene expression is associated with higher grade tumors and worse overall survival in The Cancer Genome Atlas cohort. The presence of the RNASET2-SV was associated with increased expression of the wild-type RNASET2 protein and epigenetic modifications of the gene. Immunohistochemical staining revealed increased intracellular accumulation of RNASET2 in patients with increased RNA expression of RNASET2-SV. In vitro experiments reveal that this accumulation results in increased cell proliferation, potentially from altered metabolic pathways. RNASET2 exhibits a tumor-promoting role in the pathogenesis of ccRCC that is increased in the presence of a specific RNASET2-SV and associated with changes in the cellular localization of the protein.

Impact of cryoablation on operative outcomes in thoracotomy patients.

OBJECTIVES: Cryoablation is increasingly being utilized as an alternative to epidurals for patients undergoing thoracotomies. Current evidence suggests cryoablation may decrease postoperative analgesia utilization, but could increase operative times. We hypothesized that the adoption of intraoperative cryoablation to manage post-thoracotomy pain would result in reduced length of stay and reduced perioperative analgesia compared to routine epidural use. METHODS: A retrospective analysis was performed from a single, quaternary referral centre, prospective database on patients receiving thoracotomies between January 2020 and March 2022. Patients undergoing transthoracic hiatal hernia repair, lung resection or double-lung transplant were divided between epidural and cryoablation cohorts. Primary outcomes were length of stay, intraoperative procedure time, crossover pain management and oral narcotic usage the day before discharge. RESULTS: During the study period, 186 patients underwent a transthoracic hiatal hernia repair, lung resection or double-lung transplant with 94 receiving a preoperative epidural and 92 undergoing cryoablation. Subgroup analysis demonstrated no significant differences in demographics, operative length, length of stay or perioperative narcotic use. Notably, over a third of patients in each cryoablation subgroup received a postoperative epidural (45.5% transthoracic hiatal hernia repair, 38.5% lung resection and 45.0% double-lung transplant) for further pain management during their admission. CONCLUSIONS: Cryoablation use was not associated with an increase in procedure time, a decrease in narcotic use or length of stay. Surprisingly, many cryoablation patients received epidurals in the postoperative period for further pain control. Additional analysis is needed to fully understand the benefits and costs of epidural versus cryoablation strategies.

Comprehensive sampling of the lung microbiome in early-stage non-small cell lung cancer.

Objectives: Data are scarce on whether the composition of the lung microbiome (extending from the nasopharynx to the peripheral lung tissue) varies according to histology or grade of non-small cell lung cancer. We hypothesized that the composition of the lung microbiome would vary according to the histology and the grade of non-small cell lung cancer. Methods: We collected naso-oral and central lobar (cancer affected, ipsilateral unaffected, and contralateral unaffected) bronchoalveolar lavage fluid and brushing samples from patients with clinical early-stage lung cancer between July 2018 and February 2020 at a single academic center. We performed bacterial 16S rRNA sequencing and then compared clinical and pathologic findings with microbiome signatures. Results: Samples were collected from 28 patients. Microbial composition in affected lobes displayed unique enrichment of oropharyngeal bacterial species that was significantly different compared with that from the unaffected contralateral lobes; patients with chronic obstructive pulmonary disease had similar diversity to those without chronic obstructive pulmonary disease (P = .1312). The lung microbiome diversity in patients with adenocarcinoma was similar to those with squamous cell cancer (P = .27). There were no differences in diversity or composition in the unaffected lobes of patients with adenocarcinoma versus squamous cell cancer. There was a trend toward lower lung microbial diversity in poorly differentiated adenocarcinomas compared with well-differentiated adenocarcinomas (P = .08). Conclusions: The lung microbiota differs between cancer affected and unaffected lobes in the same patient. Furthermore, poorly differentiated lung cancers were associated with lower microbial diversity. Larger studies will be required to confirm these findings.

Racial and ethnic inequities in the quality of paediatric care in the USA: a review of quantitative evidence.

Racial and ethnic inequities in paediatric care have received increased research attention over the past two decades, particularly in the past 5 years, alongside an increased societal focus on racism. In this Series paper, the first in a two-part Series focused on racism and child health in the USA, we summarise evidence on racial and ethnic inequities in the quality of paediatric care. We review studies published between Jan 1, 2017 and July 31, 2022, that are adjusted for or stratified by insurance status to account for group differences in access, and we exclude studies in which differences in access are probably driven by patient preferences or the appropriateness of intervention. Overall, the literature reveals widespread patterns of inequitable treatment across paediatric specialties, including neonatology, primary care, emergency medicine, inpatient and critical care, surgery, developmental disabilities, mental health care, endocrinology, and palliative care. The identified studies indicate that children from minoritised racial and ethnic groups received poorer health-care services relative to non-Hispanic White children, with most studies drawing on data from multiple sites, and accounting for indicators of family socioeconomic position and clinical characteristics (eg, comorbidities or condition severity). The studies discussed a range of potential causes for the observed disparities, including implicit biases and differences in site of care or clinician characteristics. We outline priorities for future research to better understand and address paediatric treatment inequities and implications for practice and policy. Policy changes within and beyond the health-care system, discussed further in the second paper of this Series, are essential to address the root causes of treatment inequities and to promote equitable and excellent health for all children.

The prognostic impact of tumor length on pathological stage IA-IC esophageal adenocarcinoma.

This study was completed to evaluate the relationship between tumor length and the prognosis of patients with pathological stage IA-IC esophageal adenocarcinoma (EAC). Patients were identified from the Surveillance, Epidemiology, and End Results Program database (United States, 2006-2015). X-tile software and ROC analysis were mainly used to explore the best threshold of tumor length for dividing patients into different groups, and then propensity score matching (PSM) was used to balance other variables between groups. The primary outcome assessed was overall survival (OS). A total of 762 patients were identified, and 500 patients were left after PSM. Twenty millimeters were used as the threshold of tumor length. Patients with longer tumor lengths showed worse OS (median: 93 vs. 128 months; P = 0.006). Multivariable Cox regression analysis showed that longer tumor length was an independent risk factor (hazard ratio 1.512, 95% confidence interval, 1.158-1.974, P = 0.002). Tumor length has an impact on patients with pathological stage IA-IC EAC who undergo surgery alone. The prognostic value of the pathological stage group may be improved after combining it with tumor length and age.

KESTREL and KITE Phase 3 Studies: 100-Week Results With Brolucizumab in Patients With Diabetic Macular Edema.

PURPOSE: To report the 100-week outcomes from the KESTREL and KITE trials. DESIGN: Two phase 3, double-masked, active-controlled, randomized trials. METHODS: Patients with diabetic macular edema (DME) were randomized 1:1:1 to brolucizumab 3 mg/6 mg (BRO3/BRO6) or aflibercept 2 mg (AFL) in KESTREL (N = 566) or 1:1 to BRO6 or AFL in KITE (N = 360). BRO3/BRO6 arms received 5 loading doses every 6 weeks (q6w) followed by q12w dosing, with an option to adjust to q8w at predefined disease activity assessment visits. In KITE, at week 72, based on the disease stability assessment, treatment intervals could be extended by 4 weeks in the BRO6 arm. AFL arms received 5 monthly loading doses followed by fixed q8w dosing. RESULTS: At week 100, change from baseline in BCVA (letters) was +8.8 for BRO6 and +10.6 for AFL in KESTREL; and +10.9 for BRO6 and +8.4 for AFL in KITE. In both studies, fewer BRO6 subjects had intraretinal fluid and/or subretinal fluid than AFL subjects. Results were achieved with 32.9% (KESTREL) and 47.5% (KITE) of BRO6 subjects maintained on q12w and q12w/q16w dosing, respectively. Intraocular inflammation rates for BRO6 vs AFL were 4.2% vs 1.1% (KESTREL) and 2.2% vs 1.7% (KITE), of which retinal vasculitis rates were 0.5% vs 0% in KESTREL, with no cases in KITE. Retinal vascular occlusion rates were 1.6% vs 0.5% (KESTREL) and 0.6% in both treatment arms in KITE. CONCLUSIONS: Results show the long-term efficacy and durability of brolucizumab in improving visual and anatomical outcomes in DME; the overall safety profile of brolucizumab remained unchanged through year 2.

Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen.

BACKGROUND: To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice. METHODS: This was a multicentre, retrospective comparative study. Totally, 202 treatment-naïve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n = 105) or reactive (n = 97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion's margins from serial OCT images and growth rates were calculated. RESULTS: At baseline, the mean [SD] lesion area was 7.24 [5.6] mm2 in the proactive group and 6.33 [4.8] mm2 in the reactive group respectively (p = 0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5] mm2 showing a significant reduction compared to the baseline (p < 0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0] mm2 at four years (p < 0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions. CONCLUSIONS: Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.

PIGMENT EPITHELIAL DETACHMENT THICKNESS AND VARIABILITY AFFECTS VISUAL OUTCOMES IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the impact of pigment epithelial detachment (PED) thickness (i.e., height) and thickness variability on best-corrected visual acuity outcomes in patients with neovascular age-related macular degeneration in the Phase 3 HAWK and HARRIER trials. METHODS: Optical coherence tomography images from the pooled brolucizumab 6 mg and aflibercept 2 mg arms were analyzed for the maximum PED thickness across the macula at baseline through to week 96. Best-corrected visual acuity outcomes were compared in patients with different PED thickness and variability cut-off thresholds. RESULTS: Greater PED thickness at baseline or at week 12 was associated with lower mean best-corrected visual acuity gain from baseline to week 96 (baseline PED ≥200 µ m: +4.6 letters; <200 µ m: +7.0 letters; week 12 PED ≥100 µ m: +5.6 letters; <100 µ m: +6.6 letters). Eyes with the largest PED thickness variability from week 12 through week 96 gained fewer letters from baseline at week 96 (≥33 µ m: +3.3 letters; <9 µ m: +6.2 letters). Furthermore, increased PED thickness at week 48 was associated with higher prevalence of intraretinal and subretinal fluid. CONCLUSION: In this treatment-agnostic analysis, greater PED thickness and PED thickness variability were associated with poorer visual outcomes in patients with neovascular age-related macular degeneration and greater neovascular activity.

Factors affecting timing of surgery following neoadjuvant chemoradiation for esophageal cancer.

Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal cancer. Studies have shown that surgical timing following chemoradiation is important for minimizing postoperative complications, however in practice timing is often variable and delayed. Although postoperative impact of surgical timing has been studied, less is known about factors associated with delays. Materials and methods: A retrospective review was performed for 96 patients with esophageal cancer who underwent chemoradiation then esophagectomy between 2018 and 2020 at a single institution. Univariable and stepwise multivariable analyses were used to assess association between social (demographics, insurance) and clinical variables (pre-operative weight, comorbidities, prior cardiothoracic surgery, smoking history, disease staging) with time to surgery (≤8 weeks "on-time" vs. >8 weeks "delayed"). Results: Fifty-one patients underwent esophagectomy within 8 weeks of chemoradiation; 45 had a delayed operation. Univariate analysis showed the following characteristics were significantly different between on-time and delayed groups: weight loss within 3 months of surgery (3.9 ± 5.1 kg vs. 1.5 ± 3.6 kg; P = 0.009), prior cardiovascular disease (29% vs. 49%; P = 0.05), prior cardiothoracic surgery (4% vs. 22%; P = 0.01), history of ever smoked (69% vs. 87%; P = 0.04), absent nodal metastasis on pathology (57% vs. 82%; P = 0.008). Multivariate analysis demonstrated that prior cardiothoracic surgery (OR 8.924, 95%CI 1.67-47.60; P = 0.01) and absent nodal metastasis (OR 4.186, 95%CI 1.50-11.72; P = 0.006) were associated with delayed surgery. Conclusions: Delayed esophagectomy following chemoradiotherapy is associated with prior cardiothoracic surgery and absent nodal metastasis. Further investigations should focus on understanding how these factors contribute to delays to guide treatment planning and mitigate sources of outcome disparities.

Early screening of colorectal cancer using feature engineering with artificial intelligence-enhanced analysis of nanoscale chromatin modifications.

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~7-8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~5-20 nm, ~1 kbp) fold into chromatin packing domains (~100-200 nm, ~100-1,000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity of cancer cells. We deployed an optical spectroscopic nanosensing technique, chromatin-sensitive partial wave spectroscopic microscopy (csPWS), to evaluate the packing density scaling D of the chromatin chain conformation within packing domains from rectal mucosa in 256 patients with varying degrees of progression to colorectal cancer. We found average packing scaling D of chromatin domains was elevated in tumor cells, histologically normal-appearing cells 4 cm proximal to the tumor, and histologically normal-appearing rectal mucosa compared to cells from control patients (p<0.001). Nuclear D had a robust correlation with the model of 5-year risk of CRC with r2=0.94. Furthermore, rectal D was evaluated as a screening biomarker for patients with advanced adenomas presenting an AUC of 0.85 and 85% sensitivity and specificity. Artificial Intelligence (AI)-enhanced csPWS improved diagnostic performance with AUC=0.90. Considering the low sensitivity of existing CRC tests, including liquid biopsies, to early-stage cancers our work highlights the potential of chromatin biomarkers of field carcinogenesis in detecting early, significant precancerous colon lesions.

Early screening of colorectal cancer using feature engineering with artificial intelligence-enhanced analysis of nanoscale chromatin modifications.

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7-8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5-20 nm, ~ 1 kbp) fold into chromatin packing domains (~ 100-200 nm, ~ 100-1,000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity of cancer cells. We deployed an optical spectroscopic nanosensing technique, chromatin-sensitive partial wave spectroscopic microscopy (csPWS), to evaluate the packing density scaling D of the chromatin chain conformation within packing domains from rectal mucosa in 256 patients with varying degrees of progression to colorectal cancer. We found average packing scaling D of chromatin domains was elevated in tumor cells, histologically normal-appearing cells 4 cm proximal to the tumor, and histologically normal-appearing rectal mucosa compared to cells from control patients (p < 0.001). Nuclear D had a robust correlation with the model of 5-year risk of CRC with r2 = 0.94. Furthermore, rectal D was evaluated as a screening biomarker for patients with advanced adenomas presenting an AUC of 0.85 and 85% sensitivity and specificity. Artificial Intelligence (AI)-enhanced csPWS improved diagnostic performance with AUC = 0.90. Considering the low sensitivity of existing CRC tests, including liquid biopsies, to early-stage cancers our work highlights the potential of chromatin biomarkers of field carcinogenesis in detecting early, significant precancerous colon lesions.

Clinical Profile and Outcomes of Rheumatic Heart Disease Patients Undergoing Surgical Valve Procedures in Uganda.

Background: Chronic valvular heart disease is a well-known, long-term complication of acute rheumatic fever (ARF), which remains a major public health problem in low- and middle-income countries. Access to surgical management remains limited. Outcomes of the minority proportion of patients that access surgery have not been described in Uganda. Objectives: To describe the volume and type of rheumatic heart disease (RHD) valvular interventions and the outcomes of operated patients in the Uganda RHD registry. Methods: We performed a retrospective cohort study of all valve surgery procedures identified in the Uganda RHD registry through December 2021. Results: Three hundred and sixty-seven surgical procedures were performed among 359 patients. More than half were among young (55.9% were ≤20 years of age), female (59.9%) patients. All patients were censored at 15 years. The median (IQR) follow up period was 43 (22,79) months. Nearly half of surgeries (46.9%) included interventions on multiple valves, and most valvular operations were replacements with mechanical prostheses (96.6%). Over 70% of the procedures were sponsored by charity organizations. The overall mortality of patients who underwent surgery was 13% (47/359), with over half of the mortalities occurring within the first year following surgery (27/47; 57.4%). Fifteen-year survival or freedom from re-operation was not significantly different between those receiving valve replacements and those receiving valve repair (log-rank p = 0.76). Conclusions: There has been increasing access to valve surgery among Ugandan patients with RHD. Post-operative survival is similar to regionally reported rates. The growing cohort of patients living with prosthetic valves necessitates national expansion and decentralization of post-operative care services. Major reliance on charity funding of surgery is unsustainable, thus calling for locally generated and controlled support mechanisms such as a national health insurance scheme. The central illustration (Figure 1) provides a summary of our findings and recommendations.

Epidemiology of Postoperative Complications After Esophagectomy: Implications for Management.

BACKGROUND: Despite advances in operative techniques and postoperative care, esophagectomy remains a morbid operation. Leveraging complication epidemiology and the correlation of these complications may improve rescue and refine early recovery pathways. METHODS: This study retrospectively reviewed all esophagectomies performed at a tertiary academic center from 2014 to 2021 and quantified the timing of the most common complications. Daily incidence values for index complications were calculated, and a covariance matrix was created to examine the correlation of the complications with each other. Study investigators performed a Cox proportional hazards analysis to clarify the association between early diagnosis of postoperative atrial fibrillation and pneumonia with subsequent anastomotic leak. RESULTS: The study analyzed 621 esophagectomies, with 580 (93.4%) cervical anastomoses and 474 (76%) patients experiencing complications. A total of 159 (25.6%) patients had postoperative atrial fibrillation, and 155 (25.0%) had an anastomotic leak. The median (interquartile range [IQR]) postoperative day of these complications was day 2 (IQR, days 2-3) and day 8 (IQR, days 7-11), respectively. Our covariance matrix found significant associations in the variance of the most common postoperative complications, including pneumonia, atrial fibrillation, anastomotic leak, and readmissions. Early postoperative atrial fibrillation (hazard ratio, 8.1; 95% CI, 5.65-11.65) and postoperative pneumonia (hazard ratio, 3.8; 95% CI, 1.98-7.38) were associated with anastomotic leak. CONCLUSIONS: Maintaining a high index of suspicion for early postoperative complications is crucial for rescuing patients after esophagectomy. Early postoperative pneumonia and atrial fibrillation may be sentinel complications for an anastomotic leak, and their occurrence may be used to prompt further clinical investigation. Early recovery protocols should consider the development of early complications into postoperative feeding and imaging algorithms.

Early detection of lung cancer using artificial intelligence-enhanced optical nanosensing of chromatin alterations in field carcinogenesis.

Supranucleosomal chromatin structure, including chromatin domain conformation, is involved in the regulation of gene expression and its dysregulation has been associated with carcinogenesis. Prior studies have shown that cells in the buccal mucosa carry a molecular signature of lung cancer among the cigarette-smoking population, the phenomenon known as field carcinogenesis or field of injury. Thus, we hypothesized that chromatin structural changes in buccal mucosa can be predictive of lung cancer. However, the small size of the chromatin chain (approximately 20 nm) folded into chromatin packing domains, themselves typically below 300 nm in diameter, preclude the detection of alterations in intradomain chromatin conformation using diffraction-limited optical microscopy. In this study, we developed an optical spectroscopic statistical nanosensing technique to detect chromatin packing domain changes in buccal mucosa as a lung cancer biomarker: chromatin-sensitive partial wave spectroscopic microscopy (csPWS). Artificial intelligence (AI) was applied to csPWS measurements of chromatin alterations to enhance diagnostic performance. Our AI-enhanced buccal csPWS nanocytology of 179 patients at two clinical sites distinguished Stage-I lung cancer versus cancer-free controls with an area under the ROC curve (AUC) of 0.92 ± 0.06 for Site 1 (in-state location) and 0.82 ± 0.11 for Site 2 (out-of-state location).

Dexamethasone intravitreal implant in diabetic macular oedema refractory to anti-vascular endothelial growth factors: the AUSSIEDEX study.

AIM: To evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: This prospective, open-label, observational, real-world study included pseudophakic and phakic (scheduled for cataract surgery) eyes that did not achieve a ≥5-letter best corrected visual acuity (BCVA) gain and/or clinically significant central subfield retinal thickness (CRT) improvement after 3-6 anti-VEGF injections for DME (N=143 eyes), regardless of baseline BCVA and CRT. After an initial DEX injection (baseline visit), reinjection was permitted at ≥16-week intervals. PRIMARY ENDPOINTS: changes in mean BCVA and CRT from baseline to week 52. Safety assessments included adverse events. RESULTS: Of 143 eyes, 53 (37.1%) and 89 (62.2%) switched to DEX after 3-6 (early) and >6 (late) anti-VEGF injections, respectively; 1 (0.7%) had missing information. With 2.3 injections (mean) over 52 weeks, the change in mean BCVA from a baseline of 57.8 letters was not significant at week 52. Mean CRT improved significantly from a baseline of 417.8 µm at week 52 (mean change -60.9 µm; p<0.001). Outcomes were similar in eyes switched to DEX early and late. No unexpected adverse events were reported; no filtration surgeries were required. CONCLUSION: To date, AUSSIEDEX is the largest prospective, real-world study of DEX monotherapy for treatment-naïve or anti-VEGF-refractory DME. Following early or late switch from anti-VEGF agents, DEX significantly improved anatomic outcomes at 52 weeks without new safety concerns, supporting use in anti-VEGF-refractory DME. TRIAL REGISTRATION NUMBER: NCT02731911.

Evidence-based opioid prescribing guidelines after lung resection: a prospective, multicenter analysis.

Background: Opioid prescribing guidelines have significantly decreased overprescribing and post-discharge use after cardiac surgery; however, limited recommendations exist for general thoracic surgery patients, a similarly high-risk population. We examined opioid prescribing and patient-reported use to develop evidence-based, opioid prescribing guidelines after lung cancer resection. Methods: This prospective, statewide, quality improvement study was conducted between January 2020 to March 2021 and included patients undergoing surgical resection of a primary lung cancer across 11 institutions. Patient-reported outcomes at 1-month follow-up were linked with clinical data and Society of Thoracic Surgery (STS) database records to characterize prescribing patterns and post-discharge use. The primary outcome was quantity of opioid used after discharge; secondary outcomes included quantity of opioid prescribed at discharge and patient-reported pain scores. Opioid quantities are reported in number of 5-mg oxycodone tablets (mean ± standard deviation). Results: Of the 602 patients identified, 429 met inclusion criteria. Questionnaire response rate was 65.0%. At discharge, 83.4% of patients were provided a prescription for opioids of mean size 20.5±13.1 pills, while patients reported using 8.2±13.0 pills after discharge (P<0.001), including 43.7% who used none. Those not taking opioids on the calendar day prior to discharge (32.4%) used fewer pills (4.4±8.1 vs. 11.7±14.9, P<0.001). Refill rate was 21.5% for patients provided a prescription at discharge, while 12.5% of patients not prescribed opioids at discharge required a new prescription before follow-up. Pain scores were 2.4±2.5 for incision site and 3.0±2.8 for overall pain (scale 0-10). Conclusions: Patient-reported post-discharge opioid use, surgical approach, and in-hospital opioid use before discharge should be used to inform prescribing recommendations after lung resection.

Salvage Cryoablation for Recurrent Prostate Cancer Following Primary External Beam Radiotherapy or Primary Cryotherapy: A Propensity Score Matched Analysis of Mid-term Oncologic and Functional Outcomes.

INTRODUCTION: Local prostate cancer recurrence following radiotherapy (XRT) or cryoablation (CRYO) may be addressed with salvage cryotherapy (SCT), although little is known about how the primary treatment modality affects SCT results. Oncologic and functional outcomes of patients who underwent SCT after primary XRT (XRT-SCT) or cryoablation (CRYO-SCT) were studied. METHODS: Data was collected using the Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression-free survival (BPFS).  Urinary incontinence, rectourethral fistula, and erectile dysfunction were secondary outcomes. The Kaplan-Meier log-rank test and univariable/multivariable Cox proportional hazards (CPH) models were utilized to evaluate BPFS between groups. RESULTS: 419 XRT-SCT and 63 CRYO-SCT patients met inclusion criteria, that was reduced to 63 patients in each cohort after propensity matching. There was no difference in BPFS at 2 and 5 years both before (P = .5 and P = .7) and after matching (P = .6 and P = .3). On multivariable CPH, BPFS was comparable between treatment groups (CRYO-SCT, HR=1.1, [0.2-2.2]).  On the same analysis, BPFS was lower in D'Amico high-risk (HR 3.2, P < .01) and intermediate-risk (HR 1.95, P < .05) categories compared to low-risk. There was no significant difference in functional outcomes between cohorts. CONCLUSION: Following primary cryotherapy, salvage cryoablation provides comparable intermediate oncological outcomes and functional outcomes compared to primary radiotherapy.