Performance Status and End-of-Life Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Androgen Receptor Targeted Therapy.

OBJECTIVES: Androgen receptor targeted therapies (ARTs) are widely preferred over taxane chemotherapy due to their good tolerability and similar efficacy. However, there is a paucity of data that support the use of ART therapy or describe end-of-life (EOL) outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) with reduced performance status (PS) (European Cooperative Oncology Group [ECOG] ≥2). METHODS: We performed a retrospective, single-institution study of 142 patients with mCRPC who received ART therapy between 2010 and 2021. We assessed each record for baseline demographic and clinical information, ART treatment course, and survival and EOL outcomes. Our primary aim was to compare overall survival (OS) between the two groups (ECOG ≥2 vs 0 to 1), and our secondary aim was to describe EOL outcomes. Fisher exact tests and Wilcoxon signed-rank tests were used to compare baseline characteristics. Cox regression was used to compare OS for patients with ECOG ≥2 at the start of treatment with those who had an ECOG of 0 or 1. Descriptive analyses were performed to assess EOL outcomes between the groups. RESULTS: Patients with mCRPC and decreased PS experienced shorter OS on ART compared with those with higher PS. Moreover, when examining EOL outcomes, a near majority of these patients died in the hospital, with a greater percentage among those with an ECOG ≥2. CONCLUSION: These findings highlight the need for continual assessment of PS, improved shared decision-making in ART treatment, and additional research exploring the association between PS and EOL outcomes.

Subglottic dilatation in extremely preterm infants on prolonged mechanical ventilation.

BACKGROUND: Airway injuries are reported among preterm infants with bronchopulmonary dysplasia. We hypothesized that prolonged ventilation in preterm infants is associated with subglottic dilatation that can be reliably evaluated by point of care ultrasonography (POCUS). METHODS: All preterm infants (<29-weeks) admitted to the neonatal ICU at the Advent-Health from January-2020 to June-2022 were eligible if they required invasive ventilation for ≤7 days in the first 28 days of life (control) or remained intubated for ≥28 days (prolonged ventilation). Sonography was performed by one technician and all images were reviewed by the pediatric radiologist. The trachea size was measured 3 times by randomly selecting three images. The first 20 scans were also independently reported by a different pediatric radiologist. Intra and inter-observer variability was estimated. Mean trachea size and weight at the time of imaging were compared. RESULTS: Out of 417 eligible infants; 11 died before 28 days and 163 required ventilation for 8-27 days. Consent missed for 80 infants during COVID-19 pandemic. We enrolled 23 and 28 infants in the control & prolonged ventilation groups, respectively. Inter and intra-observer correlations were 0.83 and 0.97 respectively. Infants in the control group had higher gestation and birth weight. Infants on prolonged ventilation were at higher risk for infections, BPD, longer hospital stay and significant subglottic dilation (4.51 ± 0.04 vs 4.17 ± 0.02 mm, p < 0.01) despite smaller body weight at the time of imaging (884 ± 102 vs 1059 ± 123g, p < 0.01). CONCLUSION: Extremely preterm infants on prolonged ventilation are at risk for sub-glottic dilatation that can be reliably measured by POCUS.

Optimizing Clinical Trial Eligibility Design Using Natural Language Processing Models and Real-World Data: Algorithm Development and Validation.

BACKGROUND: Clinical trials are vital for developing new therapies but can also delay drug development. Efficient trial data management, optimized trial protocol, and accurate patient identification are critical for reducing trial timelines. Natural language processing (NLP) has the potential to achieve these objectives. OBJECTIVE: This study aims to assess the feasibility of using data-driven approaches to optimize clinical trial protocol design and identify eligible patients. This involves creating a comprehensive eligibility criteria knowledge base integrated within electronic health records using deep learning-based NLP techniques. METHODS: We obtained data of 3281 industry-sponsored phase 2 or 3 interventional clinical trials recruiting patients with non-small cell lung cancer, prostate cancer, breast cancer, multiple myeloma, ulcerative colitis, and Crohn disease from ClinicalTrials.gov, spanning the period between 2013 and 2020. A customized bidirectional long short-term memory- and conditional random field-based NLP pipeline was used to extract all eligibility criteria attributes and convert hypernym concepts into computable hyponyms along with their corresponding values. To illustrate the simulation of clinical trial design for optimization purposes, we selected a subset of patients with non-small cell lung cancer (n=2775), curated from the Mount Sinai Health System, as a pilot study. RESULTS: We manually annotated the clinical trial eligibility corpus (485/3281, 14.78% trials) and constructed an eligibility criteria-specific ontology. Our customized NLP pipeline, developed based on the eligibility criteria-specific ontology that we created through manual annotation, achieved high precision (0.91, range 0.67-1.00) and recall (0.79, range 0.50-1) scores, as well as a high F1-score (0.83, range 0.67-1), enabling the efficient extraction of granular criteria entities and relevant attributes from 3281 clinical trials. A standardized eligibility criteria knowledge base, compatible with electronic health records, was developed by transforming hypernym concepts into machine-interpretable hyponyms along with their corresponding values. In addition, an interface prototype demonstrated the practicality of leveraging real-world data for optimizing clinical trial protocols and identifying eligible patients. CONCLUSIONS: Our customized NLP pipeline successfully generated a standardized eligibility criteria knowledge base by transforming hypernym criteria into machine-readable hyponyms along with their corresponding values. A prototype interface integrating real-world patient information allows us to assess the impact of each eligibility criterion on the number of patients eligible for the trial. Leveraging NLP and real-world data in a data-driven approach holds promise for streamlining the overall clinical trial process, optimizing processes, and improving efficiency in patient identification.

Maternal recorded voice played to preterm infants in incubators reduces her own depression, anxiety and stress: a pilot randomized control trial.

OBJECTIVE: To study the effects of playing mother's recorded voice to preterm infants in the NICU on their mothers' mental health as measured by the Depression, Anxiety and Stress Scale -21 (DASS-21) questionnaire. DESIGN/METHODS: This was a pilot single center prospective randomized controlled trial done at a level IV NICU. The trial was registered at clinicaltrials.gov (NCT04559620). Inclusion criteria were mothers of preterm infants with gestational ages between 26wks and 30 weeks. DASS-21 questionnaire was administered to all the enrolled mothers in the first week after birth followed by recording of their voice by the music therapists. In the interventional group, recorded maternal voice was played into the infant incubator between 15 and 21 days of life. A second DASS-21 was administered between 21 and 23 days of life. The Wilcoxon rank-sum test was used to compare DASS-21 scores between the two groups and Wilcoxon signed-rank test was used to compare the pre- and post-intervention DASS-21 scores. RESULTS: Forty eligible mothers were randomized: 20 to the intervention group and 20 to the control group. The baseline maternal and neonatal characteristics were similar between the two groups. There was no significant difference in the DASS-21 scores between the two groups at baseline or after the study intervention. There was no difference in the pre- and post-interventional DASS-21 scores or its individual components in the experimental group. There was a significant decrease in the total DASS-21 score and the anxiety component of DASS-21 between weeks 1 and 4 in the control group. CONCLUSION: In this pilot randomized control study, recorded maternal voice played into preterm infant's incubator did not have any effect on maternal mental health as measured by the DASS-21 questionnaire. Data obtained in this pilot study are useful in future RCTs (Randomized Controlled Trial) to address this important issue.

Single-cell transcriptomic-informed deconvolution of bulk data identifies immune checkpoint blockade resistance in urothelial cancer.

Interactions within the tumor microenvironment (TME) significantly influence tumor progression and treatment responses. While single-cell RNA sequencing (scRNA-seq) and spatial genomics facilitate TME exploration, many clinical cohorts are assessed at the bulk tissue level. Integrating scRNA-seq and bulk tissue RNA-seq data through computational deconvolution is essential for obtaining clinically relevant insights. Our method, ProM, enables the examination of major and minor cell types. Through evaluation against existing methods using paired single-cell and bulk RNA sequencing of human urothelial cancer (UC) samples, ProM demonstrates superiority. Application to UC cohorts treated with immune checkpoint inhibitors reveals pre-treatment cellular features associated with poor outcomes, such as elevated SPP1 expression in macrophage/monocytes (MM). Our deconvolution method and paired single-cell and bulk tissue RNA-seq dataset contribute novel insights into TME heterogeneity and resistance to immune checkpoint blockade.

Prostate Cancer Foundation Screening Guidelines for Black Men in the United States.

BACKGROUND: In the United States, Black men are at highest risk for being diagnosed with and dying from prostate cancer. Given this disparity, we examined relevant data to establish clinical prostate-specific antigen (PSA) screening guidelines for Black men in the United States. METHODS: A comprehensive literature search identified 1848 unique publications for screening. Of those screened, 287 studies were selected for full-text review, and 264 were considered relevant and form the basis for these guidelines. The numbers were reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: Three randomized controlled trials provided Level 1 evidence that regular PSA screening of men 50 to 74 years of age of average risk reduced metastasis and prostate cancer death at 16 to 22 years of follow-up. The best available evidence specifically for Black men comes from observational and modeling studies that consider age to obtain a baseline PSA, frequency of testing, and age when screening should end. Cohort studies suggest that discussions about baseline PSA testing between Black men and their clinicians should begin in the early 40s, and data from modeling studies indicate prostate cancer develops 3 to 9 years earlier in Black men compared with non-Black men. Lowering the age for baseline PSA testing to 40 to 45 years of age from 50 to 55 years of age, followed by regular screening until 70 years of age (informed by PSA values and health factors), could reduce prostate cancer mortality in Black men (approximately 30% relative risk reduction) without substantially increasing overdiagnosis. CONCLUSIONS: These guidelines recommend that Black men should obtain information about PSA screening for prostate cancer. Among Black men who elect screening, baseline PSA testing should occur between ages 40 and 45. Depending on PSA value and health status, annual screening should be strongly considered. (Supported by the Prostate Cancer Foundation.).

Treatment Patterns and Clinical Outcomes Among Patients With Metastatic Prostate Cancer Harboring Homologous Recombination Repair Mutations.

BACKGROUND: There is currently limited literature assessing the real-world treatment patterns and clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations. METHODS: Medical charts were abstracted for mCRPC patients with ≥ 1 of 12 HRR somatic gene alterations treated at US oncology centers participating in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange. Treatment patterns and clinical outcomes were assessed from the initiation of first-line or later (1L+) mCRPC therapy received on or after July 1, 2014. RESULTS: Among 138 patients included in the study, the most common somatic HRR mutations were CDK12 (47.8%), BRCA2 (22.5%), and ATM (21.0%). Novel hormonal therapy and taxane chemotherapy were most commonly used in 1L; taxane use increased in later lines. Median overall survival (95% confidence interval [CI]) was 36.3 (30.7-47.8) months from initiation of 1L therapy and decreased for subsequent lines. Similarly, there was a trend of decreasing progression-free survival and prostate-specific antigen response from 1L to 4L+ therapy. CONCLUSIONS: Treatment patterns identified in this study were similar to those among patients with mCRPC regardless of tumor HRR mutation status in the literature.

Management of Hemorrhoids and Anal Fissures.

Hemorrhoids and anal fissures are two of the most common benign anorectal diseases. Despite their high prevalence, diagnostic accuracy of benign anorectal disease is suboptimal at 70% for surgeons, especially for hemorrhoidal diseases. Once the diagnosis is correctly made, numerous medical and surgical treatment options are available, each with different rates of success and complications. In this article, the authors review each step of patient management, with emphasis on evidence-based treatment options for hemorrhoids and anal fissures. The article discusses the pathophysiology, diagnosis, medical management, and procedures for hemorrhoids followed by a detailed overview on the management of anal fissures.

Higher fluid and lower caloric intakes: associated risk of severe bronchopulmonary dysplasia in ELBW infants.

OBJECTIVE: To examine nutritional intake profiles and growth trajectories of extremely low birth weight (ELBW) infants who develop severe bronchopulmonary dysplasia (BPD). STUDY DESIGN: Case-control study using multiple logistic regression analysis with generalized estimating equations (GEE) to adjust for matching. RESULTS: Cumulative and mean fluid intakes were higher (p = 0.003) and caloric intakes lower (p < 0.0001) through week two in infants who developed severe BPD (n = 120) versus those without severe BPD (n = 104). Mean caloric intake through week 12 was lower in infants who developed severe BPD (102 ± 10.1 vs. 107 ± 8.5 kcal/kg/day, p < 0.0001). In the logistic regression models, lower mean caloric intake through week 12 was associated with increased risk of developing severe BPD. Linear growth reduced the odds of BPD by ~30% for each Z-score point. CONCLUSIONS: Higher fluid and lower total caloric intakes and reductions in linear growth were independently associated with an increased risk of developing severe BPD in ELBW infants.

Risk Factors for Early Treatment Discontinuation Due to Toxicity Among Patients With Metastatic Castration-resistant Prostate Cancer Receiving Androgen Receptor-targeted Therapy.

OBJECTIVES: Androgen receptor-targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including treatment-related toxicity. We aim to describe reasons for ART treatment discontinuation and identify predictors associated with increased risk of treatment discontinuation due to toxicity. METHODS: We performed a single-institution retrospective review of patients with mCRPC receiving ART between 2010 and 2021. Our primary aim was to identify risk factors for treatment discontinuation due to toxicity. Our secondary aim was to describe ART discontinuation patterns among patients with mCRPC. RESULTS: One hundred thirty-three patients with mCRPC started and discontinued ARTs. Fourteen patients (10.5%) discontinued treatment due to toxicity. Common reasons for treatment discontinuation include Prostate Specific Antigen test progression, radiographic progression, toxicity, and death. Significant predictors of treatment discontinuation due to toxicity on bivariate analysis and multivariate analysis included patient-reported falls (odds ratio [OR]: 7.67, CI: [1.31-40.42]; P =0.016), rash (OR: 13.4, CI: [1.35-134.81]; P =0.026), and weakness (OR: 4.16, CI: [1.15-15.0]; P =0.019). CONCLUSIONS: Our work presents the first description of ART treatment discontinuation and its causes in the real-world setting, as well as patient-reported side effects. Most patients with mCRPC discontinued treatment due to the progression of disease and a minority of patients discontinued secondary to treatment toxicity. Initial multivariable analysis suggests that patient-reported weakness, falls, and rash were associated with a higher likelihood of treatment discontinuation due to toxicity. Early monitoring of this population can prolong the duration of treatment and prevent unnecessary treatment burden.

Analysis of real-world data to investigate evolving treatment sequencing patterns in advanced non-small cell lung cancers and their impact on survival.

Background: Although optimal sequencing of systemic therapy in cancer care is critical to achieving maximal clinical benefit, there is a lack of analysis of treatment sequencing in advanced non-small cell lung cancer (aNSCLC) in real-world settings. Methods: A retrospective cohort study of 13,340 lung cancer patients within the Mount Sinai Health System (MSHS) was performed. Systemic therapy data of aNSCLC in 2,106 patients was the starting point in our analysis to investigate how treatment sequencing has evolved, the impact of sequencing patterns on clinical outcomes, and the effectiveness of 2nd line chemotherapy after patients progressed on immune checkpoint inhibitor (ICI)-based therapy as the 1st line of therapy (LOT). Results: There is a significant shift to more ICI-based therapy and multiple lines of targeted therapy after 2015. We compared clinical outcomes of two patient populations with different treatment sequencing patterns, with the 1st group receiving chemotherapy as the 1st LOT followed by ICI-based treatment, and the 2nd group treated in the opposite order receiving a 1st line ICI-containing regimen followed by a 2nd line chemotherapy. No statistically significant difference in overall survival (OS) was observed between the two groups [group 2 vs. group 1, adjusted hazard ratio (aHR) =1.36, P=0.39]. We assessed the efficacy of the 2nd line chemotherapy in three patient populations given either 1st line ICI single agent, 1st line ICI-chemotherapy combination, or 1st line chemotherapy alone, there was no statistically significant difference in time-to-next treatment (TTNT) and in OS among the three patient groups. Conclusions: Analysis of real-world data has shown two treatment sequencing patterns in aNSCLC, ICI followed by chemotherapy or chemotherapy followed by ICI, achieved similar clinical benefit. The chemotherapies routinely used following platinum doublet 1st LOT, is effective as the 2nd line option after ICI-chemotherapy combination in the 1st line setting.

Routine versus no assessment of gastric residual volumes in preterm infants receiving enteral feeding via intermittent feeding tubes: a randomized controlled trial.

OBJECTIVE: To evaluate whether eliminating routine gastric residual volume (GRV) assessments would lead to quicker attainment of full feeding volumes in preterm infants. STUDY DESIGN: This is a prospective randomized controlled trial of infants ≤32 weeks gestation and birthweight ≤1250 g admitted to a tertiary care NICU. Infants were randomized to assess or not assess GRV before enteral tube feedings. The primary outcome was time to attain full enteral feeding volume defined as 120 ml/kg/day. The Wilcoxon rank sum test was used to compare the days to reach full enteral feeds between the two groups. RESULTS: 80 infants were randomized, 39 to the GRV assessing and 41 to the No-GRV assessing group. A predetermined interim analysis at 50% enrollment showed no difference in primary outcome and the study was stopped as recommended by the Data Safety Monitoring Committee. There was no significant difference in median days to reach full enteral feeds between the two groups [GRV assessment: 12d (5) vs. No-GRV assessment:13d (9)]. There was no mortality in either group, one infant in each group developed necrotizing enterocolitis stage 2 or greater. CONCLUSION: Eliminating the practice of gastric residual volume assessment before feeding did not result in shorter time to attain full feeding.

Antenatal Steroids, Prophylactic Indomethacin, and the Risk of Spontaneous Intestinal Perforation.

OBJECTIVE: To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1). STUDY DESIGN: A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 220-286 weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI. RESULTS: Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (P = .10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P < .0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P = .7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003). CONCLUSION: The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP.

Biomarker Development Trial of Satraplatin in Patients with Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer (mCRPC). Repeat biopsies are uncommon in mCRPC, limiting the feasibility of tissue-based biomarkers. This phase II study sought to evaluate the feasibility and utility of blood-based biomarkers to identify platinum-sensitive mCRPC. METHODS: Patients with mCRPC who had progressed on docetaxel were enrolled at a single center from 2011 to 2013. Subjects received satraplatin 80 mg/m2 by mouth daily on days 1-5 and prednisone 5 mg PO twice daily, on a 35-day cycle. Serial peripheral blood samples were collected for biomarker assessment. RESULTS: Thirteen docetaxel-refractory mCRPC patients were enrolled, with a median age of 69 years (range 54-77 years) and median PSA of 71.7 ng/mL (range 0.04-3057). Four of 13 patients (31%) responded to satraplatin (defined as a PSA decline of ≥30%). Responders demonstrated improved time to disease progression (206 vs. 35 days, HR 0.26, 95% CI, 0.02-0.24, P = .003). A 6-gene peripheral blood RNA signature and serum tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were assessed as biomarkers, but neither was significantly associated with response to satraplatin. CONCLUSION: In this small series, one-third of mCRPC patients responded to platinum-based chemotherapy. Peripheral blood biomarker measurement is feasible in mCRPC, though the biomarkers we investigated were not associated with platinum response. Other biomarkers, such as DNA damage repair mutations, should be evaluated.

Effect of concurrent beta-blocker use in patients receiving immune checkpoint inhibitors for advanced solid tumors.

PURPOSE: Stress-induced adrenergic signaling can suppress the immune system. In animal models, pharmacological beta-blockade stimulates CD8 + T-cell activity and improves clinical activity of immune checkpoint blockade (ICB) in inhibiting tumor growth. Herein, we investigated the effect of BB on clinical outcomes of patients receiving ICB in advanced solid tumors. METHODS: We retrospectively evaluated patients with solid tumors treated with ICB at our institution from January 1, 2011 to April 28, 2017. The primary clinical outcome was disease control. Secondary clinical outcomes were overall survival (OS), and duration of therapy (DoT). The primary predictor was use of BB. Association between disease control status and BB use was assessed in univariable and multivariable logistic regression. OS was calculated using hazard ratios of BB-recipient patients vs. BB non-recipient patients via Cox proportional hazards regression models. All tests were two-sided at a significance level of 0.05. RESULTS: Of 339 identified patients receiving ICB, 109 (32%) also received BB. In covariate-adjusted analysis, odds of disease control were significantly higher among BB recipients compared to BB-non-recipients (2.79; [1.54-5.03]; P = 0.001). While we did not observe significant association of OS with the use of BB overall, significant association with better OS was observed for the urothelial carcinoma cohort (HR: 0.24; [0.09, 0.62]; P = 0.0031). CONCLUSIONS: Concurrent use of BB may enhance the clinical activity of ICB and influence overall survival, particularly in patients with urothelial carcinoma. Our findings warrant further investigation to understand the interaction of beta adrenergic signaling and antitumor immune activity and explore a combination strategy.

Fluid Intake in the First Week of Life and the Duration of Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants.

OBJECTIVE: This study aimed to determine the association between daily fluid intake and the duration of hemodynamically significant patent ductus arteriosus (hsPDA). STUDY DESIGN: This is a retrospective cohort study of extremely preterm infants (<29 weeks) admitted in the Neonatal Intensive Care Unit of the Advent Health for Children from January 2013 to March 2016, if hsPDA was diagnosed in first week of life and serial echocardiograms were available. Diagnosis of hsPDA was based on a scoring system and its duration was estimated from serial echocardiograms. Cohort was divided into two groups based on duration of hsPDA (<1week, group A and ≥1 week, group B). Daily fluid intake was categorized as prescribed and actual. Prescribed volume was ordered by clinicians based on birth weight, not including trophic feeds, intravenous (IV) boluses or transfusions, etc. Actual intake was calculated by the electronic medical records based on daily weights and included all enteral or parenteral fluids. Multivariate analysis was performed to determine an association between total daily fluid intake over the first week of life and the duration of hsPDA. Two groups were compared to observe the difference between prescribed and actual daily fluid intakes. RESULTS: We enrolled 50 infants in group A and 76 in group B. Infants in group B were of significantly lower gestation and required prolonged ventilation and hospitalization. An association between higher fluid intake in the first 2 days of life and prolonged duration of hsPDA was confirmed by multivariate analysis. Actual fluid intake was significantly higher than prescribed total fluid intake in first 4 days of life for infants in both groups. CONCLUSION: In extremely preterm infants, higher fluid intake in first 2 days of life is associated with prolonged duration of hsPDA. Actual daily fluid intake can be significantly higher than prescribed daily fluids due to daily weight changes and additional fluid administration. KEY POINTS: · In preterm infants, actual daily fluid intake may be higher than prescribed volume.. · Higher daily fluid intake in first week of life is associated with prolonged duration of PDA.. · PDA scoring system can be helpful for objective assessment of PDA in preterm infants..

Detecting Ground Glass Opacity Features in Patients With Lung Cancer: Automated Extraction and Longitudinal Analysis via Deep Learning-Based Natural Language Processing.

BACKGROUND: Ground-glass opacities (GGOs) appearing in computed tomography (CT) scans may indicate potential lung malignancy. Proper management of GGOs based on their features can prevent the development of lung cancer. Electronic health records are rich sources of information on GGO nodules and their granular features, but most of the valuable information is embedded in unstructured clinical notes. OBJECTIVE: We aimed to develop, test, and validate a deep learning-based natural language processing (NLP) tool that automatically extracts GGO features to inform the longitudinal trajectory of GGO status from large-scale radiology notes. METHODS: We developed a bidirectional long short-term memory with a conditional random field-based deep-learning NLP pipeline to extract GGO and granular features of GGO retrospectively from radiology notes of 13,216 lung cancer patients. We evaluated the pipeline with quality assessments and analyzed cohort characterization of the distribution of nodule features longitudinally to assess changes in size and solidity over time. RESULTS: Our NLP pipeline built on the GGO ontology we developed achieved between 95% and 100% precision, 89% and 100% recall, and 92% and 100% F1-scores on different GGO features. We deployed this GGO NLP model to extract and structure comprehensive characteristics of GGOs from 29,496 radiology notes of 4521 lung cancer patients. Longitudinal analysis revealed that size increased in 16.8% (240/1424) of patients, decreased in 14.6% (208/1424), and remained unchanged in 68.5% (976/1424) in their last note compared to the first note. Among 1127 patients who had longitudinal radiology notes of GGO status, 815 (72.3%) were reported to have stable status, and 259 (23%) had increased/progressed status in the subsequent notes. CONCLUSIONS: Our deep learning-based NLP pipeline can automatically extract granular GGO features at scale from electronic health records when this information is documented in radiology notes and help inform the natural history of GGO. This will open the way for a new paradigm in lung cancer prevention and early detection.

Effects of lipid emulsions on unbound bilirubin and response to phototherapy in preterm infants.

OBJECTIVE: Bilirubin-induced neurotoxicity is mediated by the fraction of total serum bilirubin (TSB) not bound to albumin (Bf). Unbound free fatty acids (FFAu) generated from lipid emulsions compete with bilirubin for albumin binding, increasing Bf. Soy-based (IL) and soy-MCT-olive-fish oil-based (SMOF) lipid emulsions contain different fatty acids with distinct albumin binding affinities. IL increases Bf in preterm infants, but the effects of SMOF on Bf are not known. Our objective was to compare changes in TSB, Bf, FFAu, and response to phototherapy in preterm infants receiving SMOF and IL. We hypothesized that SMOF would be associated with lower Bf and better response to phototherapy than IL. METHODS: Very preterm and low birth weight infants (<1500 g, <32 weeks) were infused with IL (n = 20) or SMOF (n = 20) as prescribed by providers. Phototherapy was prescribed using the standard care practice. FFAu profiles and levels, TSB, and Bf were measured on 0, 1, 2, and 3 g/kg/day of lipid infusion and at the initiation and termination of phototherapy. TSB was analyzed in the clinical laboratory using the diazo technique. FFAu and Bf were measured using fluorescent probes. RESULTS: Escalating doses of IL and SMOF increased FFAu levels and Bf, but not TSB. Phototherapy did not significantly decrease Bf for infants receiving either lipid. IL-treated infants had higher levels of unbound linoleic acid, and SMOF-treated infants had higher unbound arachidonic, oleic, and docosahexaenoic acids. CONCLUSIONS: IL and SMOF both increase Bf similarly, and phototherapy does not significantly affect Bf for infants receiving them.

Management of de novo metastatic hormone-sensitive prostate cancer: A comprehensive report of a single-center experience.

BACKGROUND: Upfront docetaxel or novel hormonal agents (NHA) such as abiraterone and enzalutamide have become the standard of care for metastatic hormone sensitive prostate cancer (mHSPC). We evaluated real-world management of patients treated with these agents at a single center. PATIENTS AND METHODS: Patients with de novo mHSPC treated with upfront docetaxel or an NHA between January 2014 and April 2019 at Mount Sinai Health System were included. We evaluated time to next treatment (TTNT), PSA progression free survival (PFS) and overall survival (OS) after initial treatment with these drugs. Kaplan Meier method and multivariable Cox proportional hazards models were used for analysis. We additionally assessed the prognostic value of post-treatment PSA. RESULTS: We identified 94 de novo mHSPC patients; 52 and 42 treated with upfront docetaxel and NHAs, respectively. NHAs were associated with a median TTNT of 20.7 months compared to 10.1 months with docetaxel (log-rank p = 0.023). We also observed median PSA PFS of 19 months for NHAs and 13.2 months for docetaxel (p = 0.069). However, OS between the two treatment groups was unchanged. Among docetaxel treated patients, TTNT was shorter among those with high metastasis burden (9.63 vs 25.5 months, p = 0.026) which was not observed among NHA treated patients (25.1 vs 20.7 months, p = 0.79). Regardless of treatment, lower post-treatment PSA levels were associated with improved TTNT (58.95 vs. 11.57 vs. 9.4 months for PSA ≤0.2, 0.2-0.4, >0.4ng/ml, respectively; p<0.001). CONCLUSION: Real world data demonstrated a shorter duration of treatment with docetaxel than NHAs, reflecting the time-limited nature of docetaxel regimens compared to the treat-till-progression approach of NHAs. While TTNT was generally longer for NHAs than docetaxel, some docetaxel-treated patients achieved significant periods of time off treatment. In addition, the depth of PSA response following combination treatment may hold prognostic value for mHSPC outcomes.

Clinical factors associated with outcome in solid tumor patients treated with immune-checkpoint inhibitors: a single institution retrospective analysis.

OBJECTIVES: Response to immune checkpoint inhibitor (ICI) remains limited to a subset of patients and predictive biomarkers of response remains an unmet need, limiting our ability to provide precision medicine. Using real-world data, we aimed to identify potential clinical prognosticators of ICI response in solid tumor patients. METHODS: We conducted a retrospective analysis of all solid tumor patients treated with ICIs at the Mount Sinai Hospital between January 2011 and April 2017. Predictors assessed included demographics, performance status, co-morbidities, family history of cancer, smoking status, cancer type, metastatic pattern, and type of ICI. Outcomes evaluated include progression free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR). Univariable and multivariable Cox proportional hazard models were constructed to test the association of predictors with outcomes. RESULTS: We identified 297 ICI-treated patients with diagnosis of non-small cell lung cancer (N = 81, 27.3%), melanoma (N = 73, 24.6%), hepatocellular carcinoma (N = 51, 17.2%), urothelial carcinoma (N = 51, 17.2%), head and neck squamous cell carcinoma (N = 23, 7.7%), and renal cell carcinoma (N = 18, 6.1%). In multivariable analysis, good performance status of ECOG ≤ 2 (PFS, ORR, DCR and OS) and family history of cancer (ORR and DCR) associated with improved ICI response. Bone metastasis was associated with worse outcomes (PFS, ORR, and DCR). CONCLUSIONS: Mechanisms underlying the clinical predictors of response observed in this real-world analysis, such as genetic variants and bone metastasis-tumor microenvironment, warrant further exploration in larger studies incorporating translational endpoints. Consistently positive clinical correlates may help inform patient stratification when considering ICI therapy.