Factor For Outcome In Patients Research Articles

Vitamin D Deficiency Exacerbates Poor Sleep Outcomes with Endocrine-Disrupting Chemicals Exposure: A Large American Population Study.

Phthalates and bisphenol A are recognized as the predominant endocrine-disrupting substances (EDCs) in the environment, but their impact on sleep health remains unclear. Vitamin D has often been reported to play a role in sleep health and may be affected by endocrine-disrupting compounds. The study utilized data from 5476 individuals in the NHANES project to investigate the correlation between combined exposure to environmental EDCs and sleep duration through modeling various exposures. Furthermore, it emphasizes the importance of vitamin D in the present scenario. Preliminary analyses suggested that vitamin D-deficient individuals generally slept shorter than individuals with normal vitamin D (p < 0.05). Exposure to Mono-ethyl phthalate (MEP), triclosan (TRS), and Mono-benzyl phthalate (MZP), either alone or in combination, was associated with reduced sleep duration and a greater risk of vitamin D deficiency. Individuals with low vitamin D levels exposed to TRS experienced shorter sleep duration than those with normal vitamin D levels (p < 0.05). TRS and MZP were identified as crucial factors in patient outcomes when evaluating mixed exposures (p < 0.05). The results provide new data supporting a link between exposure to EDCs and insufficient sleep length. Additionally, they imply that a vitamin D shortage may worsen the sleep problems induced by EDCs.

Abstract LB104: Tumor fraction as a predictive factor of outcome in patients referred for oncology early phase clinical trials: Analyses of two precision medicine studies

Abstract Modern phase I trials have shown considerable advancement, demonstrating encouraging response rates and subsequently raising the demand for participant enrollment. Despite these advances, there remains a significant challenge: approximately 15% of patients enrolled in these trials pass away within the first 90 days, and nearly half of them do not experience any therapeutic benefit. These statistics underscore the critical need for more effective strategies in selecting suitable patients for trial participation. One promising avenue is the use of circulating tumor DNA (ctDNA) measurements to estimate tumor fraction (TF), a method that has shown potential in prognosticating outcomes for patients with solid tumors. Nevertheless, the effectiveness of TF as an indicator for predicting the clinical benefits of systemic treatments in patients referred for early phase studies is yet to be conclusively determined Methods: We analyzed adult patients with advanced solid tumors included from December 2020 to December 2021 in two precision medicine studies: BIP (NCT02534649) and STING (NCT04932525). Comprehensive genomic profiling was conducted using the FDA approved 324-gene FoundationOne Liquid Cdx assay. TF was categorized as ≥10% or &amp;lt;10%. Multivariate analysis incorporated established prognostic scores (Royal Marsden Hospital: RMH, Garrido-Laguna et al. 2012; and GRIm, Bigot et al., 2017) and their individual components (RMH: albumin, lactate dehydrogenase, number of metastatic sites; GRIm: neutrophil/lymphocyte ratio, lactate dehydrogenase, albumin). Results: A total of 1305 patients referred for early phase trials were evaluated: 871 in BIP and 434 in STING.The treatment regimens patients received post-TF assessment included: cytotoxic agents (BIP: 278 patients, 28.8%; STING: 106 patients, 24.4%), immunotherapy (BIP: 152 patients, 15.8%; STING: 76 patients, 17.5%), tyrosine kinase inhibitors (BIP: 126 patients, 13.1%; STING: 35 patients, 8.1%), hormonal therapy (BIP: 131 patients, 13.6%; STING: 9 patients, 2.1%), and various other therapies or combinations. High TF was significantly correlated with poorer objective response/stable disease rate, shorter progression-free survival (PFS), and lower overall survival (OS) in both studies. Multivariate analysis confirmed TF as an independent predictor of objective response, PFS, and OS, beyond the RMH and GRIm scores and their components. Conclusions: This is the first prospective analysis confirming that TF is a significant predictive marker of treatment efficacy in patients referred for early phase studies. Our findings suggest that TF could be a valuable tool in decision-making for phase I trial participation. Additionally, this research lays the groundwork for future exploration of TF in risk stratification of cancer patients in various clinical contexts. Citation Format: Laila Belcaid, Sophie Cousin, Arnaud Bayle, Melissa Alame, Etienne Rouleau, Laura Blouin, Ludovic Lacroix, Damien Vasseur, Maxime Brunet, Sofiane Taleb, Isabelle Soubeyran, Veronique Debien, Eurydice Angeli, Christophe Massard, Antoine Italiano. Tumor fraction as a predictive factor of outcome in patients referred for oncology early phase clinical trials: Analyses of two precision medicine studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB104.

Abstract 3786: Genomic and transcriptomic characterization of peritoneal, lung and liver metastases of colorectal carcinoma reveals site-specific differences

Abstract Background: Metastasis in colorectal cancer (CRC) is a critical factor in patient outcomes, with 20% of patients affected at the time of diagnosis and up to 50% developing metachronous metastatic disease later on. Despite the growing importance of metastatic sites as independent predictors of overall survival (OS) and the ongoing development of new treatments, there has been limited effort to personalize systemic treatment based on specific metastatic locations. Aim: This study aims to compare the genomic landscape of different metastatic sites in CRC to detect novel diagnostic and therapeutic targets. Methods: DNA whole-genome-sequencing and RNA gene expression data from metastatic CRC samples were retrieved from the Hartwig Medical Foundation (HMF). Single nucleotide variants (SNVs), somatic copy number aberrations (SCNAs) and structural variants (SVs) were reported by HMF with their pipelines. In addition, focal amplifications and deletions were identified using GISTIC2 (v6.15.30). We included 464 microsatellite stable samples derived from liver metastases (n=369), peritoneal metastases (n=58) and lung metastases (n=37). We compared DNA mutation frequencies between tumors from different metastatic sites (two-sided Mann-Whitney tests) and performed differential gene expression and pathway enrichment analysis. Results: Liver metastases had the highest number of focal SCNAs per sample (median 33 vs 17 in peritoneum (p &amp;lt; 0.001); vs 18 in lung (p &amp;lt; 0.001)). Furthermore, we observed 39 site-specific SCNAs in liver, 9 in peritoneal and 15 in lung metastases. Of these, the most significant focal SCNAs were an amplification within 20q13.12 (79%) and deletion within 1p35.3 (64%) in peritoneal metastases and a deletion within 18q21.1 (84%) in lung metastases. Furthermore, peritoneal metastases displayed less genomic instability, featuring lower ploidy (median 2.65 vs 2.94 in liver (p=0.025); vs 3.15 in lung (p=0.025)) and lower aneuploidy scores (median 19 vs 26 in liver (p=0.016); vs 30 in lung (p=0.016)) while having no significant differences in tumor mutational burden or individual SNVs. Analysis of SVs revealed that peritoneal metastases exhibited fewer deletions (≥10kb; 1.3x fold change increase in liver and lung) and fewer duplications (≥1kb; 1.4x fold change increase in liver). Differential gene expression analysis uncovered higher expression of gene sets involved in the apical junction and the TGF-beta-signaling pathway in peritoneal metastases. Conclusion: Specific focal SCNA and differences in genomic instability exhibit an association with preferential organotropism in CRC metastasis and could offer potential targets for the development of new diagnostic and therapeutic approaches. Citation Format: Nerma Crnovrsanin, Soufyan Lakbir, Renske d. Wit, Steven L. Ketelaars, Niels F. Kok, Petur Snaebjornsson, Gerrit A. Meijer, Sanne Abeln, Remond J. Fijneman. Genomic and transcriptomic characterization of peritoneal, lung and liver metastases of colorectal carcinoma reveals site-specific differences [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3786.

Early Peripheral Blood Blast Clearance As a Prognostic Marker for Early Treatment Response in Pediatric Acute Myeloid Leukemia

Background and Significance The cure rate of pediatric acute myeloid leukemia (AML) has improved significantly; however, relapses still occur in up to 30% of the total patient population in high-income countries (HICs), and in an even higher percentage of patients in low- and middle-income countries (LMICs). Early treatment response, cytogenetics and minimal residual disease (MRD) are well-known prognostic factors for treatment outcome; however, sophisticated techniques for identifying prognostic factors are often lacking in LMICs, and are sometimes unsuccessful in HICs. Early treatment response assessed by a bone marrow (BM) aspirate on day 15 or day 22 (D22) (depending on the applicable protocol) after initiation of chemotherapy is a known prognostic factor for outcome in patients with pediatric AML, but does not allow modifications of the first induction chemotherapy course (Creutzig 2014, Abrahamsson 2011, Kern 2003). In both pediatric acute lymphoid leukemia (ALL) and adult AML, early peripheral blood blast clearance (PBBC) is a known early indicator of treatment response (Manabe 2008, Arellano 2012), whereas to the best of our knowledge, this has not yet been reported in pediatric AML. In this study, we evaluated the significance of time to complete PBBC, and rate of PBBC after initiation of chemotherapy, in relation to disease status in BM D22, as measure of early treatment response that has prognostic significance. Study Design and Methods Pediatric patients with AML, aged 0-18 years, that were treated according to the NOPHO-DBH AML-2012 protocol were included. The first 5 days of induction therapy consisted of etoposide, followed by 7 days of low-dose cytarabine and mitoxantrone or liposomal daunorubicin. Peripheral blood (PB) was assessed by morphology at the time of diagnosis, daily in the first week, and thrice weekly until D22 or until occurrence of complete clearance of blasts. BM D22 was assessed by morphology and flow cytometry. A receiver operating characteristic (ROC) analysis was performed to evaluate the predictive power of days from starting chemotherapy to complete PBBC. The correlation between time to complete PBBC and BM D22 results was analyzed using a logistic regression model. Multivariable logistic regression models were applied for the association after adjusting for effects of other covariates. Rate of PBBC was defined as the percentage of the absolute PB blast count on the day of diagnosis that cleared with each day of therapy, on average, until D22 or the day of complete PBBC. Results In total, 319 patients were included, out of whom 241 were eligible for analysis, and 78 not eligible due to missing or incomplete data. Day 9 after initiation of chemotherapy was identified as the most discriminating cut-off point for predicting BM D22 response. Patients were categorized into early PBBC (≤9 days; n=159) and delayed PBBC (&amp;gt;9 days; n=82) groups. Early PBBC was associated with having &amp;lt;5% AML cells in BM D22 as assessed by both morphology (OR 3.11; P=0.005) and flow cytometry (OR 2.73; P=0.041). Early PBBC also showed a much lower likelihood of having &amp;gt;15% AML cells in BM D22 by morphology (OR 0.08; P=0.002). None of the early PBBC patients had &amp;gt;15% AML cells in BM D22 by flow cytometry. For 217 patients (selection due to missing data [n=24]), the rate of PBBC could be calculated, and a discriminative cut-off value of 11% was identified. Patients were categorized into high rate of PBBC (&amp;gt;11%; n=132) and low rate of PBBC (≤11%; n=85). High rate of PBBC was associated with having &amp;lt;5% AML cells in BM D22 by flow cytometry (OR 4.30; P=0.007) and negative MRD status (OR 2.02; P=0.004), while also showing a strong association with a lower likelihood of &amp;gt;15% AML cells in BM D22 (OR 0.11; P=0.007) by morphology. None of the high rate PBBC patients had &amp;gt;15% AML cells in BM D22 by flow cytometry. Conclusion Both early complete PBBC and rate of PBBC after initiation of chemotherapy holds promise as prognostic marker for clinical outcome in pediatric AML, as it correlates significantly with BM D22 response. These findings may offer an early and easily accessible prognostic factor, particularly beneficial for LMICs, as well as for patients with unsuccessful MRD analyses.

Modifiable vascular risk factors for outcomes in patients with CADASIL: A literature review and meta-analysis of cross-sectional analyzes

ObjectiveTo investigate the association between outcomes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and common modifiable vascular risk factors. MethodsStudies published between 1993 and February 2023 from PubMed, Embase, Cochrane, CNKI, and WanFang, along with their references, were systematically examined. Cross-sectional analyzes in patients with CADASIL with information on modifiable cerebrovascular risk factors and outcomes were included. Meta-analysis was conducted if at least three studies were available for each risk factor and outcome. ResultsWe included nine studies and 1687 samples in the analysis. The results of the meta-analysis showed that hypertension was positively associated with stroke in patients with CADASIL (OR = 2.69; 95 % CI: 2.02–3.57). Other vascular risk factors, including diabetes mellitus, dyslipidemia, hyperhomocysteinemia, smoking, alcohol drinking, and obesity, did not show stable correlations between the three outcomes (stroke, dementia, and disability). ConclusionsHypertension was significantly associated with stroke in patients with CADASIL. The role of other vascular risk factors in CADASIL and its outcomes: stroke, dementia, and disability, remains ambiguous.

Impact of body mass index in patients with tricuspid regurgitation after transcatheter edge-to-edge repair

BackgroundObesity and underweight represent classical risk factors for outcome in patients treated for cardiovascular disease. This study describes the impact of different body mass index (BMI) categories on 1-year clinical outcome in patients with tricuspid regurgitation (TR) undergoing transcatheter-edge-to-edge repair (TEER).MethodsWe analyzed 211 consecutive patients (age 78.3 ± 7.2 years, 55.5% female, median EuroSCORE II 9.6 ± 6.7) with tricuspid regurgitation undergoing TEER from June 2015 until May 2021. Patients were prospectively enrolled in our single center registry and were retrospectively analyzed. Patients were stratified according to body mass index (BMI) into 4 groups: BMI < 20 kg/m2 (underweight), BMI 20.0 to < 25.0 kg/m2 (normal weight), BMI 25.0 to > 30.0 kg/m2 (overweight) and BMI ≥ 30 kg/m2 (obese).ResultsKaplan–Meier survival curves demonstrated inferior survival for underweight and obese patients, but comparable outcomes for normal and overweight patients (global log rank test, p < 0.01). Cardiovascular death was significantly higher in underweight patients compared to the other groups (24.1% vs. 7.0% vs. 6.3% vs. 6.4%; p < 0.01). Over all, there were comparable rates of bleeding, stroke and myocardial infarction. Multivariable Cox regression analysis (adjusted for age, gender, coronary artery disease, chronic obstructive pulmonary disease, tricuspid annular plane systolic excursion, left-ventricular ejection fraction) confirmed underweight (HR 3.88; 95% CI 1.64–7.66; p < 0.01) and obesity (HR 3.24; 95% CI 1.37–9.16; p < 0.01) as independent risk factors for 1-year all-cause mortality.ConclusionsCompared to normal weight and overweight patients, obesity and underweight patients undergoing TEER display significant higher 1-year all-cause mortality.Graphical abstract

An analysis of temporal dimensions in maltreatment reporting and child protection responses

BackgroundThe health services literature indicates that the day and time of a medical encounter is often significant factor in patient outcomes, yet little is known about the role of temporal dimensions in child maltreatment reporting or substantiation. ObjectiveWe examined time-specific dynamics of screened-in reports of alleged maltreatment from different reporter sources, including their relationship to the likelihood of substantiation. Participants and settingWe used a population-based dataset of administrative records for 119,758 child protection investigations involving 193,300 unique children in Los Angeles County, California, between 2016 and 2017. MethodsFor each report, we coded three categorical temporal dimensions of the maltreatment report: season, day of the week, and time of day. We descriptively examined how temporal characteristics varied by reporting source. Finally, we ran generalized linear models to estimate the likelihood of substantiation. ResultsWe observed variability overall and by reporter type for all three measures of time. Reports were less likely during summer months (22.2 %), during the weekend (13.6 %), and after midnight (10.4 %). Counts of reports from law enforcement were more common after midnight and contributed to a greater proportion of substantiations over the weekend than other reporter types. Weekend and morning reports were nearly 10 % more likely than weekday and afternoon to be substantiated, respectively. Reporter type was the most prominent factor for substantiation regardless of temporal dimensions. ConclusionsScreened-in reports varied by season and other classifications of time, but temporal dimensions exhibited only a modest influence on the likelihood of substantiation.

WIfI Classification Based Analysis of Risk Factors for Outcomes in Patients with Chronic Limb Threatening Ischaemia after Endovascular Revascularisation Therapy

Evaluating limb status with WIfI classifications and assessing patient risks combined with systemic factors were recommended in patients with chronic limb-threatening ischemic (CLTI). However, there was little application evidence of WIfI in the Chinese population. This study aimed to verify the utilization of the WIfI classification in a China patient population, and further identify local and systemic independent predictors for adverse outcomes of CLTI. A total of 474 patients who underwent endovascular therapy (EVT) for CLTI in a tertiary hospital between July 2017 and September 2020 were included in this retrospective study. The outcomes included 1-year major adverse limb events (MALEs), 1-year all-cause mortality, and 1-year amputation-free survival (AFS). Cox regression was used to analyze the association between risk factors and adverse outcomes. There were 104 (21.9%) all-cause mortalities observed. The MALEs rate was 17.5%, while AFS rate was 71.9%. The multivariate analysis revealed that a BMI < 18.5 kg/㎡ (P = .002), a left ventricular ejection fraction (LVEF) < 50 % (P < .001), and WIfI-Wound Grade (P < .001) were independent risk factors for MALEs, while age ≥ 77 years (P = .031), a BMI < 18.5 kg/㎡ (P < .001), coronary heart disease (P = .040), and WIfI clinical stages (P = .021) were independent risk factors for mortality in CLTI patients. Besides, age ≥ 77 years (P = .003), a BMI < 18.5 kg/㎡ (P < .001), coronary heart disease (P = .012), a LVEF < 50 % (P < .001), WIfI-Wound Grade (P = .004) and WIfI clinical stages (P = .044) were independently associated with a decreased AFS rate. This study confirms the predictive ability of WIfI classification for Chinese CLTI patients who underwent EVT. Wound grade was the most sensitive and important risk factor among the three components of WIfI. In addition, systemic factors should also be considered to ensure a more accurate prognosis prediction and appropriate clinical decision-making in CLTI patients.

Decisional Role of Interim PET in Relapsed/Refractory Classical Hodgkin Lymphoma Treated with Begev Chemotherapy As First Salvage

Achievement of complete response (CR) before autologous stem cell transplantation (ASCT) is one of the main predictive factors of outcome in patients (pts) affected by relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL) eligible to high-dose chemotherapy. The predictive role of interim PET during salvage treatment is well established in pts treated with IGEV or ICE but has not been investigated in pts receiving BEGEV (Bendamustine, Gemcitabine and Vinorelbine) as first salvage treatment. With the aim to investigate the predictive value of PET after 2 cycles of BEGEV (PET2) in terms of CR rate and survival, we retrospectively collected data of consecutive R/R cHL pts eligible to ASCT treated from 2011 to 2021 in 3 Italian centres. PET scans were locally evaluated using Deauville Score (DS), considering a score 1-3 negative and consistent with CR. Early relapse was defined as a relapse occurring ≤12 months from the end of first-line therapy. Survival functions were calculated from the date of initiation of BEGEV chemotherapy. Ninety-four cHL R/R pts receiving BEGEV as first salvage therapy were included. Fifty-one (54.3%) pts were male. First-line therapy consisted in 2 to 6 ABVD chemotherapy cycles accordingly to clinical stage followed by consolidation radiotherapy (RT) in 24 (25.5%) pts. At relapse, median age was 37 years (range: 18-71 years), 51 (54.3%) pts were in stage III-IV, 16 (17%) pts had B symptoms and 34 (36.2%) pts had extranodal involvement (EI). Fifty-one (54.3%) pts were primary refractory, 23 (24.5%) pts had an early and 20 pts (21.3%) a late relapse. PET2 was performed in 86 (91.5%) pts, and resulted negative in 61 (70.9%) and positive in 25 (29.1%) pts (DS 4 in 17 and DS 5 in 8 pts). PET after 4 BEGEV cycles (PET4) was performed in 82 (87.2%) pts and resulted negative in 63 (67%) and positive in 19 (20.2%) pts (DS 4 in 10 and DS 5 in 9 pts). Complete response after 4 BEGEV was achieved in 55/61 (90.2%) PET2 negative pts and 7/25 (28%) PET2 positive pts. Considering pts evaluable for both PET2 and PET4, PET2 positive pts had a statistically lower probability to achieve CR at PET4 when compared to PET2 negative pts (Odds ratio: 0.07, CI 95%: 0.02-0.29; p<0.00001). Autologous SCT was performed in 81 (86.2%) pts, following BEGEV in 56 pts (69.1%) and after further salvage treatments in 25 (30.9%). A post-ASCT consolidation strategy was performed in 24 (29.6%) pts, and consisted in RT in 18 pts and brentuximab-vedotin in 6 pts. Ten pts received an allotransplant: in 3 cases allotransplant was planned in a tandem modality, while in 7 cases was performed after further salvage treatments for post-ASCT relapse or progression. With a median follow-up of 36.4 months (interquartile range: 20.1-50.0), 3-years overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole study population were 91.7%, 61.6% and 53.9%, respectively. No significant differences in OS were detected according to PET2 result. Conversely, both 3-years PFS and EFS were significantly superior in PET2 negative vs PET2 positive pts: 3-years PFS was 61.6% (CI 95%: 52.1-72.9) in PET2 negative and 43.6% (CI 95%: 27.9-68.4) in PET2 positive pts (p=0.0004) (Figure 1), while 3-years EFS was 71% (CI 95%: 59.8-84.3) and 23.3% (CI 95%: 11.3-48.1), (p<0.001). Univariable analysis of PFS was performed using Cox regression model and evaluating adverse risk factors at relapse (primary refractory and early relapse vs late relapse, presence of EN involvement and B-symptoms) and demonstrated a significantly inferior PFS for pts with EI (HR 1.94, CI 95% 1.01-3.74, p=0.47) and primary refractory disease or early relapse (HR 2.02, CI 95%: 1.01-4.04, p=0.047), but not for pts with B symptoms (HR 1.05, CI 95%: 0.43-2.51, p=0.9). Multivariate Cox regression model of PFS evaluating presence of EI at relapse (HR 1.55 , CI 95%: 0.74-3.25, p=0.240), time to relapse (primary refractory and early relapse vs late relapse, HR 0.84 (CI 95%: 0.36-1.96, 0.683) and PET2 result, identified PET2 positivity as the only predictive factor for PFS (HR 3.24, CI 95%: 1.55-6.77, p=0.002). In conclusion, R/R cHL pts with PET2 positive during BEGEV salvage treatment had a lower probability to achieve CR after 2 additional BEGEV cycles and a significantly inferior PFS, and could benefit from early exposure to new therapeutic strategies before ASCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Measurement of skeletal muscle volume is useful for predicting prognosis in patients with liver cirrhosis.

Hepatic venous pressure gradient (HVPG) and the model for end-stage liver disease (MELD) score were previously reported as prognostic factors for outcome in patients with liver cirrhosis (LC), and recently, the presence of sarcopenia was reported to be an indicator of worse prognosis in these patients. This retrospective study aimed to clarify the importance of sarcopenia as a prognostic factor in patients with LC. The MELD-Na score, HVPG, and skeletal muscle index (SMI) were measured in 202 patients between January 2013 and August 2020. We performed linear regression analysis between HVPG and SMI and calculated suitable cutoff values of HVPG for predicting presarcopenia and of HVPG, ΔSMI (i.e. the decrease in SMI per year, for predicting survival). Overall survival rates with the HVPG and ΔSMI cutoff values were compared by Kaplan-Meier estimates and log-rank tests. Prognostic factors for survival were analyzed by Cox regression univariate and multivariate analyses. In total, 71% (143/202) of patients presented with presarcopenia. Linear regression showed a significantly negative correlation between HVPG and SMI. Survival was significantly worse in the group with presarcopenia than in the group without. Survival was worse also in the group with an HVPG value ≥ 15 and ΔSMI ≥ -2.4. Cox regression multivariate analyses showed that MELD-Na score, HVPG, HVPG ≥ 15, ΔSMI, and ΔSMI ≥ -2.4 were independent prognostic factors. Skeletal muscle volume, especially ΔSMI, has a prognostic value equivalent to that of the MELD-Na score and HVPG.

Improving and Promoting Social Determinants of Health at a System Level.

Social determinants of health (SDoH), such as low socioeconomic status, race and ethnicity, poor environmental conditions, food insecurity, and inadequate access to health care services, are known to adversely affect health outcomes. The aim of this project is to address SDoH needs with clinical care to further improve patient outcomes and assist safe discharge. Prime Healthcare Service's model to address SDoH needs focused on supplementing its existing care coordination process with digital innovation while leveraging its highly skilled multidisciplinary team of physicians and mid-level providers, care coordinators, case managers, and social workers and strengthening its relationships with community partners. Prime extended the scope of its services by growing its providers and care navigators' presence in the community to assess needs and foster hospital-community relationships to meet the needs of individual patients. The 2021 Lown Hospital Index, which includes matrices Equity, Value, and Outcomes, has ranked Prime Healthcare Services, as a system, #1 overall in New Jersey and Nevada states. It also ranked Saint Michael's Medical Center number 2 in New Jersey for social responsibility, Centinela Hospital Medical Center number 9 in California for clinical outcomes, and St. Joseph Medical Center number 3 in Missouri for outcomes. The Index also ranked North Vista Hospital as the number 1 most racially inclusive hospital in Nevada. The acute myocardial infarction (AMI) 30-day risk-standardized mortality rate was reduced by an average 1% across the system, while the risk-standardized AMI complication rate was at 0%. Development of an SDoH screening tool, prioritizing high-risk factors, involving a multidisciplinary team, and strengthening the post-acute network have helped address and link the role of SDoH factors in patient outcomes and has resulted in reduced readmission rate, lower mortality and complications rate, and improved cost alignment with the Centers for Medicare & Medicaid Services payment reforms initiative and value-based care.

Obstacles to home-based dietary management for caregivers of children with citrin deficiency: a qualitative study

BackgroundDietary management is the most important and effective treatment for citrin deficiency, as well as a decisive factor in the clinical outcome of patients. However, the dietary management ability of caregivers of children with citrin deficiency is generally poor, especially in East Asia where carbohydrate-based diets are predominant. The aim of this study was to identify the difficulties that caregivers encounter in the process of home-based dietary management, and the reasons responsible for these challenges.ResultsA total of 26 caregivers of children with citrin deficiency were recruited, including 24 mothers, one father, and one grandmother. Grounded theory was employed to identify three themes (covering 12 sub-themes) related to the dilemma of dietary management: dietary management that is difficult to implement; conflicts with traditional concepts; and the notion that children are only a part of family life. The first theme describes the objective difficulties that caregivers encounter in the process of dietary management; the second theme describes the underlying reasons responsible for the non-adherent behavior of caregivers; the third theme further reveals the self-compromise by caregivers in the face of multiple difficulties.ConclusionsThis study reflects the adverse effects of multi-dimensional contradictions on the adherence of caregivers to dietary management. These findings reveal that the dietary management of citrin deficiency is not only a rational process, rather it is deeply embedded in family, social, and dietary traditions.

Biological and psychosocial factors associated with the persistence of pruritus symptoms: protocol for a prospective, exploratory observational study in Germany (individual project of the Interdisciplinary SOMACROSS Research Unit [RU 5211

IntroductionChronic pruritus (CP) is a symptom of dermatologic, neurologic, systemic and psychosomatic diseases. CP has a prevalence of ~20% in the general population and is therefore a significant burden on...

Primary tumor volume and prognosis for patients with p16-positive and p16-negative oropharyngeal squamous cell carcinoma treated with radiation therapy

BackgroundThe prescribed radiation dose to patients with oropharyngeal squamous cell carcinoma (OPSCC) is standardized, even if the prognosis for individual patients may differ. Easy-at-hand pre-treatment risk stratification methods are valuable to individualize therapy. In the current study we assessed the prognostic impact of primary tumor volume for p16-positive and p16-negative tumors and in relationship to other prognostic factors for outcome in patients with OPSCC treated with primary radiation therapy (RT).MethodsFive hundred twenty-three OPSCC patients with p16-status treated with primary RT (68.0 Gy to 73.1 Gy in 7 weeks, or 68.0 Gy in 4.5 weeks), with or without concurrent chemotherapy, within three prospective trials were included in the study. Local failure (LF), progression free survival (PFS) and overall survival (OS) in relationship to the size of the primary gross tumor volume (GTV-T) and other prognostic factors were investigated. Efficiency of intensified RT (RT with total dose 73.1 Gy or given within 4.5 weeks) was analyzed in relationship to tumor volume.ResultsThe volume of GTV-T and p16-status were found to be the strongest prognostic markers for LF, PFS and OS. For p16-positive tumors, an increase in tumor volume had a significantly higher negative prognostic impact compared with p16-negative tumors. Within a T-classification, patients with a smaller tumor, compared with a larger tumor, had a better prognosis. The importance of tumor volume remained after adjusting for nodal status, age, performance status, smoking status, sex, and hemoglobin-level. The adjusted hazard ratio for OS per cm3 increase in tumor volume was 2.3% (95% CI 0–4.9) for p16-positive and 1.3% (95% 0.3–2.2) for p16-negative. Exploratory analyses suggested that intensified RT could mitigate the negative impact of a large tumor volume.ConclusionsOutcome for patients with OPSCC treated with RT is largely determined by tumor volume, even when adjusting for other established prognostic factors. Tumor volume is significantly more influential for patients with p16-positive tumors. Patients with large tumor volumes might benefit by intensified RT to improve survival.

Impact of trial-eligibility as factor for clinical outcome of patients with renal cell carcinoma treated with first-line pazopanib: Subgroup analysis from the prospective, non-interventional study PAZOREAL.

e16511 Background: In a real-world setting, a substantial number of patients (pts) with metastatic renal cell carcinoma (mRCC) do not meet all eligibility criteria for a clinical trial. Thus, data on effectiveness and safety of 1st-line (1L) treatment with pazopanib (PAZO) as well as quality of life (QoL) is underrepresented for those pts and data on treatment sequences implementing PAZO as 1L are sparse. Methods: PAZOREAL is a prospective, multi-center, non-interventional study to evaluate effectiveness, safety and QoL in pts with mRCC treated with 1L PAZO, and nivolumab (NIVO) or everolimus in second and third line. In this subgroup analysis, the clinical outcome of trial-eligible (TE) and trial-ineligible (TIE) pts with mRCC was assessed by means of overall survival (OS), time on drug (ToD), treatment-emergent adverse events (TEAE) and QoL evaluated by EQ-5D-5L. Pts were rated TIE if they met at least one of the following three ‘TIE criteria’: (i) Karnofsky Performance Status &lt; 70%, (ii) hemoglobin below the lower limit of normal, and (iii) non-clear cell carcinoma1. Results: Of 398 pts treated between December 2015 and February 2021, 376 pts received 1L treatment with PAZO. The median age was 69.7 years. 146 pts were categorized TE and 184 pts TIE, for 46 pts assessment was not applicable. Most of all pts were initially treated with PAZO 800 mg (TE: 71.9% vs TIE: 63.0%). Median ToD for PAZO was 7.7 months (95% CI 6.1-9.0) for TE and 6.0 months (95% CI 4.5-8.1) for TIE. A similar fraction of TE and TIE pts were treated with 2L NIVO (43.8% vs 44.0%). Median OS was 53.2 months (95% CI 38.9-NA) for TE and 26.0 months (95% CI 17.3-35.9) for TIE. The 12-month OS rate was 77.9% for TE and 67.1% for TIE. In patient reported outcome (PRO) measures, baseline QoL was estimated higher for TE than TIE, i.e., 63.2% TE vs 49.2% TIE pts had no limitations for mobility and 82.9% TE vs 61.7% TIE pts were independent in self-care. Frequency of related TEAEs grade 3/4 were comparable for TE and TIE (26.7% vs 25.0%), while TE tended to have less related serious TEAEs (13.0% vs 16.3%). Treatment was discontinued due to related TEAEs in 19.2% of TE and 13.0% of TIE pts. Conclusions: PAZOREAL provides real-world data for mRCC pts usually not represented in clinical trials during the study period. As it was to be expected, median OS and PRO were more favorable for TE than for the TIE pts, reflecting the difference in general condition between these groups. But more importantly, these data underline the tolerability of 1L PAZO treatment even for TIE pts, which is supported by comparable ToD for 1L PAZO and the comparable safety profile in both subgroups.1 Marschner, N. et al. Clin Genitourin Cancer 2017; 15(2):e209-215. doi:10.1016/j.clgc.2016.08.022.

Correlation Between Components of Malnutrition Diagnosed by Global Leadership Initiative on Malnutrition Criteria and the Clinical Outcomes in Gastric Cancer Patients: A Propensity Score Matching Analysis.

ObjectiveMalnutrition is recognized as a risk factor for poor outcome in patients with gastric cancer (GC). In 2018, the Global Leadership Initiative on Malnutrition (GLIM) published standardized criteria for the diagnosis of malnutrition. Our aim was to investigate whether any of the components of the GLIM diagnostic criteria were related to worse clinical outcomes in patients with GC.MethodsThis study analyzed patients with GC who underwent radical gastrectomy in our hospital between 2014 and 2019. A preoperative nutritional assessment was performed for each patient. Matching was based on the presence of three GLIM components: high weight loss (WL), low body mass index (BMI), and low skeletal muscle index (SMI).ResultsThe analysis included 1,188 patients, including 241 (20.3%) with high WL, 156 (13.1%) with low BMI, and 355 (29.9%) with low SMI. Before matching, patients who met the GLIM component criteria were mostly associated with older age, low nutritional reserves, and late tumor progression. After matching, the clinical characteristics of the three cohorts were balanced. In the matched queue, the survival prognosis of the high WL group was worse than that of the non-WL group, and the postoperative complication rate was higher in the low SMI group than in the normal SMI group (P <0.05). In addition, the clinical outcomes in the low and normal BMI groups were similar (P >0.05).ConclusionOf the GLIM criteria, high WL and low SMI may be associated with poor clinical outcomes in patients with GC, while a low BMI may not be associated with outcome.

Characteristics Patients with Borderline Ovarian Tumor at Sanglah General Hospital: From Pre- to Post-operative Approach

BACKGROUND: Specific epidemiology data of borderline ovarian tumor (BOT) might be beneficial for the early diagnosis of BOT. The scarcity of BOT epidemiological data in Indonesia urged the writer to study further. AIM: The objectives of the study were to obtain the characteristics of BOT patients in Sanglah General Hospital between 2018 and 2019 according to sociodemographic, hormonal, clinical, and patient outcome factors. METHODOLOGY: This is a descriptive retrospective study. Data were obtained from patient’s medical records at medical records installation Sanglah General Hospital between March 2020 and July 2020. Descriptive data collected from medical records were analyzed using Microsoft Excel 2010 and presented in tables and narrative form. RESULTS: From sociodemographic factors, we found that majority of BOT patients were &gt;40 years old, multiparous women, married, low educated, housewives, and had normal BMI. From hormonal factors, we found that experienced menarche between 11 and 15 years old, most of the patients were already menopause, did not use any contraception. From clinical factors, we found that many were referral cases, with abdominal pain as the main complaint, varied CA 125 and risk of malignancy index levels, unilateral mass, suspected with malignant ovarian cyst when being diagnosed earlier. From patient outcome factors, we found that the majority underwent definitive surgery with no post-operative CA 125 level, no malignant cells on cytology examination, borderline mucinous type in both frozen section and paraffin block examination, and followed up after surgery. CONCLUSIONS: Clinicians could use these characteristics as a reference in diagnosing a patient who fits the profile.

Predictive factors of outcome in patients with Tetralogy of Fallot (TOF) after pulmonary valve replacement: preliminary data of our Centre experience (2010-2020)

Abstract Funding Acknowledgements Type of funding sources: None. Background TOF patients undergo multiple surgical procedures during their life. The improvement in surgical techniques and patient’s clinical management led to longer life expectancy, creating an adult TOF population that experiences specific adverse events, such as atrial/ventricular arrythmias, heart failure and sudden cardiac death. In selected patients, pulmonary valve replacement (PVR) is mandatory to reduce right ventricular (RV) volume; therefore, careful patients’ selection but also correct timing of PVR are crucial. Purpose Current guidelines are based on pre-PVR threshold values of indexed RV end-diastolic volume (RVEDVi) calculated with cardiac magnetic resonance (CMR), to achieve normalization of RV size after valve implantation, but recent studies demonstrated that post-PVR RV dilatation is not so tightly connected with adverse clinical outcomes. Therefore, our aim is to identify new possible predictive factors of post-PVR outcome to provide tailored PVR on the correct cohort of patients, at the correct time. Methods: The inclusion criteria of this retrospective and partially prospective cohort study were i) repaired TOF; ii) available CMR data pre- and post-PVR; iii) PVR performed between 2010 and 2020; iv) clinical and ECG available pre- and post-PVR; v) complete echocardiographic examination pre- and post-PVR. Multivariate analysis was applied. Primary outcomes were considered death, resuscitated death, atrial/ventricular arrhythmias. NYHA class was considered to evaluate patients’ clinical status. CMR Late Gadolinium Enhancement (LGE) score was calculated pre- and post-PVR. Results 22 patients were selected (12 males, median age ± SD 28,25 ± 11,2 years). After PVR, the only primary outcome observed was sustained ventricular tachycardia in 4 patients. Multivariate analysis showed that patients with later PVR, lower Fractional Area Change (FAC) at pre-PVR echocardiogram and higher LGE score post-PVR (LGE &amp;gt; 3) showed higher post-PVR RVEDVi. On the contrary, patients with class I NYHA post-PVR showed lower RVEDVi. Conclusion Our study demonstrates that lower age at PVR and careful patient’s selection, guided by echocardiographic and CMR findings, lead to greater benefit in terms of good volumetric recovery of the RV and better performance status post-PVR (NYHA class I) in TOF patients after PVR.

Mitigation of Blood Load Impact in Patients with Subarachnoid Hemorrhage by Cisternal Lavage

Object: The initial amount of subarachnoid and ventricular blood is an important prognostic factor for outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this comparative study of an unselected aSAH-population, we assess the modifiability of these factors by implementation of blood clearance by cisternal lavage. Methods: All patients with aSAH treated in our department between October 2011 and October 2019 (8 years, n = 458) were included in our study. In the first 4-year period (BEFORE, n = 237), patients were treated according to international guidelines. In the second 4-year period (AFTER, n = 221), cisternal lavage methods were available and applied in 72 high-risk patients (32.5%). The cisternal and ventricular blood load was recorded by the Hijdra score. Multivariable regression models were used to assess the prognostic significance of risk factors, including blood load, in relation to common aSAH characteristics in both study groups. Results: Worse neurological outcomes (mRS > 3) occurred in the BEFORE population with 41.45% versus 30.77% in the AFTER cohort, 6 months after aSAH (HR: 1.59, 95% CI 1.08–2.34, p = 0.01). Admission WFNS grade, comorbidities (Charlson Comorbidity Index), herniation signs, concomitant intracerebral hemorrhage, and the development of delayed cerebral infarction were strongly associated with poor outcome in both study groups. Intraventricular and cisternal blood load and, particularly, a cast fourth ventricle (Cast 4) represented strong prognosticators of poor neurological outcome in the BEFORE cohort. This effect was lost after implementation of cisternal lavage (AFTER cohort). Conclusion: Cisternal and ventricular blood load – in particular: a Cast 4 – represent important prognosticators in patients with aSAH. They are, however, amenable to modification by blood clearing therapies.

Predictive Role of Admission Venous Lactate Level in Patients with Upper Gastrointestinal Bleeding: A Prospective Observational Study.

Upper gastrointestinal bleeding (UGIB) is one of the most common emergencies. Risk stratification is essential in patients with this potentially life-threatening condition. The aim of this prospective study was to evaluate the usefulness of the admission venous lactate level in predicting clinical outcomes in patients with UGIB. All consecutive adult patients hospitalized due to UGIB were included in the study. The clinical data included the demographic characteristics of the observed population, etiology of UGIB, need for surgical intervention and intensive care, bleeding recurrence, and mortality rates. Venous lactate was measured in all patients on admission. Logistic regression analyses were used to calculate the odds ratios (OR) of lactate levels for all outcomes. The receiver operating characteristic (ROC) curve was used to determine the accuracy of lactate levels in measuring clinical outcomes, while Youden index was used to calculate the best cut-off points. A total of 221 patients were included in the study (151M; 70F). There were 24 cases of UGIB recurrence (10.8%), 19 patients (8.6%) required surgery, and 37 individuals (16.7%) required intensive care. Mortality rate was 11.3% (25 cases). The logistic regression analysis showed statistically significant association between admission venous lactate and all clinical outcomes: mortality (OR = 1.39, 95%CI: 1.22–1.58, p < 0.001), recurrence of bleeding (OR = 1.16, 95%CI: 1.06; 1.28, p = 0.002), surgical intervention (OR = 1.17, 95%CI: 1.06–1.3, p = 0.002) and intensive care (OR = 1.33, 95%CI: 1.19–1.5, p < 0.001). The ROC curve analysis showed a high predictive value of lactate levels for all outcomes, especially mortality: cut-off point 4.3 (AUC = 0.82, 95%CI: 0.72–0.92, p < 0.001) and intensive care: cut-off point 4.2 (AUC = 0.76, 95%CI: 0.66–0.85, p < 0.001). Admission venous lactate level may be a useful predictive factor of clinical outcomes in patients with UGIB.