Long-term Benefits For Patients Research Articles

A pre-treatment CT-based weighted radiomic approach combined with clinical characteristics to predict durable clinical benefits of immunotherapy in advanced lung cancer.

To develop a pre-treatment CT-based predictive model to anticipate inoperable lung cancer patients' progression-free survival (PFS) to immunotherapy. This single-center retrospective study developed and cross-validated a radiomic model in 185 patients and tested it in 48 patients. The binary endpoint is the durable clinical benefit (DCB, PFS ≥ 6 months) and non-DCB (NDCB, PFS < 6 months). Radiomic features were extracted from multiple intrapulmonary lesions and weighted by an attention-based multiple-instance learning model. Aggregated features were then selected through L2-regularized ridge regression. Five machine-learning classifiers were conducted to build predictive models using radiomic and clinical features alone and then together. Lastly, the predictive value of the model with the best performance was validated by Kaplan-Meier survival analysis. The predictive models based on the weighted radiomic approach showed superior performance across all classifiers (AUCs: 0.75-0.82) compared with the largest lesion approach (AUCs: 0.70-0.78) and the average sum approach (AUCs: 0.64-0.80). Among them, the logistic regression model yielded the most balanced performance (AUC = 0.87 [95%CI 0.84-0.89], 0.75 [0.68-0.82], 0.80 [0.68-0.92] in the training, validation, and test cohort respectively). The addition of five clinical characteristics significantly enhanced the performance of radiomic-only model (train: AUC 0.91 [0.89-0.93], p = .042; validation: AUC 0.86 [0.80-0.91], p = .011; test: AUC 0.86 [0.76-0.96], p = .026). Kaplan-Meier analysis of the radiomic-based predictive models showed a clear stratification between classifier-predicted DCB versus NDCB for PFS (HR = 2.40-2.95, p < 0.05). The adoption of weighted radiomic features from multiple intrapulmonary lesions has the potential to predict long-term PFS benefits for patients who are candidates for PD-1/PD-L1 immunotherapies. • Weighted radiomic-based model derived from multiple intrapulmonary lesions on pre-treatment CT images has the potential to predict durable clinical benefits of immunotherapy in lung cancer. • Early line immunotherapy is associated with longer progression-free survival in advanced lung cancer.

Effectiveness of percutaneous epidural neuroplasty using a balloon catheter in patients with chronic spinal stenosis accompanying mild spondylolisthesis: a longitudinal cohort study.

Degenerative lumbar spondylolisthesis (DLS) is frequently associated with lumbar spinal stenosis (LSS) and conservative treatments such as epidural steroid injection do not have long-term benefits in LSS patients with DLS. This study evaluated the effectiveness of percutaneous epidural neuroplasty using a balloon catheter in patients with LSS and DLS. Patients' sex, age, body mass index, diabetes, hypertension, stenosis grading, pain duration, location, pain intensity, and medications were retrieved from electronic medical records. At 1, 3, and 6 months following the procedure, data on pain severity, medication usage, and physical functional status were analyzed. A generalized estimating equations model was used at the six-month follow-up. Patients were divided into those with DLS (the spondylolisthesis group) and those without DLS (the no spondylolisthesis group) to evaluate whether the effects of percutaneous epidural neuroplasty using a balloon catheter were different. A total of 826 patients were included (spondylolisthesis: 433 patients, 52.4%; no spondylolisthesis: 393 patients, 47.6%). Age, body mass index, hypertension, pain location, and stenosis grading were statistically different between the two groups. The generalized estimating equations analyses with unadjusted and adjusted estimation revealed a significant improvement in the estimated mean numerical rating scale of pain intensities compared to that at baseline in both groups (P < 0.001). Any adverse events that occurred were minor and temporary. Percutaneous epidural neuroplasty using a balloon catheter may be an alternative treatment option for patients with chronic LSS, regardless of accompanying DLS, who have had failed conservative management.

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

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

Health-Related Quality of Life and Work Satisfaction in Working-Aged Adults Pre- and Post-Cochlear Implant: A Longitudinal Study.

Hearing loss is a growing public health concern associated with decreased health-related quality of life (HRQoL) and a negative impact on work life. Knowledge about the long-term benefits for patients receiving cochlear implants may provide knowledge imperative for policymakers to promote better HRQoL and working life outcomes for individuals with hearing loss. The purpose of this study was to explore how HRQoL, hearing disabilities, and work satisfaction outcomes changed in working-aged adults with severe to profound hearing loss from pre- to post-receiving a cochlear implant (CI) between the baseline, year one, and year two. This longitudinal study used Cochlear's Implant Recipient Observational Study (IROS) registry data to assess HRQoL, hearing disabilities, and work satisfaction in 18-65-year-old CI recipients. Data were collected pre- and post-implantation at baseline, year one, and year two follow-up. One hundred and twenty-seven CI recipients participated in the study. Significant improvements were observed for HRQoL outcomes for hearing, speech, emotion, and health utility post-implant. Overall hearing disability decreased post-CI, and work satisfaction improved. With the increasing prevalence of hearing disabilities, this is pertinent knowledge that supports the use of CIs for hearing rehabilitation which may promote better HRQoL and work satisfaction.

Abstract 10390: Using a Trial Modelling Framework to Emulate a Target Trial Evaluating Revascularisation Strategies in Patients With Heart Failure

Introduction: We developed a novel trial modelling framework which utilises real world data to emulate a target trial and estimate key parameters to support trial planning. We applied this framework using the UK Hospital Episode Statistics (HES), which captures all admissions at NHS hospitals in England, and reported the findings of an emulated target trial evaluating revascularisation strategies in heart failure (HF) patients with coronary artery disease. Methods: Phenotyping algorithms derived from the target trial protocol were applied to HES, to identify HF patients who had coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA). Trial participants are often different from the target trial population due to voluntary basis of participation. The HES-derived cohort was matched on baseline features (age, gender, comorbidities) to an existing trial (STICH) which targeted the same high-risk population, so that the matched cohort mimics a likely trial population. Treatment effects were estimated using instrumental variable analysis (IVA) and meta-learning models to adjust for confounding. Results: A total of 13,519 HF patients undergoing revascularisation during April 2009 and March 2015 met the eligibility criteria. This HF patient cohort was matched with the STICH cohort, resulting in 2046 patients in the study cohort. The 5-year composite outcome of all-cause mortality or cardiovascular hospitalisation was observed in 51.1% of HF patients who had CABG and 70.0% in those who had PTCA. IVA showed that CABG was associated with a lower risk of the composite outcome (risk difference -16.2%, 95%CI: -20.6% to -11.8%). This was consistent with the treatment effects derived from other machine learning models. Our analyses also identified a trend in greater treatment effects being observed in the matched cohort than unmatched cohort. This suggests that a clinical trial may over-estimate treatment effects when compared to the actual treatment benefit observed in clinical practice. Conclusions: The framework provides a structured process to emulate a trial and anticipate findings of the trial. Our analyses showed that CABG is associated with a greater long-term benefit in HF patients requiring revascularisation.

CD123-Targeted Therapy Shows Long-Term Benefit for BPDCN Patients

CD123-Targeted Therapy Shows Long-Term Benefit for BPDCN Patients

Association between left ventricular reverse remodeling and long-term outcomes after alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

There is a paucity of data regarding the effect of left ventricular (LV) reverse remodeling (r-LVR) on diastolic function and outcomes after alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). The aim of this study was to identify the impact of r-LVR on the outcome and the predictors of such changes after ASA. Eighty-seven patients (57.5% men) were enrolled and underwent both echocardiography and cardiovascular magnetic resonance (CMR) imaging at baseline and 27 months after the procedure. The study population was divided into two groups by the degree of r-LVR. Compared to the greater r-LVR group, the lesser r-LVR group had a significantly larger LV mass (LVM) and lower diastolic function parameters at baseline. The greater r-LVR group had significantly greater LVM regression and improvement of diastolic function after ASA. Kaplan‒Meier analysis showed significantly worse composite events in the lesser r-LVR group after ASA (P = 0.016). After adjusting for multiple clinical variables, r-LVR was associated with an improved E/e' (β = 0.390, p < 0.001) and reduced events (hazard ratio: 0.795; 95% confidence interval (CI), 0.644-0.983; p = 0.034). Preablation LVM was associated with a decreased probability of r-LVR (β = -0.228, p = 0.021) and diastolic function improvement (β= -0.245, p = 0.006). r-LVR was associated with long-term outcome benefit in patients with HOCM. Preablation LVM prevented LV from favoring reverse remodeling and thus may be a potential parameter for risk stratification and prognosis after ASA treatment.

Hypergammaglobulinemia before Starting DAA Therapy Is A Strong Predictor of Disease Progression in Cirrhotic Patients Even after HCV Clearance.

The predictive factors of long-term clinical benefits in patients with hepatitis C virus (HCV)—related liver cirrhosis after Direct Antiviral Agents (DAA) treatment are still undefined. The aim of this study was to identify any predictors of liver failure, hepatocellular carcinoma (HCC) and/or death in patients with compensated liver cirrhosis who achieved the sustained virological response (SVR). To this purpose, 324 consecutive cirrhotic patients who started DAA treatment from 1 April 2015 to 31 December 2016 were retrospectively analyzed. All patients were followed up for a median time of 63 months (range 19−77) through clinical/biochemical/instrumental examinations performed at baseline and after stopping the DAA treatment. At the end of the evaluation, 230 (71%) individuals showed stable clinical liver disease over time, 43 (13.3%) developed HCC, and 24 (7.4%) developed hepatic decompensation without HCC. Overall, 49 (15,1%) patients died. Multivariate regression analysis showed that hepatic decompensation was significantly associated with at baseline older age, higher liver stiffness, higher spleen longitudinal size values and hypergammaglobulinemia (p = 0.003, p = 0.005, p = 0.001, p = 0.029, respectively). HCC development was significantly associated with hypergammaglobulinemia (p < 0.001). Death was associated with older age and hypergammaglobulinemia (p < 0.001 and p = 0.007, respectively). Finally, survival analysis confirmed that patients with gamma globulin levels ≥ 1.8 gr/dl had a significantly higher risk of death compared to those with gamma globulin levels < 1.8 gr/dl (p < 0.001). In conclusion, hypergammaglobulinemia before starting DAA therapy represents a strong predictor of hepatic decompensation, HCC and death in cirrhotic patients even after HCV clearance.

Docetaxel, Cisplatin, and 5-FU Triplet Therapy as Conversion Therapy for Locoregionally Advanced Unresectable Esophageal Squamous Cell Carcinoma.

The standard treatment for locoregionally advanced unresectable esophageal squamous cell carcinoma was radical chemoradiotherapy. However, the prognosis was modest. Emerging evidence showed the concept of induction chemotherapy with a goal of conversion surgery. We reviewed the long-term, clinical outcomes and safety data of induction chemotherapy using docetaxel-cisplatin-5FU (DCF) and subsequent definitive treatment, either surgery or radical chemoradiotherapy (CRT), in locally advanced unresectable esophageal cancer in Queen Mary Hospital, Hong Kong. A total of 47 patients (median age 62 years, male: 41 (87.2%)) with locoregionally advanced unresectable esophageal cancer received induction DCF. The response rate was 65.9% (complete/partial response: n = 31). After induction DCF, 24 patients (41.4%) had radical surgery and 7 (14.9%) had definitive CRT. The median overall survival (mOS) was significantly longer in patients received subsequent surgery compared with those with definitive CRT (mOS: 40.2 vs. 9.1 months, hazard ratio 3.33, 95% confidence interval 1.22-9.07, p = 0.02) and no definitive treatment (mOS: 40.2 vs. 6.3 months, hazard ratio 8.51, 95% confidence interval 3.7-19.73, p < 0.001). Patients who received surgery, female, and those with supraclavicular lymph node involvement had a better OS. Twenty-one patients (44.7%) developed grade 3/4 adverse events during induction DCF, and two died after chemotherapy because of trachea-esophageal fistula complicated with sepsis. Eleven patients who had surgery had postoperative complications and none had postoperative mortality. Induction DCF and subsequent conversion surgery offered a chance of cure with long-term survival benefit and manageable toxicities in patients with locoregionally advanced unresectable esophageal cancer.

Use of Advanced Flexible Modeling Approaches for Survival Extrapolation from Early Follow-up Data in two Nivolumab Trials in Advanced NSCLC with Extended Follow-up.

Immuno-oncology (IO) therapies are often associated with delayed responses that are deep and durable, manifesting as long-term survival benefits in patients with metastatic cancer. Complex hazard functions arising from IO treatments may limit the accuracy of extrapolations from standard parametric models (SPMs). We evaluated the ability of flexible parametric models (FPMs) to improve survival extrapolations using data from 2 trials involving patients with non-small-cell lung cancer (NSCLC). Our analyses used consecutive database locks (DBLs) at 2-, 3-, and 5-y minimum follow-up from trials evaluating nivolumab versus docetaxel in patients with pretreated metastatic squamous (CheckMate-017) and nonsquamous (CheckMate-057) NSCLC. For each DBL, SPMs, as well as 3 FPMs-landmark response models (LRMs), mixture cure models (MCMs), and Bayesian multiparameter evidence synthesis (B-MPES)-were estimated on nivolumab overall survival (OS). The performance of each parametric model was assessed by comparing milestone restricted mean survival times (RMSTs) and survival probabilities with results obtained from externally validated SPMs. For the 2- and 3-y DBLs of both trials, all models tended to underestimate 5-y OS. Predictions from nonvalidated SPMs fitted to the 2-y DBLs were highly unreliable, whereas extrapolations from FPMs were much more consistent between models fitted to successive DBLs. For CheckMate-017, in which an apparent survival plateau emerges in the 3-y DBL, MCMs fitted to this DBL estimated 5-y OS most accurately (11.6% v. 12.3% observed), and long-term predictions were similar to those from the 5-y validated SPM (20-y RMST: 30.2 v. 30.5 mo). For CheckMate-057, where there is no clear evidence of a survival plateau in the early DBLs, only B-MPES was able to accurately predict 5-y OS (14.1% v. 14.0% observed [3-y DBL]). We demonstrate that the use of FPMs for modeling OS in NSCLC patients from early follow-up data can yield accurate estimates for RMST observed with longer follow-up and provide similar long-term extrapolations to externally validated SPMs based on later data cuts. B-MPES generated reasonable predictions even when fitted to the 2-y DBLs of the studies, whereas MCMs were more reliant on longer-term data to estimate a plateau and therefore performed better from 3 y. Generally, LRM extrapolations were less reliable than those from alternative FPMs and validated SPMs but remained superior to nonvalidated SPMs. Our work demonstrates the potential benefits of using advanced parametric models that incorporate external data sources, such as B-MPES and MCMs, to allow for accurate evaluation of treatment clinical and cost-effectiveness from trial data with limited follow-up. Flexible advanced parametric modeling methods can provide improved survival extrapolations for immuno-oncology cost-effectiveness in health technology assessments from early clinical trial data that better anticipate extended follow-up.Advantages include leveraging additional observable trial data, the systematic integration of external data, and more detailed modeling of underlying processes.Bayesian multiparameter evidence synthesis performed particularly well, with well-matched external data.Mixture cure models also performed well but may require relatively longer follow-up to identify an emergent plateau, depending on the specific setting.Landmark response models offered marginal benefits in this scenario and may require greater numbers in each response group and/or increased follow-up to support improved extrapolation within each subgroup.

Circulating Epstein-Barr virus DNA associated with hepatic impairment and its diagnostic and prognostic role in patients with gastric cancer.

Epstein–Barr virus (EBV) infection may affect all tissues and organs of the body. Little is known about the impact of this entity on its systematic incorporation in patients with gastric cancer (GC). This study enrolled a total of 113 GC patients with EBV infection (EBVaGC) and 167 GC patients without EBV infection (EBVnGC). It was found that the CRP levels (indicative of inflammatory status) were significantly increased in EBVaGC compared with those in EBVnGC (12.11 mg/L vs. 5.72 mg/L, P = 0.008), but WBC and neutrophils counts were similar in both groups (P > 0.05). Consistent elevations in the levels of liver enzymes, ALP and GGT, with incompatible alterations in ALT or AST were observed in EBVaGC. Slightly prolonged coagulation indices, PT and INR, and decreased albumin consistently suggested impaired synthesis capability of the liver in EBVaGC (all P < 0.05). The level of circulating EBV DNA was positively correlated with the level of GGT, tumor marker CA72-4 and the lymphocyte infiltration in tumor tissues (all P < 0.05). Of note, the EBV associated high-lymphocyte infiltrated tissues presented rich CD8 + T cells. Circulating EBV DNA further showed a predictive role in distinguishing EBVaGC from EBVnGC (AUC 0.79, 95% CI 0.73 to 0.85, P < 0.001), and was associated closely with better overall survival (HR 0.45, 95% CI 0.21 to 0.96, P = 0.039). EBV infection in patients with gastric cancer may be linked to hepatic impairment and immune response. Circulating cell-free EBV DNA is not only a biomarker for the screening of an EBV-related GC subtype but is also an independently prognosis factor for the long-term survival benefit in GC patients.

Efficacy and safety of neoadjuvant imatinib therapy for patients with locally advanced rectal gastrointestinal stromal tumors: A multi-center cohort study.

Background: Several issues on neoadjuvant imatinib therapy remain controversial despite its widespread application for rectal gastrointestinal stromal tumors (GIST). We aimed to describe the clinicopathological characteristics of this specific population, and compare the surgical and oncologic outcomes between patients with or without neoadjuvant imatinib therapy. Patients and methods: A cohort of 58 consecutive locally advanced rectal GIST patients receiving surgical treatment between January 2007 and July 2019 at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital was retrospectively analyzed. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Results: There were 33 (56.9%) patients who received neoadjuvant imatinib therapy. Among them, 20 (60.6%) patients had partial response (PR) as their best response, 11 (33.3%) patients had stable disease (SD), and 2 (6.1%) patients had progressive disease (PD). The median tumor size reduced from 5.2 to 4.0 cm after treatment (p < 0.001), and an attained “maximal response” was primarily achieved (32/33) on the 12th month after treatment. The most common adverse event was anemia. There were 27 adverse events occurred, most of which were grade 1 (19/27). With respect to intraoperative and postoperative surgical outcomes, no significant difference was found between patients with or without neoadjuvant Imatinib therapy except that patients with neoadjuvant treatment had a significant higher rate of preventive ileostomy (p = 0.004). Patients received neoadjuvant treatment had a superior 2-years RFS outcome than those without, though the difference was no significant (91.7% vs. 78.9%, p = 0.203). There were no significant differences in the 2-years OS rates (95.2% vs. 91.3%, p = 0.441). Conclusion: Neoadjuvant imatinib therapy is an effective and safe treatment for locally advanced rectal GISTs. Further studies are warranted to validate the long-term prognostic benefit for patients with rectal GISTs receiving neoadjuvant imatinib therapy.

600. TREATMENT OUTCOME OF CLINICALLY UNRESECTABLE ESOPHAGEAL CANCER AFTER NEO-ADJUVANT CHEMOTHERAPY WITH DOCETAXEL, CISPLATIN AND 5-FLUOROURACIL

Abstract Standard therapy for locally advanced unresectable esophageal cancer is neoadjuvant chemotherapy followed by definitive chemoradiotherapy (CRT). However, the prognosis was modest with the mean survival being around 1 year. Emerging evidence shows the efficacy results of using neo-adjuvant chemotherapy docetaxel-cisplatin-5FU (DCF) for locally advanced esophageal tumor. We reviewed the long-term clinical outcomes and safety data of neo-adjuvant chemotherapy DCF and subsequent definitive treatment in locally advanced clinically unresectable esophageal cancer. All patients with locally advanced clinically unresectable esophageal cancer without any distant metastases and received induction DCF (docetaxel 70 mg/ m2 D1, cisplatin 70 mg/ m2 D1, 5-fluorouracil 750 mg/ m2 on D1-5 Q3 weeks for 3 cycles) with an aim for conversion to definitive surgery or CRT were included. Primary outcomes were overall survival (OS) and conversion rate (from unresectable to resectable tumor after DCF). Secondary outcomes include relapse pattern, safety data of chemotherapy and post-op complications. Total 47 patients (median age 62yo, male: 41 (87.2%)) received neo-adjuvant DCF. 24 patients (41.4%) had subsequent surgery and 7 (14.9%) had definitive CRT. The median OS was significantly longer in the surgical group than CRT group (40.2 vs. 9.1months, HR 3.33, 95%CI 1.22–9.07, p=0.02) and no definitive treatment (40.2 vs. 6.3months, HR 8.51, 95%CI 3.7–19.73, p&amp;lt;0.001). Patients with surgery had a lower risk of local relapse (100% vs. 33%, p&amp;lt;0.001) but comparable risk of distant metastasis (47.8% vs. 58.6%, p=0.538) than those without surgery. The incidence of G3/4 adverse events of DCF was 44.7%. 11 patients had post-op complications. Neo-adjuvant chemotherapy with DCF and subsequent conversion surgery offered a chance of cure with long-term survival benefit and manageable toxicities in patients with locally advanced unresectable esophageal cancer.

Can albumin reduce the mortality of patients with cirrhosis and ascites? A meta-analysis of randomized controlled trials.

Albumin therapy in patients with decompensated liver cirrhosis has always been a controversial issue. This study aimed to investigate the efficacy and safety of albumin in reducing mortality and controlling complications in patients with liver cirrhosis and provide a reference for relevant decision-making. Databases such as PubMed, EMBASE, and Web of Science were searched to collect eligible articles published before January 2022, which were analyzed by Revman 5.3. A total of 10 randomized controlled trials (2040 patients) were included. Based on the meta-analysis results, no significant difference in mortality was shown between the albumin administration group and the control group (HR = 1.01; 95% CI, 0.97-1.05; P = 0.62). Subgroup analysis showed that albumin administration had no significant short-term or long-term survival benefits in patients with decompensated liver cirrhosis and increased the risk of pulmonary edema adverse reactions (RR = 3.14; 95% CI, 1.48-6.65; P = 0.003). Subgroup analysis based on albumin administration time showed that short-term (HR = 0.93; 95% CI, 0.76-1.13; P = 0.47) or long-term (HR = 0.97; 95% CI: 0.87-1.08; P = 0.58) administration of albumin could not significantly reduce the mortality of patients with decompensated liver cirrhosis. In contrast, albumin administration could significantly reduce the recurrence rate of ascites (RR = 0.56; 95% CI, 0.46-0.68; P = 0.000). Short-term(<1 month) or long-term (>1 month) administration of albumin can not significantly reduce the mortality of patients with decompensated liver cirrhosis, and a large amount of albumin infusion will increase the risk of pulmonary edema.

Nutrition Telemonitoring for CKD-HD Patients: A Qualitative Study on Patients, Patients’ Families, Medical Teams, and Hospital Management

BACKGROUND: CKD-HD patients require a nutritional monitoring system to control the amount of protein, fluid, sodium, potassium, and phosphate intake to reduce readmission rates and to improve their life quality. The Nutrition Telemonitoring Application (NTA) has a potential to resolve this problem. AIM: Therefore, this study aims to prepare NTA design materials conditioned to the needs of patients, families, medical teams, and hospital management. METHODS: A qualitative study with semi-structured interviews was conducted on 16 informants consisting of patients, families, medical teams, and hospital management teams. Furthermore, a purposive sampling technique was used to recruit participants, and the thematic analysis of the audio recording was conducted. RESULTS: Three main themes and seven sub-themes were identified. First, all participants in support of NTA will be beneficial. Second, NTA implementation requires family, medical team, hospital management, and BPJS (Health Social Security Agency). Third, all participants demand an easy Indonesian language interface equipped with pictures of food portions, additional alarm features, exercise, food recipes, educational videos, and free of charge. CONCLUSIONS: This study provides important insights considering the issues associated with the sustainability of NTA design and long-term benefits for CKD-HD patients.

TP53 and LRP1B Co-Wild Predicts Improved Survival for Patients with LUSC Receiving Anti-PD-L1 Immunotherapy.

Simple SummaryImmune checkpoint inhibitors (ICIs) changed the standard care of patients with lung squamous cell carcinoma (LUSC). It is an urgent need to precisely predict the population’s response to ICIs. The aim of the study was to explore novel biomarkers for LUSC immunotherapy and the potential mechanism. Five hundred and twenty-five Chinese patients with LUSC who underwent targeted sequencing were involved, and TP53 and LRP1B were the genes most frequently correlated to tumor mutational burden (TMB). Further analysis demonstrated that TP53/LRP1B co-wild was associated with improved survival of immunotherapy. Compared with those with TP53/LRP1B mutant, patients with TP53/LRP1B co-wild had lower TMB and chromosome instability, while stronger cytotoxic immune cell infiltrations, which might be the reason for the better clinical outcomes of immunotherapy. These results indicated that TP53/LRP1B co-wild might be regarded as a potential biomarker for guiding anti-PD-L1 immunotherapy in LUSC.Immunotherapy brought long-term benefits for partial patients with lung squamous cell carcinoma (LUSC). The predictor of anti-PD-L1 therapy was controversial and limited in LUSC. We aimed to explore novel biomarker for LUSC immunotherapy and the potential mechanism. Five hundred and twenty-five Chinese patients (Geneplus cohort) with LUSC underwent targeted sequencing and were involved to explore the genomic profiling. TP53 and LRP1B were the most frequently recurrent genes and correlated to higher tumor mutational burden (TMB). We observed that LUSC patients with TP53 and LRP1B co-wild (co-wild type) were associated with better survival of anti-PD-L1 therapy compared with TP53 mutant or LRP1B mutant (mutant type) in POPAR/OAK cohort. Copy-number variation (CNV) and whole genome doubling (WGD) data from TCGA LUSC cohort were obtained to assess the CNV events. There were fewer CNV alterations and lower chromosome instability in patients with TP53/LRP1B co-wild compared with those with TP53/LRP1B mutant. RNA expression data from the TCGA LUSC cohort were collected to explore the differences in RNA expression and tumor immune microenvironment (TIME) between mutant and co-wild groups. The TP53/LRP1B co-wild type had a significantly increased proportion of multiple tumor-infiltrating lymphocytes (TILs), including activated CD8 T cell, activated dendritic cell (DC), and effector memory CD8 T cell. Immune-related gene sets including checkpoint, chemokine, immunostimulatory, MHC and receptors were enriched in the co-wild type. In conclusion, TP53/LRP1B co-wild LUSC conferred an elevated response rate in anti-PD-L1 therapy and improved survival, which was associated with a chromosome-stable phenotype and an activated immune microenvironment.

A novel carbon-fibre adjustable reusable accessory (CARA) for supine breast positioning to reduce toxicity in breast adjuvant radiotherapy: a study protocol for a multicentre phase III randomized controlled trial

BackgroundA novel device for supine positioning in breast radiotherapy for patients with large or pendulous breasts has been developed and tested in phase II studies. This trial is designed to assess the efficacy of the device to reduce skin toxicity and unwanted normal tissue dose in comparison to the current clinical standard for supine breast support during breast radiotherapy.MethodsPatients at high risk for moist desquamation, having infra-mammary fold or lateral ptosis, will be randomized into two arms. Patients in the control arm will receive breast radiotherapy with supine positioning using current standard of care. Patients in the experimental arm will be positioned supine with the novel device. The primary endpoint is the incidence of moist desquamation in the infra-mammary fold. We hypothesize a 20% reduction (from 50 to 30%) in the rate of moist desquamation in the study arm versus the control arm. For 80% power, two-tailed α = 0.05 and 10% loss to follow up, 110 patients will be assigned to each arm. The proportion of patients experiencing moist desquamation in the two arms will be compared using logistic regression adjusting for brassiere cup size, skin fold size, body mass index, smoking status, and dose fractionation schedule. An unadjusted comparison will also be made using the chi-square test, or Fisher’s exact test, if appropriate. Secondary endpoints include dose-volume statistics for the lung and heart, skin dose and clinical parameters including setup time, reproducibility, and staff experience with setup procedures. Patient-reported pain, skin condition interference with sleep and daily activities, and comfort during treatment are also secondary endpoints.DiscussionBased on results from earlier phase II studies, it is expected that the device-enabled elimination of infra-mammary fold should reduce toxicity and improve quality of life for this patient population. Earlier studies showed reduction in dose to organs at risk including lung and heart, indicating potential for other long-term benefits for patients using the device. This study is limited to acute skin toxicity, patient-reported outcomes, and clinical factors to inform integration of the device into standard breast radiotherapy procedures.Trial registrationClinicaltrials.gov identifier: NCT04257396. Registered February 6 2020.

Abstract 863: LKB1 inhibits NFkB to suppress cancer stem cells in triple negative breast cancer

Abstract Breast cancer is the most common malignancy diagnosed in US women and is the second leading global cause of death for women. Triple Negative Breast Cancer (TNBC) is a more aggressive subtype of breast cancer that is categorized by negative expression of estrogen receptors, progesterone receptors, and amplification of HER2/neu. Because of its receptor phenotype, traditional hormone therapy fails to produce significant short- or long-term benefits for patients. Additionally, chemotherapeutic and surgical interventions often result in relapse and development of a more aggressive disease with higher rates of growth, metastasis, and drug resistance. TNBC also tends to affect women younger than 40 as well as black women, making it a disease of disparities. The Liver Kinase B1 (LKB1/STK11) signaling pathway has been well characterized to have a role in defining cellular responses to energy homeostasis, metabolism, as well as tumor suppressive capabilities. It functions as a master regulator through a set of 14 known kinase targets to maintain its role in cell-type specific regulation. Peutz Jeghers Syndrome, a genetic disorder with a predisposition to developing malignancies, and many other solid tumor cancers are associated with a loss of expression, somatic mutation, or functional deficiencies of LKB1 activity. While studies have been done to understand the role of LKB1 signaling, its role and mechanism in the regulation of TNBC remains unknown. We previously demonstrated LKB1 expression to be associated with increased survival rates for patients diagnosed with TNBC. Therefore, we hypothesize that LKB1 activity in TNBC cell lines will inhibit cancer function. To test this, TNBC cell lines were transfected to overexpress LKB1 with vector transfections generated for controls. Initial molecular results demonstrate a reversal of EMT gene expression by qPCR in cells that overexpressed LKB1. Flow cytometry analysis of LKB1 overexpressing cells show a decrease in the GD2+ cancer stem cells (CSCs). Additionally, functional assays show a reduction growth and proliferation in 3D culture systems. Interestingly, there was no effect on proliferation in standard 2D culture conditions. GD2 was previously identified to be regulated by NFkB signaling. Because LKB1 overexpression resulted in the suppression of CSCs, we hypothesized that LKB1 expression suppresses NFkB signaling. To test this, we ran a western blot panel for NFkB antibodies. Interestingly, LKB1 OE cells had lower levels of IKKα, IKKß, and p65 compared to pcDNA controls. This suggests that LKB1 functions to inhibit NFkB signaling, resulting in the suppression of the CSC phenotype in TNBC. To summarize, LKB1 expression inhibits NFkB signaling, which leads to decreased CSCs. This results in reversal of EMT genes and diminished capabilities to form spheres. Future studies will be dedicated to identifying which of the 14 downstream kinases LKB1 activates to exert its functions. Citation Format: Khoa Nguyen, Madlin Alzoubi, Thomas Cheng, Katherine Hebert, Steven Elliott, Hassan Yousefi, Suresh Alahari, Matthew Burow, Bridgette Collins-Burow. LKB1 inhibits NFkB to suppress cancer stem cells in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 863.

Corporeal rehabilitation to manage acute stress in critically ill patients

BackgroundIntensive care unit (ICU) patients often endure discomfort and distress brought about by their medical environment and the subjective experience of their stay. Distress, pain, and loss of control are important predictors of future neuropsychiatric disorders. Depression, anxiety, and post-traumatic stress are common after discharge. We aimed at mitigating acute stress and discomfort via a novel intervention based on body image rehabilitation and rehabilitation of senses performed following a holistic approach guided by positive communication (corporeal rehabilitation care, CRC).ResultsWe conducted a prospective observational study on 297 consecutively enrolled patients participating in at least one CRC session. Benefits of CRC were assessed on both subjective analogical scales of stress, pain, and well-being criteria, and objective clinical measures of dyspnea, respiratory rate, and systolic arterial pressure, just after CRC and long after (a median of 72 min later) to estimate its remote effect. Results showed that CRC had a positive effect on all overt measures of distress (acute stress, pain, discomfort) just after CRC and remotely. This beneficial effect was also observed on dyspnea and respiratory rate. Results also showed that best CRC responders had higher baseline values of stress and heart rate and lower baseline values of well-being score, indicating that the care targeted the population most at risk of developing psychological sequelae. Interestingly, a positive CRC response was associated with a better survival even after adjustment for physiologic severity, indicating a potential to identify patients prompt to better respond to other therapeutics and/or rehabilitation.ConclusionThis study demonstrated the feasibility of an innovative holistic patient-centered care approach and its short-term positive effects on critical parameters that are considered risk factors for post-intensive care syndrome. Further studies are warranted to study long-term benefits for patients, and overall benefits for relatives as well as ICU staff.

Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature.

Currently, ketamine is used in treating multiple pain, mental health, and substance abuse disorders due to rapid-acting analgesic and antidepressant effects. Its limited short-term durability has motivated research into the potential synergistic actions between ketamine and psychotherapy to sustain benefits. This systematic review on ketamine-assisted psychotherapy (KAP) summarizes existing evidence regarding present-day practices. Through rigorous review, seventeen articles that included 603 participants were identified. From available KAP publications, it is apparent that combined treatments can, in specific circumstances, initiate and prolong clinically significant reductions in pain, anxiety, and depressive symptoms, while encouraging rapport and treatment engagement, and promoting abstinence in patients addicted to other substances. Despite much variance in how KAP is applied (route of ketamine administration, ketamine dosage/frequency, psychotherapy modality, overall treatment length), these findings suggest psychotherapy, provided before, during, and following ketamine sessions, can maximize and prolong benefits. Additional large-scale randomized control trials are warranted to understand better the mutually influential relationships between psychotherapy and ketamine in optimizing responsiveness and sustaining long-term benefits in patients with chronic pain. Such investigations will assist in developing standardized practices and maintenance programs.