Long-term Outcome Factors Research Articles

Long term (15 year) complications & outcomes after liver transplantation for primary sclerosing cholangitis: Impact of donor and recipient factors.

With longer survival of patients with PSC undergoing liver transplantation (LT), the frequency and risk factors associated with vascular and biliary complications in the allograft and the impact on long-term outcomes are poorly understood. To assess frequency and risk factors for long term outcomes in patients post-LT for PSC. All LT recipients for advanced stage PSC for non-cholangiocarcinoma indication from 1984-2012, with follow-up through March 2022 (>10+year followup) were idenitfied. 1-, 5-, and 10-yr cumulative risks of complications were estimated using the Aalen-Johansen method, where death was considered a competing risk. Two hundred ninety-three patients (mean age, 47.3±12y), formed our study cohort. One hundred and thirty-four patients received LT before 1995 and the 159 were transplanted after 1995. Over a median (interquartile range) follow-up of 15.0 (10.3-22.1) years, LT was complicated by hepatic artery thrombosis (N=30), portal vein stenosis/thrombosis (N=48), biliary leak (N=47), biliary strictures (N=87), rPSC (N=107), and graft failure (N=70). The 1-, 5-, 10-, and 15-year cumulative incidence of rPSC was 1.0%, 8.0%, 23.5%, and 34.3% respectively. Type of donor and older donor age were associated with increased risk of biliary strictures. Donor age >60 years was associated with increased risk of rPSC. Long-term patient and graft-survival have not changed significantly for patients transplanted for PSC. Controlling transplant related factors such as donor age, prompt identification of vascular and biliary complications early and long-term rigorous followup is recommended to continue to improve on these outcomes.

Long-term analysis of chronic pain associated with lower extremity injuries

IntroductionThe main objective of this study is to examine chronic pain and limping in relation to lower extremity and pelvic fracture location in addition to fracture combinations if multiple fractures are present on the same leg that have not been previously reported. We hypothesize that fracture pattern and location of lower extremity and pelvis fractures of multiple injured patients influence their long-term pain outcome.Materials and methodsRetrospective cohort study. Patients with treated multiple lower limb and pelvic fractures at a level 1 trauma center and followed up for at least 10 years postinjury were assessed. Lower leg pain subdivided into persistent, load-dependent and intermittent pain, as well as limping were recorded by using self-administered patient questionnaires and standardized physical examinations performed by a trauma surgeon. Descriptive statistics were used to present comparative measurements between groups.ResultsFifty-seven percent of patients (n = 301) showed chronic lower limb pain 10 years postinjury. Ten percent of all patients with chronic pain displayed persistent pain, and here the most common fracture combination was tibial shaft fractures in combination with femoral shaft or proximal tibial fractures (13%). One hundred fifty-one patients reported load-dependent pain, with the most common fracture combinations being fractures of the foot in combination with femoral shaft fractures or distal tibial fractures (11%). One hundred twenty patients reported intermittent pain, with the most common fracture combinations involving the shaft of the tibia with either the femoral shaft or distal tibia (9%). Two hundred fifteen patients showed a persistent limp, and here the most common fractures were fractures of the femoral shaft (19%), tibial shaft (17%), and pelvis (15%).ConclusionsIn multiple injured patients with lower extremity injuries, the combination of fractures and their location are critical factors in long-term outcome. Patients with chronic persistent or load-dependent pain often had underlying femoral shaft fractures in combination with joint fractures.

Long-term recovery after critical illness in older adults.

The population is aging, and recent epidemiologic work reveals that an increasing number of older adults are presenting to the ICU with preexisting geriatric syndromes. In this update, we discuss recent literature pertaining to the long-term recovery of older ICU patients and highlight gaps in current knowledge. A recent longitudinal study demonstrated that the incidence of frailty, disability, and multimorbidity among older ICU patients is rising; these geriatric syndromes have all previously been shown to impact long-term recovery. Recent studies have demonstrated the impact of social factors in long-term outcomes after critical illness; for example, social isolation was recently shown to be associated with disability and mortality among older adults in the year after critical illness. Socioeconomic disadvantage is associated with higher rates of dementia and disability following critical illness impacting recovery, and further studies are necessary to better understand factors influencing this disparity. The COVID-19 pandemic disproportionately impacted older adults, resulting in worse outcomes and increased rates of functional decline and social isolation. In considering how to best facilitate recovery for older ICU survivors, transitional care programs may address the unique needs of older adults and help them adapt to new disability if recovery has not been achieved. Recent work demonstrates increasing trends of geriatric syndromes in the ICU, all of which are known to confer increased vulnerability among critically ill older adults and decrease the likelihood of post-ICU recovery. Risk factors are now known to extend beyond geriatric syndromes and include social risk factors and structural inequity. Strategies to improve post-ICU recovery must be viewed with a lens across the continuum of care, with post-ICU recovery programs targeted to the unique needs of older adults.

Differing clinical features between Japanese siblings with cerebrotendinous xanthomatosis with a novel compound heterozygous CYP27A1 mutation: a case report

BackgroundCerebrotendinous xanthomatosis (CTX) is an autosomal-recessive lipid storage disorder caused by mutations in the CYP27A1 gene encoding the key enzyme in the bile acid synthesis, sterol 27-hydroxylase. Here, we report two Japanese CTX siblings with a novel compound heterozygous CYP27A1 mutation, showing different clinical phenotypes and responses to chenodeoxycholic acid (CDCA) therapy.Case presentationThe proband, a 32-year-old man, who had chronic diarrhea, bilateral cataracts, and xanthomas, demonstrated progressive neurological manifestations including ataxia, and spastic paraplegia during a 5-year follow-up period despite normalization of serum cholestanol after initiation of CDCA treatment. He also exhibited cognitive decline although improvement had been observed at the beginning of treatment. Follow-up brain magnetic resonance imaging (MRI) revealed pronounced progressive atrophy in the cerebellum, in addition to expanding hyperintense lesions in the dentate nuclei, posterior limb of the internal capsule, cerebral peduncles, and inferior olives on T2-weighted images. In contrast, the two-year-younger sister of the proband presented with chronic diarrhea, cataracts, xanthomas, and intellectual disability but no other neurological symptoms at the time of diagnosis. CDCA treatment lead to improvement of cognitive function and there were no characteristic CTX-related MRI features during the follow-up period. The siblings shared a paternally inherited c.1420C > T mutation (p.Arg474Trp) and a maternally inherited novel c.1176_1177delGA mutation, predicting p.(Glu392Asp*20).ConclusionsOur cases suggest that early diagnosis and subsequent initiation of CDCA treatment are crucial before the appearance of characteristic MRI findings and severe neurological manifestations related to CTX. Further studies are required to elucidate mechanisms responsible for the clinical diversity of CTX and prognostic factors for long-term outcomes following initiation of CDCA treatment.

Invited commentary on Sadeghi, et al.: Sentinel lymph node biopsy in pediatric Wilms tumor

In the treatment of cancer, identifying lymph node (LN) metastasizes are critically important [1,2] However, it can be a challenge to identify the “right” node or excise the correct number of nodes to be certain that cancer is or is not present. In adult cancers, the use of a minimum number of nodes and biopsy of a sentinel lymph node have now become standard practice [3]. This is less so for pediatric cancers. Identifying LN positive disease in Wilms tumors is essential as LN positivity has been shown to be the most important predictive factors in long term outcome [1,4–6].

OAB-051: Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone (Dara-KRd), autologous transplantation and MRD response-adapted treatment duration and cessation in newly diagnosed Multiple Myeloma (NDMM)

<h3>Background</h3> Daratumumab, when combined with PI or an IMiD increases depth of response in MM. Minimal/measurable residual disease (MRD) is an important prognostic factor for long term outcome in patients (pts) with newly diagnosed MM (NDMM), but has not been used to modify therapy. We treated NDMM pts with daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd) and employed MRD by next generation sequencing (NGS) to guide the use and duration of Dara-KRd post-autologous transplant (AHCT) and treatment cessation in pts with confirmed MRD negativity. <h3>Methods</h3> We enrolled pts with NDMM, CrCl ≥40 ml/min, adequate organ function, ECOG performance status 0-2 with no age limit. There was a planned enrichment for pts with high-risk cytogenetic abnormalities (HRCA). Treatment cycles consisted of daratumumab 16 mg/kg IV days 1,8,15,22 (typical reduction in frequency with subsequent cycles), carfilzomib 56 mg/m2 IV days 1,8,15, lenalidomide 25 mg days 1-21 and dexamethasone 40 mg oral/IV days 1,8,15,22 repeated every 28 days. Pts received 4 cycles of Dara-KRd induction, AHCT, and received 0, 4 or 8 cycles of Dara-KRd consolidation, according to MRD status. MRD was evaluated by NGS (ClonoSEQ®) in all pts at end of induction, post-AHCT, and during each 4-cycle block of Dara-KRd consolidation. Primary endpoint was achievement of MRD negativity (<10-5 as defined by IMWG) in the intention-to-treat population. Pts received therapy until achievement of two consecutive MRD <10-5 (confirmed MRD-negativity). Confirmed MRD-negative pts entered treatment-free observation and MRD surveillance ("MRD-SURE" phase) with surveillance for MRD resurgence 6 months after treatment cessation and yearly thereafter. Pts completing consolidation without confirmed MRD-negativity received standard lenalidomide maintenance. <h3>Results</h3> Among 123 participants, 46 (37%) had 1 and 24 (20%) had 2+ HRCA [gain 1q, t(4;14), t(14;16), t(14;20) or del(17p)]. Median age was 60 y (36-79), 20% had ECOG 2, 21% had high LDH, and 20% R-ISS3. Disease was trackable by NGS-MRD in 96% of pts. Median follow up is 25.1 mo. Most common severe adverse events were pneumonia (N=8), and venous thromboembolism (N=3). Overall, 80% of pts have achieved MRD negativity (78%, 82% and 79% of pts with 0, 1 and 2+ HRCA respectively) and 65% MRD < 10-6 (62%, 73% and 58% of pts with 0, 1 and 2+ HRCA respectively). MRD negativity was reached in 38% of patients post induction, 65% post AHCT and 80% post MRD-directed Dara-KRd consolidation. Response ≥CR was obtained in 86% of pts. Overall 84 pts (71%) have reached confirmed MRD negativity and entered MRD-SURE. <h3>Conclusion</h3> Monoclonal antibody-based quadruplet therapy, AHCT and MRD response-adapted consolidation therapy leads to high rate of MRD negativity in NDMM. For most patients with NDMM, MRD-directed adaptive treatment offers the prospect of confirmed deep responses and investigation of MRD surveillance as an alternative to indefinite maintenance.

Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients.

BackgroundSurgical resection is often the preferred treatment for non-small cell lung cancer (NSCLC) patients. Predictive biomarkers after surgery can help monitoring and treating patients promptly, so as to improve the clinical outcome. In this study, we evaluated one potential candidate biomarker, the folate receptor-positive circulating tumor cell (FR+CTC), by investigating its prognostic and predictive significance in NSCLC patients who underwent surgery.MethodsIn this prospective, observational study, we enrolled NSCLC patients who were eligible to receive surgery. Prior to operation, peripheral blood was collected from each patient for an FR+CTC analysis. FR+CTCs were isolated by negative enrichment using immunomagnetic beads to deplete leukocytes and then quantitatively detected by a ligand-targeted polymerase chain reaction (PCR) method. These patients were then given standard care and were actively followed up for seven years. At the end of the follow-up period, the association between the FR+CTC level and the prognosis in these patients was evaluated.ResultsOverall, preoperative FR+CTC level was not significantly different among NSCLC patients with adenocarcinoma or non-adenocarcinoma subtypes (P = 0.24). However, between patients with low- and high-risk pathological adenocarcinoma subtypes, the preoperative FR+CTC level was significantly different (P = 0.028). Further, patients with lower preoperative FR+CTC level had longer relapse-free survival (RFS) and overall survival (OS) than those with higher preoperative FR+CTC level (RFS: not reached vs. 33.3 months, P = 0.018; OS: not reached vs. 72.0 months, P = 0.13). In a multivariate COX regression analysis, FR+CTC level (HR = 4.10; 95% CI, 1.23–13.64; P=0.022) and pathological stage (HR = 3.16; 95% CI, 1.79–10.14; P = 0.0011) were independent prognostic factors of RFS. Moreover, FR+CTC level together with adenocarcinoma subtypes provided additional information on risk for disease recurrence compared with FR+CTC or adenocarcinoma subtype alone.ConclusionOur study demonstrated that the preoperative FR+CTC level was a potential predictor for the prognosis of NSCLC patients underwent surgery. Further, when preoperative FR+CTC level is considered together with primary tumor proliferation characteristics, its prognostic value supplements that of these conventional pathological features.

Liver resections for colorectal liver metastases in elderly patients

The aim of this study was to evaluate the short- and long-term results and risk factors of liver surgery in patients over the age of 70 following liver resection for colorectal liver metastases. A total of 650 patients with an average age of 63.8 ± 9.3 years were evaluated. We compared groups of patients younger and older than 70 years of age. Time of hospitalisation, 30-day postoperative morbidity and mortality, overall and recurrence-free survival, the number and largest diameter of metastases, small and large liver resections, and the interval between primary colorectal and liver surgery were evaluated according to the results of liver resections. Length of hospitalisation, 30-day postoperative morbidity and mortality, and long-term results did not differ between groups of patients. Pulmonary embolism and confusion had a higher incidence in patients ≥70 years old (p < 0.02 and 0.05, respectively). Diameter of the largest metastasis ≥50 mm was a negative prognostic factor for long-term results in patients ≥70 years old (p < 0.04, HR 1.7, 95% CI 1.0–2.9 and p < 0.03, HR 1.5, 95% CI 1.0–2.3, respectively). Large liver resections had worse long-term results in patients ≥70 years old (p < 0.01, HR 2.1, 95% CI 1.2–3.8 and p < 0.05, HR 1.5, 95% CI 0.9–2.3, respectively). Our results confirm the safety of liver resections for colorectal liver metastases in elderly patients. Parenchymal sparing surgery should be the method of choice. Very early and intensive postoperative mobilisation and respiratory and mental rehabilitation is essential.

CML-366: Baseline Cytogenetic Response Level Impact on Survival of Chronic Phase Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors as Third-Line Therapy: Real-World Data in Five Russian Centers

Context Tyrosine kinase inhibitors in third-line therapy (TKI-3L) in chronic-phase chronic myelogenous leukemia (CP CML) is effective in a portion of patients. Meanwhile, it is unclear which patients may benefit from TKI-3L. Objective To identify the factors affecting the outcome of TKI-3L therapy in CP CML. Design A retrospective study was conducted in five centers of St. Petersburg and Leningrad Region in 2019. All CP CML patients who ever obtained TKI-3L in these centers were included, except patients (pts) with complete cytogenetic response (CCyR). Results Seventy-three pts (male=26) with baseline median age 51 (25–88) were included in the study. There were 51 (70%) pts without any CyR, including 27 (37%) cases without complete hematologic response in baseline. For other patients, the best baseline cytogenetic response was minimal or minor (mmCyR) in 12 (16%) and partial (PCyR) in 10 (14%). BCR-ABL mutations were detected in 30/73 (42%) cases at any time before TKI-3L. Reasons for switching to TKI-3L were resistance in 56 (77%) or intolerance in 17 (23%). Dasatinib, Nilotinib, Bosutinib, or Ponatinib were used as TKI-3L in 43 (59%), 18 (25%), 9 (12%), and 3 (4%) pts, respectively. The median time of TKI-3L treatment duration was 15 (1–120) months. CCyR was achieved in 8/51 (16%) and 14/22 (64%) pts without CyR and with mmCyR/PCyR, respectively(p=0.001). CCyR subsequently had been lost 5/8 (62.5%) and 5/14 (29%) pts initially without or with any CyR (p=0.01). MMR was achieved in 3/51 (6%) and 6/22 (27%) pts without or with any CyR (p>0.05). Estimated overall 1-year, 3-year, and 5-year OS were 95%, 81%, and 65%, respectively. The median follow-up was 26 (3–136) months. There were 14 (19%) death: 11 due to CML progression and 3 after allo-SCT. All deaths occurred in pts without any CyR at baseline. Transformation to accelerated phase and blast crisis was occurred in 13 (18%) pts only in pts group without any CyR initially. The median time to progression was 15 (6–102) months. The only relevant baseline factor for CCyR, OS, and PFS probability in multivariant analysis was the presence of any CyR at baseline (p Conclusion Initial presence of any CyR was a favorable factor for long-term results of TKI third-line treatment in CP CML. TKI-3L should be considered as an appropriate tool in CML treatment for this group.

Feasibility and safety of surgical microwave ablation for hepatocellular carcinoma in elderly patients: a single center analysis in Japan

The feasibility and safety of microwave ablation in elderly hepatocellular carcinoma (HCC) patients remains unknown. The aim of this study was to evaluate the feasibility and safety of surgical microwave ablation for HCC in patients older than 80 years of age. This retrospective study enrolled consecutive 114 patients older than 80 years of age who underwent surgical microwave ablation for HCC between July 1994 and December 2017. We analyzed perioperative outcomes and long-term outcomes to clarify the prognostic factors. The 1-, 3-, 5-year overall survival and recurrence-free survival rates were 97.3%, 76.0%, 49.2% and 84.2%, 44.7%, and 32.5%, respectively. The overall major morbidity rates (Clavien–Dindo grade IIIA or above) were 2.6%. There were no cases of mortality. Multivariate analysis showed that hepatitis C virus antibody (HCV-Ab) positivity and the presence of multiple tumors were independent prognostic factors for long-term outcomes. The overall survival rate of patients with HCV-Ab negative and single tumor was better than that of other patients (p = 0.026). Surgical microwave ablation was feasible and safe for elderly patients with HCC. Elderly patients with HCV-Ab negative and single tumor would be expected to have better long-term outcomes after surgical microwave ablation.

Different efficacy of osimertinib in pre-TKI treated NSCLC patients with brain metastases harboring EGFR exon 19del and L858R mutant.

e21667 Background: Previous studies suggested that the efficacy of osimertinib was better in patients with epidermal growth factor receptor ( EGFR) exon 19 deletion (ex19del) than exon 21 Leu858Arg (L858R). However, the differential clinical outcomes of osimertinib in previous tyrosine kinase inhibitors (TKIs) treated non-small-cell lung cancer (NSCLC) patients with brain metastases (BrMs) according to the two different common EGFR genotypes remains undetermined. Methods: We retrospectively collected EGFR mutant (ex19del and L858R) NSCLC patients with BrMs and received osimertinib treatment between Jan 2016 and Feb 2019 in our hospital. Other eligible standards including Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, osimertinib 80mg monotherapy and neurologic symptoms existing was permitted to enroll in our study. Results: 78 patients with EGFR mutant NSCLC and BrMs were included in the study. EGFR mutation types were ex19del in 55% of patients (43/78) and L858R in 45% of patients (35/78). All of patients received at least one prior EGFR-TKI therapy, among which 46% (36/78) had gefitinib, 49% (38/78) had erlotinib, 19% (15/78) had icotinib. T790M status at osimertinib initiation was positive in 81% of patients (63/78), negative in 4% (3/78), unknown in 15% (12/78). The systemic objective response rate (ORR) was 46%. There was no apparent difference in systemic ORR (49% vs 43%, P = 0.598) between ex19del group and L858R group. The median progression free survival (PFS) and overall survival (OS) were 7.0 (range 4.7-9.3) and 18.8 (range 14.0-23.5) months for all patients. The median PFS in the ex19del and L858R subgroups was 9.1 (range 6.0-12.1) months and 5.3 (range 3.4-7.2) months, respectively ( P = 0.031). The median OS in the ex19del and L858R subgroups was 26.0 (range 13.7-38.3) months and 13.9 (range 7.7-20.2) months, respectively ( P = 0.033). Multivariate analysis identified L858R and ECOG PS 2 as poor independent predictors to the PFS and OS. Conclusions: The efficacy of osimertinib was associated with EGFR genotypes in pre-TKI treated NSCLC patients with BrMs, and L858R maybe an independent bad factor for long-term outcomes of osimertinib.

Role for Vascular Factors in Long-Term Outcomes After Transcatheter Aortic Valve Implantation

Despite major technological advances, 1-year morbi-mortality after transcatheter aortic valve implantation (TAVI) is still high. Further outcome improvements may be obtained provided proper identification of prognostic factors. A change of prognostic value over time should be the hallmark of an outcome-implicated factor. In 1,425 patients treated by TAVI, the examined prognostic factors were: demographic factors and co-morbidities (age, male gender, glomerular filtration rate, and chronic obstructive pulmonary disease), cardiac function (left ventricular ejection fraction, pulmonary pressure, aortic gradient, dyspnea, and mitral regurgitation), and vascular factors (coronary artery disease, peripheral vascular disease (PVD), previous stroke, and thoracic aortic calcium-TAC-as assessed by CT scan). Cox models were used to analyze cardiovascular and all-cause mortalities over 3 years of follow-up. The time-dependent effects of the factors were analyzed using the distribution of Schoenfeld residuals. During the study period, 375 (26.3%) deaths occurred of whom 248 (17.4%) from cardiovascular causes. Only 2 factors associated with cardiovascular or all-cause mortality showed significant changes over time: dyspnea and PVD. The effect of dyspnea on cardiovascular mortality decreased over time (first- and third-year hazard ratios [95% confidence intervals]: 1.47 [1.10; 1.96] and 0.94 [0.55; 1.63], respectively), whereas the effect of PVD increased (first- and third-year hazard ratios: 0.87 [0.56; 1.35] and 2.58 [1.25; 5.33], respectively). TAC had a stable effect. In conclusion, the detrimental effects of vascular factors remained stable (TAC) or increased (PVD) over time. These factors should be targeted by specific measures to improve post-TAVI outcomes.

Early environment and long-term outcomes of preterm infants.

Prematurity is associated with an increased risk of long-term health and neurodevelopmental problems. Key perinatal and neonatal factors that affect these outcomes have long been studied. However, more recently, there has been an appreciation of the importance of environmental factors in long-term outcomes of preterm babies, particularly in light of the rapid maturation of the brain during these babies' early days of life. Breastmilk and breastfeeding is the gold standard for infant feeding, including preterm babies. The benefits are well established in regard to protection from serious complications like necrotising enterocolitis. Although theoretically plausible, the benefits for neurodevelopment are less clear. Noise, pain and the environment of the neonatal intensive care can also affect infant neurodevelopment. It is established that noise and pain have deleterious effects. However, the benefits of single-room vs open-bay neonatal units remain under debate. Developmental care practices, of which there are many, are increasingly embraced worldwide. There are benefits both for the parents and the baby, however, the evidence is difficult to pool due to the heterogeneity of studies and study populations. Finally, it is important to remember the importance of the role of parents in shaping long-term neurodevelopment of the high-risk preterm newborn. Increasingly, positive parenting and parents' mental health are shown to have long lasting advantages for preterm infants. A deeper understanding of early environmental factors is key to developing future interventions to optimise outcomes of preterm newborns.

P5314Albumin is a prognostic marker of long-term outcomes in patients with triple-vessel coronary artery Disease: a large data from China

Abstract Background Hypoalbuminemia was reported to be associated with poor prognosis in severe diseases. Triple-vessel coronary artery disease (TVD) has high risk of death. We aimed to evaluate the predictive value of hypoalbuminemia in TVD patients. Methods A total of 8,943 consecutive TVD patients were enrolled from April 2004 to February 2011. The primary endpoint was all-cause death and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction or stroke). Patients were divided into two groups according to normal serum albumin level (&lt;4.0 g/dL and ≥4.0 g/dL). Results During the median of follow-up 7.5 years, 1365 deaths and 2354 MACCE occurred. Multivariate Cox regression indicated that hypoalbuminaemia (&lt;4.0 g/dL) was an independent predictor of all-cause death (HR 1.30, 95% CI 1.14–1.50, P&lt;0.001) and MACCE (HR 1.19, 95% CI 1.07–1.32, P&lt;0.001). Adjustment of the all-cause death risk estimated by albumin improved the predictive value of SYNTAX score (AUC from 0.585 to 0.602, P=0.002; IDI=0.005, P&lt;0.001; NRI=0.205, P&lt;0.001). For SYNTAX II score, improvement was shown for NRI and IDI but not for AUC (SYNTAX II for PCI: IDI=0.003, P&lt;0.001; NRI=0.205, P&lt;0.001; AUC from 0.711 to 0.713, P=0.257; SYNTAX II for CABG: IDI=0.002, P&lt;0.001; NRI=0.205, P&lt;0.001; AUC from 0.696 to 0.698, P=0.120). Predictive value for all-cause death using the AUC, NRI and IDI AUC (95% CI) P value NRI (95% CI) P value IDI (95% CI) P value SYNTAX 0.585 (0.568–0.602) Ref. Ref. – Ref. – SYNTAX + albumin 0.602 (0.586–0.619) 0.002 0.205 (0.145–0.264) &lt;0.001 0.005 (0.004–0.007) &lt;0.001 SYNTAX II (for PCI) 0.711 (0.696–0.726) Ref. Ref. – Ref. – SYNTAX II (for PCI) + albumin 0.713 (0.698–0.728) 0.257 0.205 (0.145–0.264) &lt;0.001 0.003 (0.001–0.004) &lt;0.001 SYNTAX II (for CABG) 0.696 (0.680–0.711) Ref. Ref. – Ref. – SYNTAX II (for CABG) + albumin 0.698 (0.683–0.714) 0.120 0.205 (0.145–0.264) &lt;0.001 0.002 (0.001–0.004) &lt;0.001 Multi-factor adjusted KM analysis in TVD Conclusions For TVD patients, hypoalbuminaemia was a strong independent prognostic factor for long-term outcomes of death and MACCE. Albumin improved the prediction of death with the SYNTAX score and the SYNTAX II score. Acknowledgement/Funding CAMS Innovation Fund for Medical Sciences (2016-I2M-1-002), Beijing Natural Science Foundation (7181008)

Predictive Factors of Long Term Outcome in MMN

Predictive Factors of Long Term Outcome in MMN

Abstract 4050: Molecular characterization of residual triple-negative breast cancers after neoadjuvant chemotherapy identifies immune composition and features associated with clinical outcome

Abstract Although neoadjuvant chemotherapy (NAC) induces complete response in 30-40% of triple-negative breast cancers (TNBC), patients with residual disease at surgery have poor prognosis and limited treatment options until recurrence. Tumor-infiltrating lymphocytes (TILs) in the residual disease are a positive prognostic factor, but the composition of TILs has not been explored in granularity, and how specific immune composition of the tumor guides outcome is unclear, resulting in a lack of understanding of how to employ immunotherapies in the adjuvant setting. We assessed multiple immunologic biomarkers in a series of 100 residual TNBCs after NAC. Immune markers were assessed by multiple methods, including H&amp;E TILs analysis, standard immunohistochemistry (IHC; HLA-A, CD4, CD8, LAG-3) and multiplexed immunofluorescence (mIF; HLA-DR, GZMB, CD4, CD8, PD-L1, pan-CK). TILs and IHC were scored by clinical research pathologists and IF was scored by AQUA® analysis. Where multiple markers were multiplexed together, subset analyses was performed. Association among parameters were assessed (n=83) including clinical outcome after surgery (n=79). As previously demonstrated, TILs in residual tumors after NAC predicted both RFS and OS. H&amp;E-scored TILs were correlated to both CD4 and CD8 as scored by IHC or IF (Pearson’s r range 0.41-0.55; all p&amp;lt;0.001). CD4 and CD8 measured by IHC and IF were highly correlated (r=0.68 and 0.71, respectively; p&amp;lt;0.0001). CD4 and CD8 were also highly correlated to one another (r=0.67; p&amp;lt;0.0001). Likewise, infiltration by CD4 or CD8 were each associated with improved recurrence-free (RFS; coxPH p=0.004 and 0.007, respectively) and overall survival (OS; p=0.003 and p=0.005, respectively). Tumor and stromal PD-L1 (E1L3N) staining was associated with marginally poorer RFS (p=0.06) but not OS (p=0.94). Colocalizing GZMB and CD8 cells by mIF yielded a paradoxical finding that cytotoxic CD8 cells were associated with significantly worse RFS and OS (p=0.004 and 0.0004, respectively). In a multivariate model, total PD-L1, total CD4, and GZMB+CD8+ T cell infiltration each remained significant, suggesting independence, and provided a strongly predictive signature for RFS (p=4.6e-06). In the same analysis to predict OS, only GZMB+CD8+ T cells remained significant (p=0.0002). High GZMB+ CD8+ T cells were not associated with PD-L1 expression, but were associated with low LAG-3 expression (p=0.0009). Although the results of this study remain to be validated in larger cohorts, the paradoxical finding that GZMB+ CD8+ T cells are a negative prognostic factor for long term outcome in NAC-treated TNBC is an intriguing result. We hypothesize it may be these patients whose T cells are poised for cytotoxic activity but remain restricted through high PD-1 expression, and thus may benefit from adjuvant immunotherapy. Citation Format: Caroline Nebhan, Paula I. Gonzalez-Ericsson, Roberto Salgado, Jennifer Bordeaux, Ju Young Kim, Christine Vaupel, Henry Gomez, Justin Micah Balko. Molecular characterization of residual triple-negative breast cancers after neoadjuvant chemotherapy identifies immune composition and features associated with clinical outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4050.

Predicting visual outcomes in patients treated with aflibercept for neovascular age-related macular degeneration: Data from a real-world clinical setting.

There is a significant variation in the way neovascular age-related macular degeneration patients respond to anti-vascular endothelial growth factor treatment. Both the financial and time cost of treatment are significant. As such, being able to predict patient response to treatment is valuable. 72 eyes treated with intravitreal aflibercept were retrospectively included in analysis. For each subject, visual acuity (letters) and central retinal thickness (µm) at baseline, second, third and fourth visits, as well as 12-month visits, were collated; a plot of visual acuity versus time was generated and a slope of the first three (slope3) and first four (slope4) visits was calculated. Differences in visual acuity at each visit compared to baseline were determined, as well as percentage differences in central retinal thickness at each visit compared to baseline. Lesion sub-type and the presence of fluid and haemorrhage were also recorded. The average change in visual acuity over 12 months was +3.2 ± 13.4 letters with 91.2% of patients losing <15 letters. Slope4 was the only significant predictive factor for 'visual acuity change over 12 months' (p < 0.001). Change in central retinal thickness, lesion sub-type, haemorrhage at baseline and the location of fluid at baseline were not useful predictive factors in long-term outcome. Aflibercept is an effective treatment option for neovascular age-related macular degeneration; however, the long-term response should not be predicted until at least three loading dose injections have been given. Visual acuity measures at each visit should be examined, as it is the trend in visual acuity across the first four visits (slope4) rather than the difference in visual acuity between two visits that is the predictive factor.

Prognostic factors for long-term outcomes in acute decompensated heart failure patients under tolvaptan treatment.

Inconsistent results have been reported concerning the effect of tolvaptan treatment on long-term prognostic outcomes in patients with acute decompensated heart failure (ADHF) and data are limited on prognostic factors affecting this patient population. We investigated prognostic factors influencing long-term clinical outcomes in patients with ADHF treated with tolvaptan in a real-world setting. A total of 263 consecutive patients hospitalized for ADHF and treated with tolvaptan were retrospectively enrolled. The patients were stratified into those who developed the combined event of cardiac death or rehospitalization for worsening heart failure within 1year (n = 108) and those who were free of this combined event within 1year (n = 155). Adjusted multivariate Cox proportional hazards model revealed that change in serum sodium level between pre-treatment and 24h after tolvaptan administration [hazard ratio (HR) 0.913, 95% confidence interval (CI) 0.841-0.989, p = 0.025] and the time taken for tolvaptan initiation from admission (HR 1.043, 95% CI 1.009-1.074, p = 0.015) were independent predictors of combined event occurrence within 1year. Moreover, change in serum sodium level >1mEq/L between pre-treatment and 24h after administration and initiation of tolvaptan <5days after admission correlated significantly with the incidence of the combined event (log-rank test p = 0.003 and p = 0.002, respectively). In conclusion, increased serum sodium level early after administration and early initiation of tolvaptan are possibly useful for assessing the long-term prognosis after tolvaptan treatment in patients with ADHF.

PS02.212: RECURRENCE PATTERN AND RISK FACTOR AFTER ESOPHAGECTOMY FOR ESOPHAGEAL SQUAMOUS CARCINOMA

Abstract Background Surgical procedure of esophageal cancer is invasiveness and perioperative condition for the patient play an important role for outcome. The aim of this study is investigate the impact of operative complication on the recurrence. Methods Between January 2010 and December 2017, total 159 patients, who had been diagnosed esophageal squamous carcinoma and undergone curative radical esophagectomy were enrolled. Results Recurrence was observed for 39 cases (24.5%), median value for recurrence is 493 days after operation. Pathological stage I/II/III/IV were 3/14/17/5 cases, respectively. Preoperative additional therapy was received 16 cases, including 13 cases for neoadjuvant chemotherapy and 3 cases for definitive chemoradiotherapy. The sites of recurrence were observed lymph node in 20 cases, distant metastasis in 10 cases, and three cases of local recurrence. Fifteen patients in recurrent cases are still survivals. Compared with no-recurrence group, there was no significantly difference in operative blood loss, blood transfusion and operative time. Preoperative nutritional condition, such as serum albumin level and number of lymphocyte were not difference in both groups. In addition, sarcopenia and obesity were not associated with recurrence. Concerning as inflammatory complications, anastomotic leakage was not influenced on recurrence, but pneumonia was affected to recurrence. Moreover, three year recurrent free survival was significantly lower in the case of pneumonia as postoperative complication. Conclusion The incidence of recurrence for esophageal squamous carcinoma is high rate, even if early stage of cancer. The site of recurrence is highly revealed as lymph node metastasis. In this study, pneumonia as postoperative complication is strongly contributed to risk factor for long term outcome. Secure postoperative respiratory management is required for improvement of long term prognosis. Disclosure All authors have declared no conflicts of interest.

Long-term outcomes in osteosarcoma patients in the Groote Schuur Hospital patient population: A retrospective review

&lt;strong&gt;Background:&lt;/strong&gt; Predictive factors for long-term outcomes in osteosarcoma patients are still controversial. There is no literature available regarding these factors in a patient population in a developing country.&lt;br /&gt;&lt;strong&gt;Aim and setting:&lt;/strong&gt; To determine the outcome of treatment of osteosarcoma patients treated at Groote Schuur Hospital from 1990 to 2012 in terms of locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) and to determine the value of suggested predictive factors in this population.&lt;br /&gt;&lt;strong&gt;Patients and methods:&lt;/strong&gt; Retrospective review of all patients diagnosed with and treated for osteosarcoma at Groote Schuur Hospital between 1990 and 2012, considering OS, DFS and LRC. This review assesses the significance of suggested predictive factors from other studies, namely, HIV status, age at diagnosis, site of primary disease, type of chemotherapy used, response to chemotherapy and type of surgery in terms of OS, DFS and LRC.&lt;br /&gt;&lt;strong&gt;Results:&lt;/strong&gt; Forty-three patients with histologically confirmed osteosarcoma were treated at Groote Schuur Hospital between 1990 and 2012. Median 5 year OS was 57.8%. On univariate analysis, the site of disease was the only statistically significant predictive factor for prognosis.&lt;br /&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; On univariate analysis, patients with axial disease have a worse predicted prognosis than those with primary disease in their extremities. The clinical behaviour and long-term outcome after treatment of these patients with osteosarcoma are similar to that seen internationally.