Similar Survival Curves Research Articles

Presentation and patterns of reinterventions after revascularization in patients with premature peripheral arterial disease

ObjectivePremature peripheral arterial disease (PAD) (age ≤50 years) has been shown to negatively impact the outcomes of lower extremity revascularization (LER). Patients with premature PAD have an increased risk of major amputation compared with older patients. The primary goal of this study is to compare the frequency of reinterventions after LER in patients with premature PAD to their older counterparts with common age of presentation (ie, 60-80 years). MethodsA retrospective review of consecutive patients undergoing LER for PAD in a single center was performed. Clinical, procedural, and socioeconomic characteristics were compared between patients with premature PAD and the older group. Perioperative and long-term outcomes were captured and compared including mortality, major amputation, reintervention rate and frequency, as well as major adverse limb events. ResultsThere were 1274 patients who underwent LER (4.3% premature, 61.8% age 60-80). Patients with premature PAD were more likely to be females of racial minorities. Notably, the mean Distressed Communities Index score was significantly higher in the premature PAD group compared with the older patients. Patients with premature PAD were significantly more likely to have end-stage renal disease but less likely to have hypertension, hyperlipidemia, and coronary artery disease compared with older patients. There was no significant difference in perioperative complications. After a mean follow-up of 5 years, patients with premature PAD were significantly more likely to undergo more frequent reinterventions compared with older patients. Kaplan-Meier curves showed similar overall survival and major adverse limb event-free survival between the two groups. ConclusionsPatients with premature PAD are likely to undergo more frequent reinterventions after initial LER and have similar 5-year survival curves compared with patients at least 20 years older. Demographic and socioeconomic differences impacting patients with premature PAD, even in this relatively underpowered institutional experience, are striking and warrant further investigation.

Establishment of artificial intelligence model for precise histological subtyping of lung adenocarcinoma and its application to quantitative and spatial analysis.

The histological subtype of lung adenocarcinoma is a major prognostic factor. We developed a new artificial intelligence model to classify lung adenocarcinoma images into seven histological subtypes and adopted the model for whole-slide images to investigate the relationship between the distribution of histological subtypes and clinicopathological factors. Using histological subtype images, which are typical for pathologists, we trained and validated an artificial intelligence model. Then, the model was applied to whole-slide images of resected lung adenocarcinoma specimens from 147 cases. The model achieved an accuracy of 99.7% in training sets and 90.4% in validation sets consisting of typical tiles of histological subtyping for pathologists. When the model was applied to whole-slide images, the predominant subtype according to the artificial intelligence model classification matched that determined by pathologists in 75.5% of cases. The predominant subtype and tumor grade (using the WHO fourth and fifth classifications) determined by the artificial intelligence model resulted in similar recurrence-free survival curves to those determined by pathologists. Furthermore, we stratified the recurrence-free survival curves for patients with different proportions of high-grade components (solid, micropapillary and cribriform) according to the physical distribution of the high-grade component. The results suggested that tumors with centrally located high-grade components had a higher malignant potential (P<0.001 for 5-20% high-grade component). The new artificial intelligence model for histological subtyping of lung adenocarcinoma achieved high accuracy, and subtype quantification and subtype distribution analyses could be achieved. Artificial intelligence model therefore has potential for clinical application for both quantification and spatial analysis.

Persistence comparison of two Shiga-toxin producing Escherichia coli (STEC) serovars during long-term storage and thermal inactivation in various wheat flours.

Foodborne outbreaks associated with Shiga toxin-producing Escherichia coli (STEC) contaminated wheat flour have been an increasing food safety concern in recent decades. However, there is little literature aimed at investigating the impact of different flour types on the persistence of STEC during storage and thermal inactivation. Therefore, two serovars of STEC, O121 and O157, were selected to inoculate each of five different types of common wheat flours: whole wheat, bleached, unbleached, bread, and self-rising. Inoculated flours were examined for the stability of STEC during storage for up to 42 days at room temperature (RT) and aw ~0.56. Additionally, the thermal resistance of O121 and O157 under isothermal conditions at 60, 70, 80, and 90°C was analyzed for the inoculated flours. STEC storage persistence at RT was generally not affected by flour type, however, decreases of 1.2 and 2.4 log CFU/day within whole wheat flour for O121 and O157, respectively, were significantly lower than other flours. Though few differences were identified in relation to flour type, O121 exhibited significantly better survival rates than O157 during both equilibrium and storage periods. Compared to an approximate 6 log reduction in the population of O157, O121 population levels were reduced by a significantly lower amount (~3 log) during the entire storage period at RT. At each isothermal temperature, the impact of flour type on the thermal resistance capabilities of O121 or O157 was not a significant factor and resulted in similar survival curves regardless of serovar. Instead of exhibiting linear survival curves, both O121 and O157 displayed nonlinear curves with some shoulder/tail effect. Similar for both O121 and O157, the predicted decimal reduction time (D-value) decreased from approximately 25 min to around 8 min as the isothermal temperature increased from 60°C to 90°C. Results reported here can contribute to risk assessment models concerning contamination of STEC in wheat flour and add to our understanding of the impacts of flour type and STEC serovar on desiccation stability during storage and isothermal inactivation during thermal treatment.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study

Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Life Span Changes of Coffee White Stem Borers, Xylotrechus quadripes (Coleoptera: Cerambycidae) in Response to Directed Homosexual and Heterosexual Interactions

Our study on coffee white stem borers, Xylotrechus quadripes investigated the influence of different sex-based clustering factors on beetle survivorship and life spans. Our experiments involved various groups, including individually isolated virgin males, individually isolated virgin females, groups of only males, groups of only females, and mixed-sex groups. First, survivorship reached 100% within the initial 15 days for all groups except for isolated virgin males. In contrast, the survivorship rates of both groups involving only virgin females and only virgin males ranged from 80% to 90% compared to the maximum survival duration. Notably, in scenarios with males in groups or mixed-gender groups, survival dropped to zero percent after 45 days. Our study also highlighted the comparable costs incurred by males engaging in both homosexual and heterosexual interactions. Males interacting with females and other males exhibited similar survival curves, displaying shorter median life spans compared to isolated virgin males, suggesting that both courting and mounting behaviors, regardless of the recipient's sex, might affect the life span of males. Furthermore, our research revealed that female-female interactions, while less costly than male-male interactions, still reduced survival periods in only the female group. These findings highlight the cost possibly associated with same-sex interactions and shed light on the dynamics of mating behaviors in this beetle. In conclusion, our findings underscore the significance of studying behavioral and life history traits in different environmental contexts. Social circumstances and ecological factors significantly influence sexual differences in lifespan and highlight the complexity of the interplay between reproductive strategies and survival rates in Xylotrechus quadripes.

Does discontinuing bleomycin due to toxicity increase the risk of lymphoma progression? Real-life data from a homogeneous population of advanced stage Hodgkin lymphoma

Hodgkin Lymphoma (HL) is often curable with ABVD therapy and improving outcomes is a main goal of ongoing research. Bleomycin-associated pneumonitis (BAPT) is a potentially life-threatening complication that necessitates bleomycin discontinuation. We conducted this study on a homogenous cohort of advanced stage HL treated only with ABVD for frontline therapy to assess if bleomycin discontinuation increases the risk of lymphoma progression. After the exclusion of patients who received radiotherapy or other drugs, 106 and 28 patients in the six-cycle ABVD and BAPT groups respectively had similar survival curves for progression and death with a 49-month median follow-up. PFS rates were also very similar at two and four years from diagnosis with 2-year PFS rates of 83.9% and 82.1% (RR = 1.1 95%CI = 0.45–2.2). Outcome comparisons were also similar between the two groups when stratified according to early response assessment with PET/CT. Patients who discontinued bleomycin due to toxicity did not experience an increased risk of progression compared to patients who completed six ABVD cycles.

Benefit of TKI-Treatment in CML after Failing Molecular or Cytogenetic Milestones

No information is available on long-term survival of tyrosine kinase inhibitor (TKI)- treated patients failing the response milestones as defined by the European LeukemiaNet (ELN). Such information would help with decision making in failing patients when risks associated with comorbidities, drug toxicities or transplantation preclude switching to another TKI or other treatments. To systematically analyze survival after reaching, or not reaching, ELN-response milestones, 1342 imatinib-treated patients from CML-study IV with newly diagnosed CML in chronic phase and regular molecular and cytogenetic tests were studied. Survival was analyzed by landmark analyses at 3, 6, 12 and 24 months and followed up to 14 years. In patients who failed the failure milestones (&amp;gt;10% BCR::ABL1 IS at 6 months, &amp;gt;1% BCR::ABL1 IS at 12 months), 10- to 12-year survival ranged around 70%, 10-20% less than in responding patients. An example is shown in Fig. 1a which depicts survival of patients reaching, or not reaching 1% BCR::ABL1 IS at 12 months. Similar survival curves were observed for the other landmarks that indicate failure. Inbetween response rates of &amp;gt;1%-10% BCR::ABL1 IS at 12 months indicated survival probabilities similar to those of patients failing 1% BCR::ABL1 IS, whereas patients reaching &amp;gt;1%-10% BCR::ABL1 IS at 24 months showed a survival similar to that of patients failing 10% BCR::ABL1 IS. Switching to alternative therapies, mostly to dasatinib and nilotinib, was observed in 372 patients (26.9%) and did not change the main results. Although cytogenetic tests were increasingly replaced by molecular tests in the course of the study, sufficient cytogenetic analyses were available for comparison with molecular analyses. Complete and partial cytogenetic remissions have been shown to be roughly equivalent to 1% and 10% BCR::ABL1 IS, respectively. Wheras reaching, or not reaching cytogenetic and molecular reponse markers at 6 and 12 months was equivalent, not reaching a complete or partial cytogenetic remission at 24 months identified a small subgroup of patients (5.9%) with inferior survival (Fig. 1b). Age (more or less than 60 years) had no major impact on survival differences, but on hazard ratios for early death. Hazard ratios at 10% BCR::ABL1 IS by 6 months were 4.0 (95%CI:2.0-8.1) for the younger patients, but only 0.9 (95% CI: 0.4-1.8) for the elderly. The reasons for early death in the younger patients were mostly CML-related, whereas the elderly primarily died of other reasons. The data show that TKI-treated patients not reaching failure milestones still may derive benefit from continuing TKI-treatment and provide a basis for individualized decisions, if failing patients are confronted with risks of alternative treatments.

Complication Rates and Survival of Nonagenarians after Hip Hemiarthroplasty versus Proximal Femoral Nail Antirotation for Intertrochanteric Fractures: A 15-Year Retrospective Cohort Study of 113 Cases.

Intertrochanteric fracture is a very common but serious type of hip fracture in nonagenarians. The surgical treatment remains a significant challenge for orthopedists. The objective of this study was to investigate postoperative complications and survival outcomes compared between bipolar hemiarthroplasty (HA) and proximal femoral nail anti-rotation (PFNA) in nonagenarians with intertrochanteric fractures, and to evaluate the efficacy and safety of the two surgical procedures in this patient population. A total of 113 consecutive nonagenarians who underwent bipolar HA or PFNA for the treatment of intertrochanteric fractures from January 2006 to August 2021 were retrospectively studied in the current paper. There were 34 males and 79 females, with a mean age of 92.2 years (range 90-101 years) at the time of operation. The average duration of follow-up was 29.7 months (range 1-120 months). The full cohort was divided into bipolar HA (77 cases) and PFNA (36 cases) groups. Damage control orthopedics was used to determine the optimal surgery time and assist in perioperative management. A restrictive blood transfusion strategy was employed, along with appropriate adjustments under multidisciplinary assessment, throughout the perioperative period. Perioperative clinical information and prognostic data were analyzed. Kaplan-Meier survival curves were used for survival analysis, and landmark analysis divided the entire follow-up period into 1-12 months (short-term), 13-42 months (medium-term) and 43-120 months (long-term) according to the configurations of Kaplan-Meier survival curves. Both groups had similar general variables except for the proportion of high adjusted Charlson comorbidity index (aCCI) (≥6 points) (6.5% in bipolar HA group and 22.2% in PFNA group, p = 0.024). Intraoperative blood loss and transfusion requirements were greater, and the intraoperative transfusion rates were higher in the bipolar HA group compared to the PFNA group (all p < 0.05). The complications rates, 1- to 60-month cumulative all-cause mortality, postoperative optimal Harris hip score (HHS), and Barthel index (BI) presented no significant difference between the two groups (all p > 0.05). Both groups had similar overall survival curves (p = 0.37). However, landmark analysis revealed that bipolar HA group exhibited higher survival rates in medium-term (p = 0.01), while similar survival rates were observed in the short- and long-term post-operation periods (both p > 0.05). Cox regression with survival-time-dependent covariate calculated the hazard ratio (HR) of bipolar HA was 0.41 in medium-term (p = 0.039). Bipolar HA is equally effective and reliable as PFNA for treating intertrochanteric fractures in nonagenarians. Despite resulting in more intraoperative blood loss and transfusions, bipolar HA therapy is associated with a higher medium-term survival rate compared to PFNA treatment. The application of damage control orthopedics and precise perioperative patient blood management could contribute to the positive clinical outcomes observed in this patient population.

Participation in phase I oncology trials by minorities: Survival and compliance data.

e18628 Background: Since 1993, the National Institutes of Health requires all clinical trials to include women and minority participation in clinical research. Despite this initiative, Minority (M) participation in Phase I Oncology clinical trials is subpar; historical data indicate a participation of 79% Caucasian (C) versus 21% (M) in Phase I clinical trials. The purpose of this study is to compare demographics, survival, and compliance data between (C) versus (M) patients participating in Phase I Oncology clinical trials in our Cancer Institute. Methods: We performed a retrospective analysis in all patients enrolled in phase I clinical trials in our institution from April 2019 until October 2022. This information was obtained via OnCore. Data was abstracted manually and entered in a spreadsheet (Excel). Data variables include race, gender, withdrawal of consent, and lost follow-up. Statistical plan was determined by our statistical team with data analysis to be performed with statistical software to generate Kaplan Meyer (KM) Survival Curve. Results: A total of 99 patients were identified. 61.5% were (C) and 38.4 % were (M). (M) consisted of Hispanic (81%), African American (18%) and Asian (1%). Female Gender on (C) were 57.4% and 55.3% on (M). Lost follow-up was 2.8% on (C) and 5.9% on (M). Withdrawal of consent was 5.6% on (C) and 0% on M. The (KM) curve revealed non statistically significant difference in survival p = 0.7316. Conclusions: In our analysis, we found statistically similar (KM) survival curves for (C) and (M) participating in Phase I clinical trials (p = 0.7316). We found a significant higher participation of (M) patients in our institute than historical data. There was no significant difference in withdrawal of consent between (C) and (M) and no difference on lost follow-up. We plan to identify patterns of success in enrolling minorities in our site and validate a questionnaire to screen patients for Phase I clinical trials with the goal to minimize perception bias and barriers for enrollment of (M) in Phase I studies.

Impact of duration of mechanical support on heart transplantation: Hasty transplantation may not have a good long-term outcome.

Mechanical circulatory support (MCS) has been widely utilized in critically ill cardiac transplant candidates. Few studies have investigated the impact of duration of MCS before heart transplantation (HTx) on long-term patient survival. A retrospective HTx database was reviewed between 2009 and 2019. Patients who did not or did undergo MCS before HTx were categorized into two groups: (1) A (did not) and (2) B (did), respectively. A receiver operating characteristic (ROC) curve was plotted to assess the cutoff level of MCS duration before HTx in evaluating 5-year survival. A total of 270 HTx patients (group A: 120, group B: 150) were analyzed. Group B patients had a higher percentage of blood type O, a higher incidence of resuscitation, a shorter listing duration, and a higher likelihood of having United Network for Organ Sharing (UNOS) 1A status than group A. The ROC curve revealed 24 days as a good cut-off level for determining the best MCS before HTx timing. Group B was categorized into two subgroups: (1) B1 (MCS<24 days, n=65) and (2) B2 (MCS>24 days, n=85). B2 had a higher incidence of cardiopulmonary resuscitation (CPR), hemodialysis, longer waiting time after MCS, and better ventricular assist device implantation than B1. However, the survival curves showed that B1 outcomes were significantly worse than in groups A and B2. Groups A and B2 had similar survival curves without an increased incidence of infection. The preliminary data demonstrated that a longer duration of MCS may be associated with better outcomes than urgent HTx.

Survival of patients on chronic hemodialysis versus chronic peritoneal dialysis.

To compare the survival of patients with chronic kidney disease (CKD) on hemodialysis (HD) versus peritoneal dialysis (PD). Survival analysis of a retrospective cohort of patients ≥ 18 years who started HD versus PD at the Victor Lazarte Echegaray Hospital from 2015 to 2019. We analyzed the following covariates: age, sex, diabetes mellitus as cause of CKD, temporary central venous catheter (CVC) as initial vascular access and glomerular filtration rate. Survival was calculated with Kaplan-Meier curves for the overall cohort and for age ≥ 60 years, diabetes mellitus as a cause of CKD and CVC. The risk of death was estimated by Hazard Ratio (HR) according to the Cox proportional hazards model for each covariate adjusted for dialysis type in a bivariate and multivariate analysis considering significant difference if the p-value < 0.05. We included 368 patients on HD of whom 129 (35.1%) died, and 172 patients on PD of whom 66 (38.4%) died (p=0.455). The cumulative probability of survival at 60 months for HD was 30% and for PD was 37% with similar survival curves (p=0.719). The median survival time for HD was 32 months (IQR: 20-53) and for PD was 32.5 months (IQR: 18-57) (p=0.999). The covariates associated with higher mortality adjusted for dialysis type were age ≥60 years (HR 1.77; p<0.001) and diabetes mellitus as a cause of CKD (HR 1.63; p=0.002). Survival of patients with CKD on HD and PD was similar.

Drug Survival Associated With Effectiveness and Safety of Treatment With Guselkumab, Ixekizumab, Secukinumab, Ustekinumab, and Adalimumab in Patients With Psoriasis

Drug survival of biologic therapies for psoriasis is a proxy for longer-term treatment effectiveness and safety. Patient factors that are associated with the survival of each biologic differently (effect modifiers) may inform the decision to choose between biologics. To assess the drug survival associated with the effectiveness and safety of commonly used biologics for psoriasis in the UK and Ireland and identify effect modifiers for these biologics and their survival. We conducted a prospective cohort study of patients with psoriasis using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2021. Adalimumab, ustekinumab, secukinumab, guselkumab, ixekizumab. We conducted a survival analysis and fitted separate flexible parametric models for drug survival as a proxy for effectiveness and safety. A total of 16 122 treatment courses were included: 6607 (41.0%) in which treatment with adalimumab was initiated, 5405 (33.5%) with ustekinumab, 2677 (16.6%) with secukinumab, 730 (4.5%) with guselkumab, and 703 (4.4%) with ixekizumab. The crude survival functions at year 1 for measures of effectiveness for treatment with adalimumab was 0.81 (95% CI, 0.80-0.82), 0.89 for ustekinumab (95% CI, 0.88-0.89), 0.86 for secukinumab (95% CI, 0.85-0.87), 0.94 for guselkumab (95% CI, 0.92-0.96), and 0.86 for ixekizumab (95% CI, 0.83-0.89). The adjusted survival curves from the multivariable model for effectiveness showed that treatment with guselkumab had the higher survival (adjusted hazard ratio, 0.13; 95% CI, 0.03-0.56) and adalimumab had the lower survival (adjusted hazard ratio, 2.37; 95% CI, 2.03-2.76) compared with ustekinumab. Secukinumab and ixekizumab had similar survival curves over time. Psoriatic arthritis, previous biologic exposure, nail involvement, and ethnicity were effect modifiers for survival in association with treatment effectiveness. The crude survival functions at year 1 for safety were 0.91 for treatment with adalimumab (95% CI, 0.90-0.91), 0.94 for ustekinumab (95% CI, 0.94-0.95), 0.94 for secukinumab (95% CI, 0.92-0.94), 0.96 for guselkumab (95% CI, 0.94-0.98), and 0.92 for ixekizumab (95% CI, 0.89-0.94). Guselkumab, ustekinumab, and secukinumab had similar adjusted survival curves for safety, while adalimumab (adjusted hazard ratio, 1.66; 95% CI, 1.46-1.89) and ixekizumab (adjusted hazard ratio, 1.52; 95% CI, 1.13-2.03) had lower survival compared with ustekinumab. The results of this cohort study suggest that guselkumab had the highest drug survival in BADBIR of the included biologics for treatment persistence that was associated with effectiveness, and guselkumab had highest drug survival for safety compared with other biologics except ustekinumab. Psoriatic arthritis, nail involvement, previous biologic exposure, and ethnicity were effect modifiers for biologics and their survival in association with treatment effectiveness. This information on longer-term treatment persistence, safety, and tolerability may help patients and their clinicians make an informed decision to initiate treatment with a biologic therapy.

Comparison of Oncologic Outcomes Between Incomplete Obstructive Colon Cancer and Non-Obstructive Colon Cancer by Tumor Location.

IntroductionObstruction in colon cancer is a well-known risk factor for worse oncologic outcomes. However, studies on differences in survival of patients with incomplete obstructive colon cancer (IOCC) by tumor location are insufficient. Thus, the aim of this study was to compare oncologic outcomes between IOCC and non-obstructive colon cancer (NOCC) according to tumor location.MethodsFrom January 2010 to December 2015, a total of 2,004 patients diagnosed with stage II or stage III colon adenocarcinoma who underwent elective colectomy were included (IOCC, n = 405; NOCC, n = 1,599). Incomplete obstruction was defined as a state in which colonoscopy could not pass through the cancer lesion but did not require emergent surgery, stent insertion, or stoma formation because the patient was asymptomatic without problem in bowel preparation. Kaplan–Meier method and log-rank tests were used to compare survival between IOCC and NOCC. Multivariable analysis was performed to determine which factors affected survivals.ResultsStage III IOCC patients showed significantly lower overall survival (OS) and recurrence-free survival (RFS). Stage II IOCC patients and stage III NOCC patients had similar survival curves. IOCC patients with tumors on the right side showed worse OS than other patients. In multivariable analysis, incomplete obstruction was an independent risk factor for worse OS and RFS in all stages. Tumor located at the right side in stage III was an independent risk factor for RFS (HR: 1.40, p = 0.030).ConclusionsPatients with IOCC showed significantly worse survival outcomes than those with NOCC. Stage II IOCC patients and stage III NOCC patients showed similar survival. Patients with stage III IOCC located at the right side showed significantly worse oncologic outcomes than those located at the left side. These results confirm that prognosis is different depending on the presence of incomplete obstruction and the location of the tumor, even in the same stage.

Survival After Lung Transplantation is Conditional to Bronchial Complications

<h3>Purpose</h3> Bronchial complications (BC) following lung transplant have a significant impact on morbidity and mortality. The published incidence of bronchial complications varies between 2 and 18%. This study was undertaken to analyse our experience with BC following lung transplantation in first 300 patients at our unit. <h3>Methods</h3> A retrospective analysis of our first 300 lung transplant recipients from 1993 to 2019 was undertaken with regards to BC. Recipient and donor-specific risk factors were analysed. Patients were divided into two groups: Group A, with and Group B, without BC. A <i>p</i> value of < 0.05 was considered statistically significant with statistical analysis performed using SAS v9.4. Graft salvage was achieved in a small subset of patients. <h3>Results</h3> 47 patients (15.6%) developed BC. On univariate analysis, recipient risk factors predictive of bronchial complications were male sex, age, a diagnosis of cystic fibrosis and Alpha 1 antitrypsin deficiency, respiratory colonisation and prolonged post-operative ventilation. Male donors posed higher risk. However, on stepwise multivariate logistic regression analysis, only recipient male gender, recipient age, and prolonged ventilation were significant. The median follow-up was 6.2 years. The survival rates were 93.4%, 87.4%, 83.2%, and 53.8% at 30 days, 90 days, 1 year, and 5 years respectively. The median survival varied, was 3.9 years (Group A) and 6.2 years (Group B).The 30 day, 90-day, 1-year and 5-year actuarial survival rates were significantly lower for recipients with bronchial complications. Patients with BC had twice the mortality within one year. BC contributed to early mortality and similar long term survival curves for those with and without BC. <h3>Conclusion</h3> Development of major bronchial complications is one of the important factors in determining morbidity and survival following lung transplantation. However, the conditional survival following three months after surgery is similar and early intervention may prolong survival.

Reclassifying pT3 renal pelvic urothelial carcinoma with renal parenchyma invasion to pT2 improves correlation with overall survival

The American Joint Cancer Committee pT categorization in renal pelvic carcinoma defines pT3 as invasion of renal parenchyma, invasion of peripelvic fat, or both. However, survival heterogeneity within the pT3 category has been demonstrated. This investigation sought to compare survival between pT categories of renal pelvic urothelial carcinoma and identify modifications to improve correlation with survival. Pathology reports from nephroureterectomies performed at our institution from 2010 to 2019 were analyzed to identify primary renal pelvic urothelial carcinoma (n=146). Tumors were stratified based on pT, pN, and invasion of renal parenchyma vs invasion of peripelvic fat with or without renal parenchyma invasion. Kaplan-Meier survival curves and Cox regression multivariate analysis were used to compare overall survival between groups. Similar survival curves were observed for pT2 and pT3 tumors. Multivariate analysis confirmed overlapping hazard ratios (HRs) for pT2 (HR=2.64, 95% confidence interval [CI] = 0.69, 10.06)and pT3 (HR=4.42, 95% CI = 2.08, 9.37). pT3 tumors with peripelvic fat invasion, regardless of renal parenchyma involvement, had a 3.3-fold worse overall survival than pT3 tumors with only renal parenchyma involvement. Additionally, pT3 tumors with only renal parenchyma invasion had similar survival compared to pT2, while pT3 tumors with peripelvic fat invasion had worse overall survival (p=0.00091). Reclassifying renal parenchyma invasion as pT2 yielded greater survival curve separation and greater difference in HRs. For renal pelvic urothelial carcinoma, modifying the pT3 category to only include tumors with peripelvic fat invasion and expanding the pT2 category to include renal parenchyma invasion may improve pT correlation with overall survival.

Recombinant BCG Expressing the Subunit 1 of Pertussis Toxin Induces Innate Immune Memory and Confers Protection against Non-Related Pathogens.

BCG has shown the ability to induce protection against unrelated pathogens, which likely depends on an immune mechanism known as innate immune memory or trained immunity. In this study, we evaluated the induction of innate memory by a recombinant BCG strain expressing the genetically detoxified S1 subunit of the pertussis toxin (rBCG-S1PT). In vitro pre-exposure of naïve murine macrophages to rBCG-S1PT increased their innate/inflammatory response (IL-6, TNF-α, and IL-10) to a subsequent challenge with unrelated pathogens, as compared to pre-exposure to wild-type BCG. Following LPS challenge, mice immunized with rBCG-S1PT produced higher levels of IFN-γ, while the release of other inflammatory cytokines was comparable to that measured after BCG immunization. SCID mice previously immunized with rBCG-S1PT and challenged with pathogenic Candida albicans displayed a similar survival curve as BCG-immunized mice but a lower CFU burden in the kidneys, suggesting an innate memory-dependent control of C. albicans infection. This study highlights the potential of recombinant BCG to increase innate immune memory and, ultimately, non-specific protection, more effectively than wild-type BCG. To our knowledge, this is the first report describing the potential of a recombinant BCG strain to strengthen innate immune memory responses.

Prophylactic versus therapeutic dose anticoagulation effects on survival among critically ill patients with COVID-19.

Although patients with severe COVID-19 are known to be at high risk of developing thrombotic events, the effects of anticoagulation (AC) dose and duration on in-hospital mortality in critically ill patients remain poorly understood and controversial. The goal of this study was to investigate survival of critically ill COVID-19 patients who received prophylactic or therapeutic dose AC and analyze the mortality rate with respect to detailed demographic and clinical characteristics. We conducted a retrospective, observational study of critically ill COVID-19 patients admitted to the ICU at Stony Brook University Hospital in New York who received either prophylactic (n = 158) or therapeutic dose AC (n = 153). Primary outcome was in-hospital death assessed by survival analysis and covariate-adjusted Cox proportional hazard model. For the first 3 weeks of ICU stay, we observed similar survival curves for prophylactic and therapeutic AC groups. However, after 3 or more weeks of ICU stay, the therapeutic AC group, characterized by high incidence of acute kidney injury (AKI), had markedly higher death incidence rates with 8.6 deaths (95% CI = 6.2-11.9 deaths) per 1,000 person-days and about 5 times higher risk of death (adj. HR = 4.89, 95% CI = 1.71-14.0, p = 0.003) than the prophylactic group (2.4 deaths [95% CI = 0.9-6.3 deaths] per 1,000 person-days). Among therapeutic AC users with prolonged ICU admission, non-survivors were characterized by older males with depressed lymphocyte counts and cardiovascular disease. Our findings raise the possibility that prolonged use of high dose AC, independent of thrombotic events or clinical background, might be associated with higher risk of in-hospital mortality. Moreover, AKI, age, lymphocyte count, and cardiovascular disease may represent important risk factors that could help identify at-risk patients who require long-term hospitalization with therapeutic dose AC treatment.

Prevention of Acute Graft-Versus-Host Disease Using an Engineered Mouse Orthogonal IL-2/IL-2Rβ Regulatory T Cells

Regulatory T cells are a critical population for the maintenance of self-tolerance and the use of these cells for therapeutic purpose in transplantation has emerged based on their capacity to control immune activation, exhibiting positive therapeutic potential to ameliorate acute graft-versus-host disease (GvHD), one of the major complications after allogeneic bone marrow transplantation (allo-BMT). One of the remaining technical challenges in the clinical practice of Treg administration is the number of Treg required to effectively prevent GvHD. In this study, we engineered murine Treg cells to express an altered IL-2 receptor β subunit that selectively interacts with an orthogonal mutant IL-2 (oIL2) without interacting with the natural cytokine or receptor counterparts, thus preventing acute -GvHD.For investigation of the suppressive function of Treg orthogonal IL-2/IL-2 receptor system in a murine major mismatch of acute GvHD model, the BALB/c mice were lethally irradiated (8.8 Gy) and transplanted with 5x10 6 T cell-depleted bone marrow cells (TCD-BM) from C57Bl/6 mice alone or together with fresh 1x10 6 C57Bl/6 FoxP3 DRT-GFP-luc+ Treg cells (fTreg) or with 0.2x10 6 and 1x10 6 oTreg (transduced with the construct for murine oIL-2 receptor β chain) on day 0. On day 2, C57Bl/6 Tcon cells (1x10 6) were injected to induce GvHD. Recipients were treated with PBS or oIL-2 (25K IU/daily) for 14 days and then 3 times a week for another 14 days.Using bioluminescence imaging, we observed that ortho IL2Rβ +Treg not only maintains migration ability to the gut, mLN and LN but also exhibited significant expansion ability treated with oIL2 at day 7 post-transplant. The expansion of oTreg with PBS and fTreg was observed on day 14 after allo-BMT. The administration of oTreg-oIL2 and fTreg (1:1 Tcon:Treg ratio) significantly increased the survival of the mice compared to Tcon group (P<0.0001 and P=0.0001, respectively). Furthermore, the group oTreg-oIL2 (1:1) showed a significant increase in the survival curve compared to the fTreg group (P=0.03). When decreasing the number of oTreg administrated (5:1 Tcon:Treg ratio) a significant increase in the survival (Tcon vs Tcon:oTreg (5:1)+oIL2; P<0.0001) in the oIL2 group. Similar survival curves were observed between this group and fTreg group (1:1).oIL-2 protein injection was able to selectively expand the oTreg in vivo, with a significantly increased percentage of Foxp3 GFP+ in CD4 + T cells (PBS;14.96±2.4%, oIL-2; 27.76±23.6%, P=0.02) in the peripheral blood (PB) and spleen after 7 days post-transplant. We also observed a significant decrease in the percentage of effector T cells in the LN, mLN and spleen of the mice transplanted with oTreg and oIL-2 administration after 7 days post transplantation compared with GvHD group. We further demonstrated that ortho-IL2 administration-maintained graft-versus-leukemia (GvL) responses against lymphoma cells (A20).Engineered orthogonal cytokine receptor improves the suppressing abilities of Treg potential in a murine model of acute GvHD with the ability to maintain GvL, representing a novel approach to the utilization of Treg in Allogeneic Hematopoietic Stem Cell Transplant. DisclosuresGarcia: Synthekine: Membership on an entity's Board of Directors or advisory committees. Blazar: Tmunity Therapeutics: Other: Co-founder; Equilibre Pharmaceuticals Corp: Research Funding; Carisma Therapeutics, Inc: Research Funding; Rheos Medicines: Research Funding; BlueRock Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Perineural Invasion Should Be Regarded as an Intermediate-Risk Factor for Recurrence in Surgically Treated Cervical Cancer: A Propensity Score Matching Study.

Background Perineural invasion (PNI) is considered as a poor prognostic factor in cervical cancer, but there has been no postoperative adjuvant therapy for it, because whether it belongs to high- or intermediate-risk factors has not been determined, this study intends to provide evidences to solve this problem. Methods We conducted a retrospective analysis of cervical cancer patients who underwent radical surgery and be reported PNI from January 2012 to June 2017 at the Sun Yat-sen University Cancer Center. After 1 : 1 propensity score matching (PSM), a group of patients without PNI was matched according to the clinical pathological features. Postoperative pathological parameters and prognosis were evaluated between the PNI and the matched groups. Results 1836 patients were screened, of which 162 (8.8%) diagnosed as stages IB1 to IIB reported PNI. Comparing to the matched group, more PNI (+) patients had deep outer cervix stromal invasion, cervical tunica adventitia invasion, positive lymph nodes, and positive margins. Among patients without high-risk factors, PNI (+) patients had worse 3-year overall survival (90.8% vs. 98.1%, P = 0.02), PNI (+) patients with single intermediate-risk factor and PNI (-) patients who meet with SEDLIS criteria had similar progress free survival (P = 0.63) and overall survival (P = 0.63), even similar survival curves. Conclusion PNI is related to a worse overall survival among cervical cancer patients without high-risk factors and play the role as an intermediate-risk factor.

Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia

BackgroundTrauma and sepsis are individually two of the leading causes of death worldwide. When combined, the mortality is greater than 50%. Thus, it is imperative to have a reproducible and...