Estimated Survival Rates Research Articles

Killer whale (Orcinus orca) population dynamics in response to a period of rapid ecosystem change in the eastern North Atlantic.

This study investigates survival and abundance of killer whales (Orcinus orca) in Norway in 1988–2019 using capture–recapture models of photo‐identification data. We merged two datasets collected in a restricted fjord system in 1988–2008 (Period 1) with a third, collected after their preferred herring prey shifted its wintering grounds to more exposed coastal waters in 2012–2019 (Period 2), and investigated any differences between these two periods. The resulting dataset, spanning 32 years, comprised 3284 captures of 1236 whales, including 148 individuals seen in both periods. The best‐supported models of survival included the effects of sex and time period, and the presence of transients (whales seen only once). Period 2 had a much larger percentage of transients compared to Period 1 (mean = 30% vs. 5%) and the identification of two groups of whales with different residency patterns revealed heterogeneity in recapture probabilities. This caused estimates of survival rates to be biased downward (females: 0.955 ± 0.027 SE, males: 0.864 ± 0.038 SE) compared to Period 1 (females: 0.998 ± 0.002 SE, males: 0.985 ± 0.009 SE). Accounting for this heterogeneity resulted in estimates of apparent survival close to unity for regularly seen whales in Period 2. A robust design model for Period 2 further supported random temporary emigration at an estimated annual probability of 0.148 (± 0.095 SE). This same model estimated a peak in annual abundance in 2015 at 1061 individuals (95% CI 999–1127), compared to a maximum of 731 (95% CI 505–1059) previously estimated in Period 1, and dropped to 513 (95% CI 488–540) in 2018. Our results indicate variations in the proportion of killer whales present of an undefined population (or populations) in a larger geographical region. Killer whales have adjusted their distribution to shifts in key prey resources, indicating potential to adapt to rapidly changing marine ecosystems.

Effects of a Domino Liver Transplantation Program on Patient Survival and Waiting List Time: A Single-Center Retrospective Study

Explanted livers from patients with familial amyloid polyneuropathy have often been used for domino liver transplantation (DLT). This has expanded the organ pool for liver transplantation. We evaluated the effects of a single-center DLT program on waiting list duration and patient survival. Liver transplants conducted from 2007 to 2017 were analyzed. Selected patients, all liver transplant candidates above the age of 60 years and patients with hepatocellular carcinoma, were offered DLT. Survival, time on waiting list, and operative factors were evaluated. The study group included 485 patients transplanted with grafts from deceased donors (conventional liver transplantation) and 149 patients who were offered and accepted a potential DLT, of whom 34 underwent DLT and 115 did not; these patients received a deceased donor graft (non-DLT). Five-year and overall estimated survival rates respectively were 79% and 54.4% for DLT and 67.6% and 46.7% for non-DLT (P=.67, log rank test). No differences were noted in survival (P=.816) or waiting times (P=1.0) between DLT and non-DLT groups. As expected, survival time in the conventional liver transplantation group was longer (84.7% and 60.6%, P < .001). Donor age and ischemia time were significantly different between DLT and non-DLT (P < .001). DLT has enabled 6% additional transplantations without affecting waiting time or survival (34/600).

The Impact of COVID-19 on Acute Myeloid Leukemia (AML) Treatment Patterns in the United States: Retrospective Analysis of an Electronic Medical Records (EMR) Database

INTRODUCTION: COVID-19 has disrupted healthcare access for patients (pts) with cancer, which may pose an especially high risk for pts with hematologic malignancies (NCI, 2021). The standard of care for newly diagnosed (ND) AML is induction with intensive chemotherapy (IC; “7+3”) ± consolidation for eligible pts; while during the COVID era, lower-intensity regimens, such as a hypomethylating agent (HMA) plus venetoclax (VEN), may be recommended over 7+3 to eligible pts to minimize transfusions and inpatient hospitalizations. For pts who achieved remission from induction, COVID-19 may have led some practitioners to reduce the number of consolidation cycles and/or lower the cytarabine dose used for consolidation. Transplantation, including hematopoietic stem cell transplantation (HSCT), has been severely impacted (even halted in some areas) during COVID-19 (NasrAllah, 2021). The influence of COVID-19 on AML treatment (Tx) and outcomes has yet to be adequately studied.OBJECTIVE: To assess the impact of COVID-19 on AML Tx patterns and survival in the real-world practice setting.METHODS: The Flatiron™ EMR database was used in this retrospective analysis of US pts aged ≥ 18 years with an AML diagnosis between 1 Jan 2018 and 31 Jan 2021 and who had ≥ 2 months of follow-up. Tx patterns and survival outcomes were compared between a Pre-COVID cohort, defined as pts diagnosed with AML between 1 Jan 2018 and 31 Dec 2019, and a Post-COVID cohort of pts diagnosed between 1 Mar 2020 and 31 Jan 2021. Pt characteristics and Tx patterns were assessed for all pts and in the Pre- and Post-COVID cohorts using summary statistics. Time to event analyses used Kaplan-Meier methods for survival curves and were compared by log-rank tests.RESULTS: In all, 2,133 pts met the selection criteria (mean age was 66.0 years, 57.5% were male, and 75.7% were treated in community practices); 1,582 (74.2%) pts were in the Pre-COVID cohort and 551 (25.8%) were in the Post-COVID cohort. Pt characteristics were generally similar between cohorts.In the Post-COVID cohort, use of IC and HMA-only induction decreased significantly, while induction with VEN + an HMA increased (Fig. A): 29.4% of pts (n=132) in the Post-COVID cohort received VEN + azacitidine and 19.8% (n=89) received VEN + decitabine, compared with 16.0% (n=190) and 9.0% (n=107), respectively, in the Pre-Covid cohort (P < 0.001, both comparisons). Time to induction was shorter in the Post-COVID cohort vs the Pre-COVID cohort (median 14 vs 18 days; P < 0.001).In all, 1,056 pts attained remission within 180 days of induction, including 774 Pre-COVID and 282 Post-COVID pts. Among them, 621 pts had a follow-up period of ≥ 180 days (394 pts Pre-COVID, 227 pts Post-COVID) and 41.1% (n=162) vs. 14.1% (n=32) of pts in the Pre- and Post-COVID cohorts, respectively, received consolidation (P < 0.001). Proportions of pts receiving maintenance therapy (MT) were 23.9% (n=94) and 17.6% (n=40) in the Pre- and Post-COVID cohorts, respectively (P = 0.069).Time to HSCT was significantly increased for pts in the Post-COVID cohort (P = 0.035; Fig. B), and rate of HSCT was reduced for Post-COVID pts vs Pre-COVID pts (19.0% vs 13.3%, respectively, at 180 days, and 31.3% vs 22.7% at 360 days). Estimated overall survival (OS) was significantly longer in the Pre-COVID cohort (P = 0.006 vs. Post-COVID); at 360 days of follow-up, estimated survival rates in the Pre- and Post-COVID cohorts were 68.3% vs. 51.3%, respectively.CONCLUSIONS: Induction with IC and HMAs was less frequent for pts diagnosed with AML during COVID-19, while induction with VEN + an HMA increased in these pts. Use of consolidation significantly decreased during COVID-19, and use of MT also decreased. These changes may have been influenced by inpatient resource constraints. Compared with the Pre-COVID cohort, Post-COVID pts were significantly less likely to receive HSCT, and longer HSCT waiting times suggest the pandemic affected access to timely transplantation, potentially due to hospital policies limiting surgeries, lack of available inpatient beds, or donor reluctance to visit a hospital during the pandemic. OS and 1-year survival were compromised in the Post-COVID cohort vs Pre-COVID pts, likely due to COVID-19 infection, but perhaps in part due to constraints on access to healthcare resources. These data suggest a need for oral Tx that can prolong remission while reducing clinic and inpatient visits, and that can bridge the gap until HSCT. [Display omitted] DisclosuresChen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Rotter: SmartAnalyst Inc.: Current Employment. Potluri: Bristol Myers Squibb: Consultancy.

Prognostic Value of Myocardial Enzymes and Therapeutic Potential of Cardioprotective Agents in Chronic Lymphocytic Leukemia Patients with Cardiovascular Comorbidities

Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in the western world. Cardiovascular disease (CVD), with a high incidence among comorbidities, is associated with significant morbidity and inferior quality of life in cancer patients. In CLL, comorbidities are associated with increased mortality from infections, second cancers and CVD. However, previous studies have not uncovered the relationships between cardiac biomarkers and the prognosis of CLL patients. In addition, whether cardioprotective drugs affect the effect of therapy in CLL patients remains undefined.Methods: Five hundred and ten CLL patients diagnosed in Shandong Provincial Hospital affiliated to Shandong University from October 2010 to July 2020 were enrolled in our study. The Kaplan-Meier curves were used to estimate survival rates, while the log-rank tests were used for comparison. Univariate and multivariate logistic regression analysis was used to verify prognostic independence. The available expression data and survival information of CLL samples and normal samples were extracted from 2 databases. The expression level of genes involved in the KEGG lipid and atherosclerosis pathway was analyzed to evaluate the prognosis of CLL patients. GSEA enrichment analysis was performed to explore the potential function of TNFRSF1A. Cell proliferation assay with the Cell Counting Kit-8 (CCK-8) was performed to detect the therapeutic potential of the common cardioprotective drugs atorvastatin, metoprolol and losartan in CLL.Results: Among the cohort, 30% CLL patients were complicated with CVD. Compared with those without CVD, CLL patients with CVD were of significantly advanced age (p<0.001), larger proportion with diabetes (p=0.003), as well as higher levels of N-terminal brain natriuretic peptide precursor (NTpro-BNP; p=0.016) and myohemoglobin (MYO; p=0.005). The Kaplan-Meier curves revealed that Binet stage (χ2=3.863, p=0.049), creatine kinase isoenzyme (CK-MB; χ2=4.335, p=0.037) and MYO (χ2=4.010, p=045) were related to the OS time of CLL patients with CVD (shown in Figure 1). The univariate logistic analysis showed that sex (p=0.031), Rai stage (p=0.036), Binet stage (p=0.017), β2-MG (p=0.004), creatine kinase (CK; p=0.017), α-hydroxybutyrate dehydrogenase (α-HBDH; p=0.017), MYO (p=0.025) and C-reactive protein (p=0.007) were associated with the outcomes of CLL patients with CVD. The multivariate logistic analysis confirmed that α-HBDH (p=0.046) and MYO (p=0.013) were independent prognostic biomarkers for the outcomes of CLL patients with CVD.To further evaluate the prognosis of CLL patients and CVD, the expression of genes involved in the KEGG lipid and atherosclerosis pathway were assessed. Most of them were dysregulated (shown in Figure 2A-B). The genes which were differential expression were performed with Kaplan-Meier analysis and univariate and multivariate Cox analysis subsequently. TNFRSF1A was upregulated among CLL cells and was independent prognostic biomarkers of both OS (shown in Figure 2C) and time to first treatment (TTFT) in CLL patients (shown in Figure 2D). GSEA enrichment illuminated that TNFRSF1A was related to the lipid catabolic and metabolic process, as well as other metabolic processes (shown in Figure 2E-F).To investigate the effect of cardioprotective drugs on chronic lymphocytic leukemia patients, cell proliferation assays were performed. Atorvastatin, metoprolol and losartan decreased the proliferation of CLL cell lines with IC50 values of 94.19 uM, 123.60 uM and 411.80 uM in EHEB cells, and 79.20 uM, 138.60 uM and 318.5 uM in MEC-1 cells, respectively (shown in Figure 3).Conclusions: In conclusion, we demonstrated CLL patients with CVD were of older age, larger proportion of patients with diabetes, higher levels of NTpro-BNP and MYO compared those without CVD for the first time. α-HBDH and MYO were independent prognostic biomarkers for survival in CLL patients with CVD. TNFRSF1A was an independent prognostic biomarker of OS and TTFT in CLL patients. Furthermore, atorvastatin, metoprolol and losartan exhibited inhibitory effects in CLL cell lines. The evaluation of cardiac biomarkers is beneficial to predict the clinical outcomes of CLL patients. CLL patients may benefit from the application of cardioprotective agents. Strengthening the evaluation of CVD risk and preventing CVD may improve the prognosis of CLL patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Amazon river dolphinsInia geoffrensisare on the path to extinction in the heart of their range

AbstractRiverine cetaceans are threatened globally by increasing anthropogenic impacts, and the Yangtze river dolphinLipotes vexilliferis already extinct. The Amazon river dolphinInia geoffrensisis widely distributed, but is categorized as Endangered on the IUCN Red List. Drowning in gillnets and being hunted for fish bait are probably the main causes of its decline. A long-term (25-year) study of the biology and ecology ofI. geoffrensisin and near the Mamirauá Reserve in Amazonas state, Brazil, has produced estimates of survival and reproductive rates based on the individual recognition of &gt; 650 animals. Concurrently, monthly standardized counts of dolphins along a fixed transect in the Reserve over 22 years demonstrated a sustained, profound decline. In this study we tested whether the measured rate of population decline is consistent with population parameters estimated from independent data, using population viability analysis. With the known parameters as input, programmeVortexpredicted population extinction in all scenarios and a 95% loss of dolphins within 50 years. With default parameters, the model predicted a 5.5% annual decline, which is consistent with that observed. We conclude that the Amazon river dolphin population is in severe decline because of human pressures, even in one of the better protected parts of its range. Unless the accidental and deliberate killing of this species is rapidly reduced, it is highly likely that the Amazon river dolphin will follow its Yangtze counterpart to extinction.

Review and Synthesis of Estimated Vital Rates for Terrestrial Salamanders in the Family Plethodontidae

Population models depend on reliable estimates of vital rates, yet for many taxa, such estimates and how they vary in response to spatial or temporal environmental gradients are lacking. The goal of this review was to determine whether existing estimates of vital rates for temperate, direct-developing plethodontid salamanders (subfamily Plethodontinae) could be used to reasonably project values for populations or species where such estimates are lacking, or whether current estimates are biased in a manner that limits their utility. We synthesized current knowledge of stage-specific survival rates, age- and size-at-maturity at first clutch, and clutch frequency. We tested for expected correlations among published vital rates (e.g., age at maturity and survival) and between vital rates and factors such as body size or latitude. We used matrix projection models to judge whether published estimates were reasonably possible for stable salamander populations. The largest number of published vital rates were for clutch size, clutch frequency (proportion of females with clutches), size at maturity or first clutch, and age at maturity or first clutch, though the latter vital rate is primarily inferred from size distribution and growth rate data. Among these vital rates, we found expected correlations with body size and latitude suggesting these rates were reasonable and somewhat predictable among species or populations. In contrast, there were few estimates of egg hatch rate or juvenile or adult survival. Hatch and survival rate estimates were widely variable; estimates seldom included measures of uncertainty, but when uncertainty measurements were included, they were generally high. Based on projection models, few survival estimates were likely unbiased or realistic for stable populations given other salamander vital rates. Additionally, few studies quantified how vital rates vary with spatial or temporal environmental gradients. We outline the key knowledge gaps that limit basic demographic modeling of these remarkably common, influential, and otherwise well-studied salamanders, and make recommendations for future research efforts.

Disparities between perceived and true outcomes of infants born at 23-25 weeks' gestation.

Decision-making for infants born at 23-25weeks involves counselling parents about survival and major disability risks. Accurate information is needed for parents to make informed decisions about their baby's care. To determine if perinatal clinicians had accurate perceptions of outcomes of infants born at 23-25weeks' gestation, and if accuracy had changed over a decade. A web-based survey was sent to midwives, nurses, neonatologists, and obstetricians working in tertiary and non-tertiary hospitals, and the neonatal retrieval service in the state of Victoria in 2020. A similar survey had been completed in 2010. Clinicians' estimates of survival and major neurodevelopmental disability rates were compared with true rates for actively managed infants overall, and by infant birthplace and gestational age, and professional workplace and discipline. Accuracy of outcomes was compared between eras. Overall, 165 surveys were received. Participants underestimated survival (absolute mean difference [%] -14.4%; [95% confidence interval (CI) -16.6 to -12.3]; P<0.001) and overestimated major disability (absolute mean difference 32.7%; [95% CI 29.7 to 35.8]; P<0.001) rates overall, and at each week of gestation, and were worse for outborn compared with inborn infants. Perceptions of clinicians in tertiary centres were similar to those of non-tertiary clinicians. Nurses/midwives were more pessimistic, and paediatricians were more optimistic. Clinicians' perceptions of outcome were less accurate in 2020 than in 2010. Most perinatal clinicians underestimate survival and overestimate major disability of infants born at 23-25weeks' gestation, which may translate into overly pessimistic counselling of parents.

Effects of the Australian 2019–2020 megafires on a population of endangered broad‐headed snakes Hoplocephalus bungaroides

AbstractThe 2019–2020 Australian megafires were unprecedented in their intensity and extent. These wildfires may have caused high mortality of adult broad‐headed snakes Hoplocephalus bungaroides which shelter inside tree hollows during summer. We evaluated the impacts of two high‐intensity wildfires (2002 Touga Fire and 2020 Morton Fire) on a broad‐headed snake population in Morton National Park, south‐eastern Australia. We analysed a 29‐year mark–recapture data set to estimate survival rates of adults in years with and without wildfires, and with and without human disturbance to rock outcrops. To examine the short‐term effects of fire on occupancy, we analysed presence–absence data collected from 25 sites during 2019 and 2020. Estimates of occupancy were higher for 2020 (0.93 ± 0.09) than for 2019 (0.66 ± 0.14), while detection rates were constant (0.40 ± 0.06). Over the period 1992–2020, the best supported Cormack–Jolly–Seber model was one in which adult survival rates were high and stable (0.81 ± 0.04), but were 23% lower in years when humans disturbed rocks (0.63 ± 0.08). A model in which adult mortality was 20% higher in years with human disturbance and 14% higher in years with wildfires was also supported. Estimates of abundance revealed that the population declined by 34% after the Touga Fire, and 26% after the Morton Fire. Over the 29‐year study, the population has declined by 60%. Our results highlight how mortality events from wildfires need to be evaluated in the context of other threatening processes. For this population, the removal of snakes and associated habitat disturbance poses a more serious threat to population viability than infrequent wildfires.

Risk assessment tool implementation in congenital heart disease associated pulmonary arterial hypertension

Abstract Background Risk assessment is recommended for patients with congenital heart disease associated pulmonary arterial hypertension (CHD-PAH). Patients in intermediate or high risk may need intensified therapies to improve their survival. Purpose To compare an abbreviated version of the risk assessment strategy proposed by the current European PH guidelines, noninvasive French model, and an abridged version of the REVEAL 2.0 risk score calculator, REVEAL Lite 2. Methods We enrolled a mixed prevalent and incident cohort of patients with CHD-PAH from 6 PAH centers from January 2006 to December 2019 (n=126). Noninvasive French model comprising WHO functional class (FC), 6-minute walk distance (6 MWD), and N-terminal pro–brain natriuretic peptide (NT-pro BNP) or BNP was used. REVEAL Lite 2 includes FC, systolic blood pressure, heart rate, 6MWD, BNP/NT-pro BNP, and estimated glomerular filtration rate. Patients were grouped into three categories according to the number of non-invasive low-risk criteria (French model) and REVEAL Lite 2 scores. Risk was calculated based on the last available assessment at 12 months' follow-up, starting from enrollment. Kaplan-Meier (KM) survival was assessed in patients in each risk group with all-cause mortality as the end point. Log-rank test was used to compare estimates. Results The mean age was 32±16 years at diagnosis. The mean follow up was 99.41±58.2 months. 32 patients had died. Most patients were Eisenmenger Syndrome (39.4%) and simple defects (19.7%). Most patients had received monotherapy (74.5%). 66.6% of patients were WHO FC I–II, 29.3% III, and 3.9% IV (Table). Both models effectively discriminated risk in our cohort (p=0.0001). Patients achieving two or more noninvasive low-risk criteria or low risk category by REVEAL Lite 2 at follow-up had a significantly reduced risk of death. Figure demonstrates KM survival curves for noninvasive French model (A) and REVEAL Lite 2 (B). 51% of patients achieved 2 or more low risk criteria at follow-up. 56% of patients were in low risk at follow-up (REVEAL lite 2). The estimated survival rate at 5 years of patients meeting 2 and more low-risk criteria at follow-up was 100% vs. 86.8% for patients meeting 1 low-risk criterion and 59.6% for patients meeting 0 low-risk criterion. The corresponding survival rate was 65% for high-risk patient, 76.2% for intermediate-risk patient, and 100% for low-risk patient (REVEAL lite 2) (p=0.0001 by log-rank test; Figure). REVEAL Lite 2 approximates noninvasive French model at discriminating among patients at low, intermediate, or high risk based on c-index. Conclusions Both noninvasive French model and REVEAL Lite 2 provide a simplified and robust method of risk assessment for CHD-PAH. This analysis also supports the value of goal-oriented treatment in CHD-PAH. Patients who have less than 2 low-risk criteria or who have not achieved low risk category at follow-up may benefit from escalation of their treatment regimen. Funding Acknowledgement Type of funding sources: None.

Adaptive group sequential survival comparisons based on log-rank and pointwise test statistics.

Whereas the theory of confirmatory adaptive designs is well understood for uncensored data, implementation of adaptive designs in the context of survival trials remains challenging. Commonly used adaptive survival tests are based on the independent increments structure of the log-rank statistic. This implies some relevant limitations: On the one hand, essentially only the interim log-rank statistic may be used for design modifications (such as data-dependent sample size recalculation). Furthermore, the treatment arm allocation ratio in these classical methods is assumed to be constant throughout the trial period. Here, we propose an extension of the independent increments approach to adaptive survival tests that addresses some of these limitations. We present a confirmatory adaptive two-sample log-rank test that allows rejection regions and sample size recalculation rules to be based not only on the interim log-rank statistic, but also on point-wise survival rate estimates, simultaneously. In addition, the possibility is opened to adapt the treatment arm allocation ratio after each interim analysis in a data-dependent way. The ability to include point-wise survival rate estimators in the rejection region of a test for comparing survival curves might be attractive, e.g., for seamless phase II/III designs. Data-dependent adaptation of the allocation ratio could be helpful in multi-arm trials in order to successively steer recruitment into the study arms with the greatest chances of success. The methodology is motivated by the LOGGIC Europe Trial from pediatric oncology. Distributional properties are derived using martingale techniques in the large sample limit. Small sample properties are studied by simulation.

P-187: Expert elicitation of long-term survival (LTS) for patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with idecabtagene vicleucel (ide-cel, bb2121) in the KarMMa phase 2 trial

<h3>Background</h3> Cost-effectiveness analyses (CEA) of new treatments often need LTS extrapolations, but models can lack clinical expert evaluation. A systematic process can integrate expert opinion (EO) in an unbiased way. In the global multicenter, single-arm phase 2 KarMMa trial (NCT03361748), ide-cel, a B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cell therapy, showed deep, durable responses in triple-class exposed (TCE) pts with RRMM, with survival data reported up to 12 months (Munshi NC, et al. NEJM 2021;384:705-716). Without EO, predicted LTS varies with the extrapolation model. This study estimated expected survival rates at 3, 5, and 10 years for pts treated with ide-cel, based on integrating observed trial data with EO. <h3>Methods</h3> This prospective qualitative study incorporated semi-structured interviews, adapted from the Sheffield Elicitation Framework. Oncologists and hematologists with experience in treating pts with RRMM with BCMA-targeted therapies including CAR T cell therapies participated in the elicitation exercise (n=6). Evidence on pts in the KarMMa clinical trial from the Jan 2020 data cut (median follow-up 13.3 months) and conventional care (CC) for TCE pts with RRMM were summarized to give a common baseline data set for EO. In a facilitator-guided web-based application, experts gave upper and lower plausible limits and likely survival values at 3, 5, and 10 years. Experts were given the blinded, individual estimates and collectively gave consensus estimates from a ‘rationale impartial observer' perspective. To assess the impact of incorporating EO, separate models were based on observed data with or without EO. Exponential, Weibull, Gompertz, generalized gamma (GG), lognormal, and log-logistic survival distributions were used to assess model fit. Analyses used a Frequentist framework and the Akaike information criterion compared the goodness-of-fit in survival models. This process estimated LTS for CC from the observational studies KarMMa-RW (Jagannath S, et al. JCO 2020;38;8525) and MAMMOTH (Gandhi UH, et al. Leukemia 2019;33:2266-2275). <h3>Results</h3> The best-fitting distributions for models using observed ide-cel (KarMMa) data only vs observed data and EO were Gompertz and GG, respectively. Survival estimates were 11% (without EO) to 35% (with EO) at 3 years; 0% (without) to 15% (with) at 5 years; and 0% (without) to 2% (with) at 10 years. In comparison, for the real-world CC cohort in KarMMa-RW survival estimates (with EO) were 16%, 6%, and 1% at 3, 5, and 10 years, respectively, for the best-fitting (GG) model. For the MAMMOTH CC cohort, survival estimates (with EO) were 5%, 0%, and 0% at 3, 5, and 10 years for the best-fitting (GG) model. <h3>Conclusion</h3> These findings suggest when observed data and EO are integrated, ide-cel treatment provides extended estimated survival rates vs CC. This study indicates that including EO is informative in assisting decision-making processes.

Severely Atrophic Mandibles Restored With Fiber-Reinforced Composite Prostheses Supported by 5.0-mm Ultra-Short Implants Present High Survival Rates Up To Eight Years

Encouraging results have been reported for ultrashort single implants; however, long-term investigations are warranted for full-arch reconstructions. This study evaluated marginal bone loss, implant, and reconstruction survival of fiber-reinforced composite full-arch prostheses supported by 4 ultrashort implants. Patients with severely atrophic mandibles (Cawood and Howell class V and class VI) were included in this cohort study. Study predictors included time (initial and last follow-up) and vertical (epicrestally or subcrestally) and horizontal implant position (medial or lateral). Outcome variables included bone level changes over time, implant/prosthesis survival. Peri-implant bone level was measured on panoramic radiographs. Descriptive statistics, Kaplan-Meier, mixed model analysis of variance, and univariate and multivariate Cox Proportional Hazards Regression models, adjusted for multiple implants in the same patient, were used for data analyses. Eighteen patients (mean 61.22 years old), with 72 implants placed in atrophic mandibles with an average follow-up of 55.4 months (CI, ±4.6/ SD, ±10.6 months) were analyzed. The implant survival rate was 97.2% as 2 implants were not loaded due to non-osseointegration and sensorial disturbances. Average marginal bone level at baseline (1.93 mm) and at the time of last recall (1.91 mm) was not significantly different. While implants placed subcrestally showed no significant difference between baseline (1.91 mm) and last follow up bone level (2.12 mm), implants placed epicrestally demonstrated a significant reduction on their bone level over time (initial: 1.97 mm/ final:1.33 mm). Systemic disorders were a risk factor for implant survival and bone loss. Prostheses cumulative survival rate was 100% (mean observation period of 55 months). The estimated survival rate after the 96-month follow-up was 75% (1 framework fracture after 84 months). Fixed fiber-reinforced composite full-arch prostheses retained by 4 ultrashort implants showed a stable bone level and high implant/prostheses survival rates up to 8 years.

Association between emergency medical service transport time and survival in patients with traumatic cardiac arrest: a Nationwide retrospective observational study

BackgroundPatients with traumatic cardiac arrest (TCA) are known to have poor prognoses. In 2003, the joint committee of the National Association of EMS Physicians and the American College of Surgeons Committee on Trauma proposed stopping unsuccessful cardiopulmonary resuscitation (CPR) sustained for > 15 min after TCA. However, in 2013, a specific time-limit for terminating resuscitation was dropped, due to the lack of conclusive studies or data. We aimed to define the association between emergency medical services transport time and survival to demonstrate the survival curve of TCA.MethodsA retrospective review of the Japan Trauma Data Bank. Inclusion criteria were age ≥ 16, at least one trauma with Abbreviated Injury Scale score (AIS) ≥ 3, and CPR performed in a prehospital setting. Exclusion criteria were burn injury, AIS score of 6 in any region, and missing data. Estimated survival rate and risk ratio for survival were analyzed according to transport time for all patients. Analysis was also performed separately on patients with sustained TCA at arrival.ResultsOf 292,027 patients in the database, 5336 were included in the study with 4141 sustained TCA. Their median age was 53 years (interquartile range (IQR) 36–70), and 67.2% were male. Their median Injury Severity Score was 29 (IQR 22–41), and median transport time was 11 min (IQR 6–17). Overall survival after TCA was 4.5%; however, survival of patients with sustained TCA at arrival was only 1.2%. The estimated survival rate and risk ratio for sustained TCA rapidly decreased after 15 min of transport time, with estimated survival falling below 1%.ConclusionThe chances of survival for sustained TCA declined rapidly while the patient is transported with CPR support. Time should be one reasonable factor for considering termination of resuscitation in patients with sustained TCA, although clinical signs of life, and type and severity of trauma should be taken into account clinically.

Lake sturgeon (Acipenser fulvescens) annual adult survival estimated from acoustic telemetry

Survival of adult fishes is critical to the conservation and management of wild populations, particularly for long-lived, slow to reproduce species. Most sturgeon species are of conservation concern, but their long lifespans and large ranges have made estimation of adult survival rates challenging. In this study, acoustic telemetry was used to track 205 lake sturgeon (Acipenser fulvescens) tagged in the St. Clair and Detroit rivers of the Laurentian Great Lakes over seven years (2012–2019). The objective of this study was to determine if annual survival was related to sex, size, tagging location (river), or year post-tagging using Cormack-Jolly-Seber (CJS) models. Annual survival was high among all seven years (range of point estimates: 95–99%) and did not differ based on sex, tagging year, size at time of tagging, or tagging location. Lake sturgeon detection probability on acoustic receivers was high each year (range of point estimates: 82–99%) and increased as the number of receivers in the system increased. High survival rates of lake sturgeon were consistent with levels thought required for lake sturgeon to be self-sustaining in the St. Clair – Detroit river system. Our application of acoustic telemetry detections as input to CJS models demonstrated the usefulness of this approach and should be considered for population assessment studies throughout the Great Lakes and beyond.

LeopardPanthera pardusdensity and survival in an ecosystem with depressed abundance of prey and dominant competitors

AbstractThe leopardPanthera pardusis in range-wide decline, and many populations are highly threatened. Prey depletion is a major cause of global carnivore declines, but the response of leopard survival and density to this threat is unclear: by reducing the density of a dominant competitor (the lionPanthera leo) prey depletion could create both costs and benefits for subordinate competitors. We used capture–recapture models fitted to data from a 7-year camera-trap study in Kafue National Park, Zambia, to obtain baseline estimates of leopard population density and sex-specific apparent survival rates. Kafue is affected by prey depletion, and densities of large herbivores preferred by lions have declined more than the densities of smaller herbivores preferred by leopards. Lion density is consequently low. Estimates of leopard density were comparable to ecosystems with more intensive protection and favourable prey densities. However, our study site is located in an area with good ecological conditions and high levels of protection relative to other portions of the ecosystem, so extrapolating our estimates across the Park or into adjacent Game Management Areas would not be valid. Our results show that leopard density and survival within north-central Kafue remain good despite prey depletion, perhaps because (1) prey depletion has had weaker effects on preferred leopard prey compared to larger prey preferred by lions, and (2) the density of dominant competitors is consequently low. Our results show that the effects of prey depletion can be more complex than uniform decline of all large carnivore species, and warrant further investigation.

Behavior of Eosinophil Counts in Recovered and Deceased COVID-19 Patients over the Course of the Disease.

Knowledge about the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly regarding the function of eosinophils, has been steadily emerging recently. There exists controversy regarding the implications of eosinophils in the coronavirus disease 2019 (COVID-19)’s pathology. We report a retrospective cohort study including the comparison of leukocyte counts in COVID-19 patients, considering the outcomes of recovery (n = 59) and death (n = 60). Among the different types of leukocytes, the eosinophil counts were those that showed the greatest difference between recovered and deceased patients. Eosinopenia (eosinophil count < 0.01 × 109/L) was more frequently observed in deceased than recovered patients (p = 0.0012). The eosinophil counts more rapidly increased and showed a greater proportion over the course of the disease in the recovered than deceased patients. Furthermore, the estimated survival rate was greater in patients without eosinopenia than in patients with eosinopenia (p = 0.0070) during hospitalization. Importantly, recovered but not deceased patients showed high negative correlations of the eosinophils with the neutrophil-to-lymphocyte ratio (NLR) and neutrophil counts at Day 9 of the onset of clinical symptoms (p ≤ 0.0220). Our analysis suggests that eosinopenia may be associated with unfavorable disease outcomes and that the eosinophils have a beneficial function in COVID-19 patients, probably contributing by controlling the exacerbated inflammation induced by neutrophils.

Predictors of Lack of Relapse After Random Discontinuation of Oral and Long-acting Injectable Antipsychotics in Clinically Stabilized Patients with Schizophrenia: A Re-analysis of Individual Participant Data.

To quantify the risk and predictors of relapse among individuals with schizophrenia randomly withdrawn from antipsychotic maintenance treatment. We re-analyzed time-to-event and baseline predictors from placebo arms in five placebo-controlled randomized trials of antipsychotics (n = 688 individuals; 173 stabilized on oral antipsychotic [OAP] and 515 on long-acting injectables [LAI]) for relapse-prevention available in the Yale Open Data Access repository. Using a survival and Cox-proportional hazards regression analyses, we estimated survival rates of "relapse-free" individuals by the end of follow-up (median = 118 days, IQR = 52.0-208.0), the rate of study-confirmed relapse, and adjusted hazard ratios (aHR, 95% confidence intervals [CI]) associated with baseline predictors. We also estimated these parameters for individuals followed for >5 half-lives of the stabilizing antipsychotic, and studied predictors of "rebound psychosis" in OAP-stabilized participants, defined as occurring within 30 days of antipsychotic withdrawal. 29.9% (95%CI = 23.2-38.5) remained relapse-free by the end of follow-up, 11.1% (95%CI = 5.65-21.9) among those OAP-stabilized, 36.4% (95%CI = 28.4-46.7) among those LAI-stabilized. The study-confirmed relapse rate was 45.2%, 62.4% among those OAP-stabilized and 39.4% among those LAI-stabilized. Predictors of relapse included smoking (aHR = 1.54, 95%CI = 1.19-2.00), female sex (aHR = 1.37, 95%CI = 1.08-1.79), and having been stabilized on OAPs vs LAIs (aHR = 3.56, 95%CI = 2.68-4.72). Greater risk of relapse on OAP persisted even after sufficient time had elapsed to clear antipsychotic plasma level among LAI-stabilized (aHR = 5.0, 95%CI = 3.5-7.1). "Rebound psychosis" did not show predictors. Our results corroborate the high relapse risk following antipsychotic withdrawal after symptom stabilization with limited patient-related predictors of safe treatment discontinuation. Stabilization with LAIs reduces the short-/medium-term relapse risk.

Prevalence of fibrodysplasia ossificans progressiva (FOP) in the United States: estimate from three treatment centers and a patient organization

BackgroundFibrodysplasia ossificans progressiva (FOP), an ultra-rare, progressive, and permanently disabling disorder of extraskeletal ossification, is characterized by episodic and painful flare-ups and irreversible heterotopic ossification in muscles, tendons, and ligaments. Prevalence estimates have been hindered by the rarity of FOP and the heterogeneity of disease presentation. This study aimed to provide a baseline prevalence of FOP in the United States, based on contact with one of 3 leading treatment centers for FOP (University of Pennsylvania, Mayo Clinic, or University of California San Francisco), the International Fibrodysplasia Ossificans Progressiva Association (IFOPA) membership list, or the IFOPA FOP Registry through July 22, 2020.ResultsPatient records were reviewed, collected, and deduplicated using first and last name initials, sex, state, and year of birth. A Kaplan–Meier survival curve was applied to each individual patient to estimate the probability that he or she was still alive, and a probability-weighted net prevalence estimate was calculated. After deduplication, 373 unique patients were identified in the United States, 294 of whom who were not listed as deceased in any list. The average time since last contact for 284 patients was 1.5 years. Based on the application of the survival probability, it is estimated that 279 of these patients were alive on the prevalence date (22 July 2020). An adjusted prevalence of 0.88 per million US residents was calculated using either an average survival rate estimate of 98.4% or a conservative survival rate estimate of 92.3% (based on the Kaplan–Meier survival curve from a previous study) and the US Census 2020 estimate of 329,992,681 on prevalence day.ConclusionsThis study suggests that the prevalence of FOP is higher than the often-cited value of 0.5 per million. Even so, because inclusion in this study was contingent upon treatment by the authors, IFOPA membership with confirmed clinical diagnosis, and the FOP Registry, the prevalence of FOP in the US may be higher than that identified here. Thus, it is imperative that efforts be made to identify and provide expert care for patients with this ultra-rare, significantly debilitating disease.

Experience with cultured thymus tissue in 105 children

Currently, there are no approved therapies to treat congenital athymia, a condition of immune deficiency resulting in high early mortality due to infection and immune dysregulation. Multiple syndromic conditions, such as complete DiGeorge syndrome, 22q11.2 deletion syndrome, CHARGE (coloboma, heart defects, choanal atresia, growth or mental retardation, genital hypoplasia, and ear anomalies and/or deafness) syndrome, diabetic embryopathy, other genetic variants, and FOXN1 deficiency, are associated with congenital athymia. Our aims were to study 105 patients treated with cultured thymus tissue (CTT), and in this report, to focus on the outcomes of 95 patients with treatment-naive congenital athymia. A total of 10 prospective, single-arm open-label studies with patient enrollment from 1993 to 2020 form the basis of this data set. Patients were tested after administration of CTT for T-cell development; all adverse events and infections were recorded. A total of 105 patients were enrolled and received CTT (the full analysis set). Of those patients, 10 had diagnoses other than congenital athymia and/or received prior treatments. Of those 105 patients, 95 patients with treatment-naive congenital athymia were included in the efficacy analysis set (EAS). The Kaplan-Meier estimated survival rates at year 1 and year 2 after administration of CTT in the EAS were 77% (95% CI=0.670-0.844) and 76% (95% CI= 0.657-0.834), respectively. In all, 21 patients died in the first year before developing naive T cells and 1 died in the second year after receipt of CTT; 3 subsequent deaths were not related to immunodeficiency. Afew patients developed alopecia, autoimmune hepatitis, psoriasis, and psoriatic arthritis after year 1. The rates of infections, autologous graft-versus-host-disease manifestations, and autoimmune cytopenias all decreased approximately 1 year after administration of CTT. Treatment with CTT led to development of naive T cells with a 1-year survival rate of 77% and a median follow-up time of 7.6 years. Immune reconstitution sufficient to prevent infections and support survival typically develops 6 to12 months after administration of CTT.

Risk Stratification of Patients Undergoing Percutaneous Repair of Mitral and Tricuspid Valves Using a Multidimensional Geriatric Assessment.

Given their advanced age and high comorbidity, individual risk assessment is crucial in patients undergoing transcatheter mitral and tricuspid valve repair. Therefore, we evaluated the use of a comprehensive geriatric assessment score, the multidimensional prognostic index (MPI), for risk stratification in these patients. We conducted a prospective, observational single-center study, including 226 patients undergoing percutaneous repair for mitral or tricuspid regurgitation. The MPI was calculated preprocedural and covers 8 domains (activities of daily living, instrumental activities of daily living, mental status, nutrition, risk of pressure ulcers, comorbidity, medication, and marital/cohabitation status). We sought to identify an association of MPI score with procedural outcomes and 6-month mortality. A total of 53.1% of patients were stratified as low risk according to MPI (MPI-1 group), 44.2% as medium risk (MPI-2 group), and 2.7% as high risk (MPI-3 group). Procedural efficacy and safety were similar between groups. The estimated survival rate at 6 months was 97±2% in MPI-1 group, 79±4% in MPI-2 group (hazard ratio, 6.90 [95% CI, 2.36-12.2]; P≤0.001) and 50±20% in MPI-3 group (hazard ratio, 20.3 [95% CI, 4.51-91.3]; P<0.001). An increase in 1 SD of the MPI score (0.14 points, possible range of MPI score 0-1) was associated with a hazard ratio of 2.13 (95% CI, 1.58-2.73; P≤0.001) for death after 6 months. The risk association of the MPI with mortality remained significant in multivariate analysis including risk factors, such as peripheral artery disease and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. A comprehensive geriatric assessment with the MPI score provides additional information on mortality risk beyond established cardiovascular risk factors.