Estimate Survival Probabilities Research Articles

Oseltamivir Reduces 30-Day Mortality in Older Adults with Influenza: A Pooled Analysis from the 2012-2019 Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN)

Abstract Background Oseltamivir is recommended for the treatment of adults hospitalized with influenza, but adherence is often suboptimal. This may be due to doubts about the reliability of the evidence supporting its benefits, particularly when initiation is delayed. We aimed to assess the effectiveness of oseltamivir in reducing mortality in older adults hospitalized with influenza, with a focus on the timing of initiation. Methods The CIRN-SOS Network gathered data on severe respiratory illnesses across five Canadian provinces during the influenza seasons 2012-2019. Individuals aged 65+ years with confirmed influenza and available antiviral prescription data were included. We compared the 30-day survival rates of hospitalized patients based on oseltamivir prescription status. Kaplan-Meier estimated survival probability and IPT-weighted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for mortality. The analyses considered the time to antiviral initiation (>48 vs.≤48 h). Results Among the 8,135 influenza patients studied, 2,126 did not receive antiviral treatment, whereas 6,009 were treated with oseltamivir. A total of 395 patients were hospitalized for more than 30 days. The overall mortality rate was 8.32 per 1,000 person-days, with 53.9% of the deaths occurring within the first week. Oseltamivir recipients had a 18% lower risk of 30-day mortality (IPT-weighted HR=0.82, 95% CI: 0.69-0.98). The benefit was significant for influenza A (IPT-weighted HR=0.74, 95% CI: 0.61-0.91) but not for influenza B (IPT-weighted HR=1.12, 95% CI: 0.81-1.56). Oseltamivir remained effective even when initiated after 48 hours (IPT-weighted HR=0.66, 95% CI: 0.49-0.90). Influenza vaccination did not mediate the effectiveness of oseltamivir in reducing mortality. Conclusions Oseltamivir significantly reduces mortality risk in older adults hospitalized with influenza, even when administered after 48 h, independent of vaccination status.

Complication Rates Following Endoscopic Sinus Surgery for Chronic Sinusitis.

Endoscopic sinus surgery (ESS) is a minimally invasive procedure indicated for medically refractory chronic sinusitis (CRS). As with any surgical procedure, there are potential risks and complications. The purpose of this study is to report skull base, orbital, and hemorrhagic-associated complication rates following ESS. A retrospective query on the TriNetX platform identified patients diagnosed with CRS who subsequently underwent ESS in the last 20 years. Outcomes analyses were performed to determine the incidence of skull base (cerebrospinal fluid rhinorrhea, bacterial meningitis, dural tear), orbital (diplopia, optic nerve injury, blindness, epiphora, orbital hemorrhage, canthotomy/canthoplasty), and hemorrhagic (epistaxis, carotid artery injury, blood transfusion) complications within 30 days postoperatively. Kaplan-Meier Analysis estimated survival probability from each complication type. Outcome rates were also compared between female and male patients. A total of 116 669 patients from 55 healthcare organizations fit the study criteria. The average age at surgery was 47.9 ± 17.9 years. The gender distribution of the cohort was 50% female and 48% male. The risk of skull base, orbital, and hemorrhagic complications within 30 days of the surgery was found to be 0.212%, 0.741%, and 3.00%, respectively. Kaplan-Meier Analysis revealed that survival probability from each complication type was 99.783%, 99.260%, and 96.903%, respectively. Comparison of outcome risks stratified by gender revealed no major differences for skull base and orbital complications; however, males exhibited a significantly higher risk of hemorrhagic complications (3.2% vs 2.8%, P < .0001). The study supports ESS as a safe procedure for the management of CRS. Though rare, hemorrhagic complications are more common than orbital and skull base complications. Hemorrhagic complications are also more common in men than women. These findings provide insights for counseling patients about ESS risks and benefits.

Neurobrucellosis: a retrospective cohort of 106 patients

BackgroundNeurobrucellosis, a serious central nervous system infection caused by Brucella species, presents significant challenges due to its diverse clinical manifestations and the risk of long-term complications and poor outcomes. Identifying predictors of adverse outcomes is critical for improving patient management and overall prognosis.ObjectivesThis study aimed to evaluate the long-term morbidity and mortality associated with neurobrucellosis and to identify key predictors of adverse outcomes.MethodsWe performed a retrospective cohort study of 106 neurobrucellosis patients treated at two major referral centers in Mashhad, Iran, from March 21, 2011, to March 20, 2022. We analyzed clinical, neuroimaging, and laboratory data, and estimated survival probabilities using Kaplan–Meier analysis. Long-term morbidity was evaluated using the Glasgow Outcome Scale.ResultsThe median age of the cohort was 30 years (IQR: 21.8–46.3). The median length of hospital stay was 11 days (IQR: 7–19.8), with an in-hospital mortality rate of 4.7% (n = 5). Survival probabilities were 92.2% (SE = 0.027) at 1 month and 90.1% (SE = 0.030) at 6 months. The median follow-up duration was 52 months (IQR: 35–77). At follow-up, 23.5% (n = 20) of patients had an unfavorable outcome based on the Glasgow Outcome Scale. Predictors of mortality included older age, altered level of consciousness, seizures, elevated body temperature on admission, and white matter changes on neuroimaging.ConclusionNeurobrucellosis is associated with significant long-term morbidity and mortality. Key predictors of mortality include older age, altered level of consciousness, seizures, elevated body temperature on admission, and white matter changes. Identifying these predictors can help in targeting therapeutic strategies and improving patient outcomes through early intervention and close monitoring.

The value of a metabolic and immune-related gene signature and adjuvant therapeutic response in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a dismal prognosis. Treatment outcomes exhibit substantial variability across patients, underscoring the urgent need for robust predictive models to effectively estimate survival probabilities and therapeutic responses in PDAC. Metabolic and immune-related genes exhibiting differential expression were identified using the TCGA-PDAC and GTEx datasets. A genetic prognostic model was developed via univariable Cox regression analysis on a training cohort. Predictive accuracy was assessed using Kaplan-Meier (K-M) curves, calibration plots, and ROC curves. Additional analyses, including GSAE and immune cell infiltration studies, were conducted to explore relevant biological mechanisms and predict therapeutic efficacy. An 8-gene prognostic model (AK2, CXCL11, TYK2, ANGPT4, IL20RA, MET, ENPP6, and CA12) was established. Three genes (AK2, ENPP6, and CA12) were associated with metabolism, while the others were immune-related. Most genes correlated with poor prognosis. Validation in TCGA-PDAC and GSE57495 datasets demonstrated robust performance, with AUC values for 1-, 3-, and 5-year OS exceeding 0.7. The model also effectively predicted responses to adjuvant therapy. This 8-gene signature enhances prognostic accuracy and therapeutic decision-making in PDAC, offering valuable insights for clinical applications and personalized treatment strategies.

The APP Score: A simple serum biomarker model to enhance prognostic prediction in hepatocellular carcinoma

The prognosis for patients with hepatocellular carcinoma (HCC) depends on tumor stage and remnant liver function. However, it often includes tumor morphology, which is usually assessed with imaging studies or pathologic analysis, leading to limited predictive performance. Therefore, the aim of this study was to develop a simple and low-cost prognostic score for HCC based on serum biomarkers in routine clinical practice. A total of 3,100 patients were recruited. The least absolute shrinkage and selector operation (LASSO) algorithm was used to select the significant factors for overall survival. The prognostic score was devised based on multivariate Cox regression of the training cohort. Model performance was assessed by discrimination and calibration. Albumin (ALB), alkaline phosphatase (ALP), and alpha-fetoprotein (AFP) were selected by the LASSO algorithm. The three variables were incorporated into multivariate Cox regression to create the risk score (APP score = 0.390* ln (ALP) + 0.063* ln(AFP) - 0.033*ALB). The C-index, K-index, and time-dependent AUC of the score displayed significantly better predictive performance than 5 other models and 5 other staging systems. The model was able to stratify patients into three different risk groups. In conclusion, the APP score was developed to estimate survival probability and was used to stratify three strata with significantly different outcomes, outperforming other models in training and validation cohorts as well as different subgroups. This simple and low-cost model could help guide individualized follow-up.

Implementation of the advanced HIV disease package of care using a public health approach: lessons from Nigeria

BackgroundNigeria adapted the WHO package of care for Advanced HIV Disease (AHD) in 2020. The package includes CD4 + cell count testing to identify People Living with HIV (PLHIV) with AHD, screening and treatment of opportunistic infections, rapid antiretrovirals (ART) initiation, and intensive adherence follow-up. The national program adopted a phased approach in the rollout of the AHD package of care to learn lessons from a few representative health facilities before scaling up across the country. This study describes the process and lessons learned from the first phase of implementation.MethodsThis was a prospective observational study, and participants were enrolled between February and September 2021. Healthcare-worker (HCW) capacity was built to implement the AHD package of care. The study population included newly diagnosed PLHIV ≥ 10 years presenting to care in 28 selected facilities across 4 states in Nigeria. Eligible participants received CD4 + cell testing at baseline. Those with CD4 + cell count < 200 cells/mm3 were subjected to a blood cryptococcal antigen (CrAg) test and urine TB lateral flow lipoarabinomannan (LF-LAM). Those with positive CrAg tests had a cerebrospinal fluid (CSF) test to confirm cryptococcal meningitis. Those negative for both blood CrAg and TB LF-LAM were rapidly initiated on ART and underwent intensive follow-up. Participants were followed up for 12 months.ResultsA total of 6,781 patients were enrolled; 71% (4,812) received CD4 + cell count test, of which 41% (1,969 of 4812) had a CD4 + count < 200 cells/mm3. Approximately 81% (1,492 of 1,850) of those with CD4 + count < 200 cells/mm3 had TB LF-LAM test results documented; 25% were positive, of which 47% started TB treatment. Blood CrAg screening coverage among those with CD4 + count < 200 cells/mm3 was 88% (1,634 of 1,850), of which 5% (85 of 1,634) were positive. Cotrimoxazole preventive therapy was initiated for 65% (1,198 of 1,850) of the participants with CD4 + count < 200 cells/mm3, and 70% (966 of 1,375) of AHD patients with a negative TB LF-LAM and blood CrAg results were initiated on ART on the day of enrolment. Approximately 91% (421 of 461) of those who received viral load results at month 12 post-enrollment were virally suppressed. The retention rate and the Kaplan Meier survival probability estimate at month 12 were 65% (1,204 of 1,850) and 0.93 (CI, 0.91–0.94), respectively, for the enrolled participants.ConclusionImplementation of the AHD package of care in Nigeria has improved the diagnosis of TB and CM, and will potentially enhance the quality of care for PLHIV if sustained. Findings from this implementation were used to guide national scale-up.

Factors affecting the length of productive life in U.S. Katahdin ewes.

The length of ewe productive life (LPL), defined as the number of days between the first and last lambing, is a key indicator of ewe longevity and is directly related to the sustainability of the sheep industry. Therefore, the primary objective of this study was to investigate systematic effects influencing LPL in Katahdin sheep. The LPL of 10,474 Katahdin ewes (69.5% with uncensored and 30.5% with right-censored observations) born between 1992 and 2021 in 58 flocks located across the United States were analyzed. The Kaplan-Meier (K-M) and Cox Proportional Hazard (Cox PH) methods were used to estimate survival probability. Four Cox PH models were evaluated. Model 1 included contemporary group (CG; flock-year-season of ewe birth) as a random effect and the ewe's dam's age (EDA), ewe's own birth-rearing type (BR; 1/1, 2/1, 2/2, 3/2, 3/3, with the digit-3 including lamb counts ≥3), and age at first lambing (AFL) as fixed effects. Models 2 to 4 were an extension of model 1. Model 2 also included average lamb birth weight (ABW) per ewe lifetime, while model 3 included average lamb weaning weight (AWW) per ewe lifetime. Both ABW and AWW were fitted as fixed effects. Model 4 fitted all previous effects together. The factors CG, BR, ABW, and AWW affected LPL (P < 0.05) in all models in which these effects were fitted. The EDA effect only influenced LPL (P < 0.05) in model 1, while AFL had no effect (P > 0.05) in any model. The median LPL ranged from approximately 2 to 3 yr, depending on the risk factors analyzed. In general, Katahdin ewes themselves born in multiple litters, and that produced lambs weighing ~5kg at lambing and 20 to 25kg at weaning (over their lifespan) had better survival probability. Although the LPL of Katahdin sheep is relatively low, it appears to be a consequence of voluntary culling due to its association with both ABW and AWW. Future studies should quantify the rate of involuntary culling in Katahdin ewes to identify whether longevity indicator traits should be included in more comprehensive breeding objectives.

Aetiology, Treatment and Outcomes of Pericarditis: Long-Term Data from a Longitudinal Retrospective Single-Centre Cohort.

Background. Pericarditis has a heterogeneous clinical spectrum and rate of relapse. Data on aetiology, real-life treatment strategies, and long-term course from contemporary pericarditis cohorts are lacking. Methods. Pericarditis patients referred to the Cardioimmunology Outpatient Clinic at Padua University Hospital in 2001-2020 were retrospectively included. Kaplan-Meier method was used for recurrence-free survival probability estimation. The appropriateness of treatment was assessed based on the European Society of Cardiology guidelines. Results. One-hundred forty-four patients (57% males, mean age 50 years) followed up for 18 months (IQR 7-45) were included; of those, 52% had acute, 35% recurrent, 8% incessant, and 5% chronic pericarditis; 9% had cardiac tamponade at diagnosis. Time to pericardial effusion resolution was 53 days (IQR 16-124); median medical treatment duration was 87 days (IQR 48-148). Treatment was readjusted following the ESC guidelines for nonsteroidal anti-inflammatory drugs in 29% of the cases, steroids in 12%, and colchicine in 25%. Eleven (8%) patients were treated with anti-IL1 agents. Recurrence-free survival probability was 86% at 1st-year follow-up, and 23 patients (16%) had at least one recurrence, with a mean of two relapses per patient. Compared to patients without recurrences, they had a higher frequency of cardiac tamponade (27% vs. 6%, p = 0.006) and left bundle branch block (14% vs. 1%, p = 0.034). Out of the 144 patients, 5 (3%) were diagnosed as having constrictive pericarditis at first evaluation at our clinic, underwent successful pericardiectomy, and are currently alive and asymptomatic. Conclusions. When treated following a guideline-based approach, pericarditis has a favourable evolution. A relevant quote of cases benefits from the treatment readjustment of previously prescribed medical therapy when not in line with ESC recommendations. Cases relapsing despite treatment readjustment should receive anti-IL1 therapies.

Transcatheter Aortic Valve Replacement in Patients With Geographic and Socioeconomic Vulnerabilities.

Transcatheter aortic valve replacement (TAVR) is an established treatment for patients with severe aortic stenosis (AS). It remains unclear whether disparities exist in rural or socially vulnerable populations undergoing TAVR. This study assessed whether outcomes differ based on geographic location or vulnerability of patients undergoing TAVR. Patients undergoing TAVR at a single institution from August 2012 to June 2023 were studied (n = 1565). Zip codes determined Social Vulnerability Index (SVI) and measured distance to our facility. Outcomes defined by the Valve Academic Research Consortium 3 (VARC-3) included stroke, transient ischemic attack (TIA)/delirium, pacemaker implantation, new atrial fibrillation/atrial flutter, and myocardial infarction (MI). Average time between preoperative coronary angiogram (CATH)/computed tomography angiography (CTA) and TAVR was calculated. Kaplan-Meier curves estimated survival probability. The average time between CATH and TAVR in patients living furthest away was ∼9 days more than patients living closest to the implant site. The average number of days between CATH and TAVR for low and high SVI were 71 and 78 days, respectively. The average number of days between CTA and TAVR for low and high SVI were 40 and 39 days, respectively. Further distances traveled were associated with longer wait times between preoperative workup and TAVR. Patients with longer waits between CATH and TAVR had no differences in medium-term survival probability but had decreased long-term survival probability compared to patients with rapid pre-procedural evaluation. Although geographic and socioeconomic vulnerability can disadvantage patients, our study demonstrates that patients undergoing TAVR can have timely care and similar outcomes.

NCMP-07. ADVERSE NEUROLOGIC COMPLICATIONS FOLLOWING IMMUNE CHECKPOINT INHIBITORS FOR TREATMENT OF MELANOMA: COMPARATIVE ANALYSIS OF PD-1 INHIBITOR MONOTHERAPY TO COMBINATION THERAPY WITH CTLA-4 INHIBITORS

Abstract In the past decade, FDA approval of several novel immune checkpoint inhibitors (ICI) has revolutionized treatment of advanced melanoma. However, severe immune-related adverse events (irAEs) from these medications have been reported. This study examines whether PD-1/CTLA-4 inhibitor combination immunotherapy confers increased incidence of neurologic irAEs in melanoma patients compared to PD-1 inhibitor monotherapy. A retrospective, multicenter cohort study performed using TriNetX research platform identified adult patients diagnosed with melanoma. Cohort 1 (n=9,105) included melanoma patients treated with PD-1 inhibitor monotherapy (pembrolizumab or nivolumab). Cohort 2 (n=4,727) included melanoma patients treated with PD-1/CTLA-4 inhibitor combination therapy (PD-1 inhibitor + ipilimumab). Propensity Score Matching generated final cohorts (n=4,667) using covariates: gender, race, age at diagnosis, and history of nervous system disorders. Odds ratios (OR) were determined for the occurrence of neurologic irAEs at 3 years and 5 years following therapy initiation. Kaplan Meier analysis estimated survival probabilities for each irAE subtype, as defined by the 2021 Neuro irAE Disease Definition Panel. At 3 years post-diagnosis, there was increased risk of meningitis [OR: 2.8, 95% CI: (1.8, 4.2)], encephalitis [OR: 3.1, 95% CI: (1.9, 5.1)], demyelinating syndromes [OR: 2.7, 95% CI: (1.4, 5.2)], vasculitis [OR: 1.2, 95% CI: (0.5, 2.8)], peripheral neuropathy [OR: 1.3, 95% CI (1.1, 1.5)], neuromuscular junction disorders [OR: 1.1, 95% CI: (0.7, 1.8)], and myopathy [OR: 1.4, 95% CI: (1.1, 1.9)] in melanoma patients receiving combination immunotherapy compared to those receiving anti-PD-1 monotherapy. Increased incidence of neurologic irAEs corresponded with marginally lower, yet statistically significant decreases in survival probability (p&amp;lt;0.01), except for vasculitis (p=0.2) and neuromuscular junction irAEs (p=0.3). At 5 years following therapy initiation, these trends persisted. Melanoma patients receiving anti-PD-1/CTLA-4 combination therapies are at greater risk of neurologic irAEs than patients on anti-PD-1 monotherapy. Incidence of neurologic irAEs may confer worsened survival prognosis for these patients.

Forecasting age distribution of life-table death counts via α-transformation

We introduce a compositional power transformation, known as an α-transformation, to model and forecast a time series of life-table death counts, possibly with zero counts observed at older ages. As a generalisation of the isometric log-ratio transformation (i.e. α = 0 ), the α transformation relies on the tuning parameter α, which can be determined in a data-driven manner. Using the Australian age-specific period life-table death counts from 1921 to 2020, the α transformation can produce more accurate short-term point and interval forecasts than the log-ratio transformation. The improved forecast accuracy of life-table death counts is of great importance to demographers and government planners for estimating survival probabilities and life expectancy and actuaries for determining annuity prices and reserves for various initial ages and maturity terms.

The Effectiveness of NP001 on the Long-Term Survival of Patients with Amyotrophic Lateral Sclerosis.

The aim of this study was to estimate the effect of a 6 months' treatment course of the innate immune modulator NP001 (a pH-adjusted intravenous formulation of purified sodium chlorite), on disease progression, as measured by overall survival (OS) in patients with amyotrophic lateral sclerosis. Blinded survival data were retrospectively collected for 268 of the 273 patients who had participated in two phase 2 placebo-controlled clinical trials of NP001 (ClinicalTrials.gov: NCT01281631 and NCT02794857) and received at least one dose of either 1 mg/kg or 2 mg/kg of NP001 as chlorite based on actual body weight, or placebo. Kaplan-Meier methods were used on the intent-to-treat population to estimate survival probabilities. In the overall population, the median OS was 4.8 months (2.7 years [95% CI: 2.3, 3.5] in the 2 mg/kg NP001group and 2.3 years [95% CI: 1.8, 2.9] in the placebo group). Hazard ratio (HR): 0.77 (95% CI: 0.57, 1.03), p = 0.073. Among patients aged ≤ 65 years, the median OS for the 2 mg/kg NP001 group was 10.8 months (3.3 years [95% CI: 2.4, 3.8] in the 2 mg/kg NP001 group and 2.4 years [95% CI: 1.7, 3.3] in the placebo group). HR: 0.69 (95% CI: 0.50, 0.95). No differences were observed in the 1 mg/kg NP001 group or in patients aged > 65 years. The findings from this study suggest that a 6 months' treatment course of NP001 resulted in a 4.8-month increase in overall survival in patients with ALS. The findings from this study indicate that targeting inflammation associated with the innate immune system may provide a pathway for new therapeutic options for the treatment of ALS.

Population dynamics of a desert riverine turtle, Pseudemys gorzugi, at the northern edge of its range

Estimating the key demographic parameters of animal populations can enhance our understanding of system dynamics and assist in developing and improving conservation decision–support models. The Rio Grande cooter Pseudemys gorzugi is a conservation reliant freshwater turtle native to lower Rio Grande River Basin (USA and Mexico), with limited knowledge regarding its natural history and population dynamics. In this study, we used seven years of capture–mark–recapture data from the northern edge of the species' range to estimate survival probabilities, changes in abundance, and the probability of transitioning between different size classes while explicitly accounting for the sampling process. We found relatively high survival probabilities across different strata, with large juveniles exhibiting the highest survival (0.98) and small juveniles the lowest (0.71). However, transition probabilities between strata were low, indicating slow somatic growth rates. Our pattern‐oriented modelling revealed a low overall mean estimate of egg survival (0.024), warranting further empirical confirmation. Our study provides the first comprehensive demographic analysis of P. gorzugi encompassing an array of size and sex classes. Overall, we consider the population of P. gorzugi in the Black River robust, highlighting the importance of this river system to the species' persistence in the northern extent of its range, where the population is isolated from its broader distribution. The demographic estimates and ecological insights provided by our study offer critical data for parameterizing decision‐support models to ensure that P. gorzugi conservation strategies are grounded in the best available science.

Outcomes with initiation of inpatient immunotherapy.

7 Background: Immune checkpoint inhibitors (ICIs) have transformed cancer care; however, studies establishing their benefit have been primarily conducted in robust patients (pts) with good performance status. Administration of ICI to hospitalized pts remains a subject of debate. While there is often a desire to reverse clinical course in patients who are acutely ill, previous studies show minimal benefit from anticancer therapy near the end of life with the potential for toxicity. While ICI are generally better tolerated than traditional cancer therapies, the median time to response ranges from 2-6 months and pts with a poor PS may not derive benefit. ICIs also bring significant financial burdens to pts and healthcare systems. The role of ICIs in the inpatient setting remains unclear. Methods: This study retrospectively examined pts who received PD-(L)1 inhibitors while IP between 2016 and 2023 at MedStar Georgetown University Hospital. Data were collected manually from institutional EMR. Descriptive statistics were used to depict the pt population and show their outcomes. The Kaplan-Meier method estimated survival probabilities from treatment initiation to follow-up or death, with 95% confidence intervals (α = 0.05). The Log rank non-parametric test compared survival distributions among ICIs. Results: Of the 38 pts who initiated ICI as an inpatient, 16 were male (42.1%) and 22 were female (57.9%). The median age was 60 years (31–88 years). Gastrointestinal malignancies were most common indication (31.6%), followed by thoracic/head and neck (21.1%) and hematologic (18.4%) cancers. Among the cohort, 26.3% received nivolumab, 68.4% received pembrolizumab, and 5.3% received a combination of nivolumab and ipilimumab. PD-L1 status was unknown for the majority (79.0%) of pts at time of ICI; 15.8 % were known to be PD-L1 high. Only 14 of 35 (40.0%) patients went on to receive any additional immunotherapy after discharge. The median days to death after discharge was 16 days (0-376 days), with a mean of 36.4 days. The median overall survival was 137 days from IP treatment initiation. The survival probability at 91 days was 65.5% (95% CI: 45.4-79.7) and 31.0% (95% CI: 15.6-47.9) at 182 days. No significant differences were observed between the survival distributions by ICI type (p=0.966) or primary malignancy (p=0.488). Conclusions: Our findings underscore the complexities of initiating inpatient ICI treatment and question its appropriateness. Delaying ICI to outpatient settings may enhance pt tolerance, optimize outcomes, and potentially mitigate unnecessary costs. This approach may allow thorough consideration of performance status outside the hospital, possibly improving treatment effectiveness while reducing futile acute care costs.

Clinical features and prognostic factors of patients with inoperable hepatocellular carcinoma treated with chemotherapy: a population-based study.

In inoperable hepatocellular carcinoma (HCC), chemotherapy is a common treatment strategy. However, there is a lack of reliable methods to predict the prognosis of patients with inoperable HCC after chemotherapy. Therefore, the aim of this study was to identify the clinical characteristics of patients with inoperable HCC and to establish and validate nomogram models for predicting the survival outcomes in this patient group following chemotherapy. The data of patients diagnosed with HCC from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Logistic regression analyses were used to identify potential factors for inoperability in patients with HCC. Kaplan-Meier analyses were applied to evaluate the impact of chemotherapy on prognosis. Additionally, Cox regression analyses were performed to identify the potential risk factors associated with overall survival (OS) and cancer-specific survival (CSS) in patients with inoperable HCC treated with chemotherapy. Finally, we constructed prognostic nomograms for predicting the 1- and 3-year survival probabilities. A total of 3,519 operable patients with HCC and 4,656 patients with inoperable HCC were ultimately included in this study. Logistic regression analyses revealed a significant association between patient age, gender, race, tumor, node, metastasis (TNM) stage, tumor size, pretreatment alpha fetoprotein (AFP) levels, and marital status with inoperability. Moreover, Kaplan-Meier analyses revealed a significant improvement in both OS and CSS with the administration of chemotherapy. Moreover, 1,456 patients with inoperable HCC were enrolled in the training group and 631 patients with inoperable HCC were enrolled in the validation group to develop and validate the prognostic models. Cox regression models indicated that TNM stage, tumor size, and pretreatment AFP were independent risk factors for predicting OS and CSS in patients with inoperable HCC receiving chemotherapy. These factors were subsequently integrated into the predictive nomograms. We preliminarily developed survival models with strong predictive capabilities for estimating survival probabilities in patients with HCC following chemotherapy. These models hold potential for clinical application and warrant further exploration through additional studies.

Survival analysis of diabetes mellitus and cardiovascular patients with COVID-19: a secondary data analysis

Background: Patients with diabetes mellitus (DM) and cardiovascular disorders who suffer from COVID-19 may have an increased risk of death. Objective: This study aims to analyze the time of death and influencing factors in patients with DM and cardiovascular disorders with COVID-19. Methods: We used a retrospective observational cohort study using medical records of COVID-19 patients treated at Dr Soeradji and Penembahan Senopati hospitals from March 2020 to June 2022. There were 2,959 participants: patients without comorbidities, with DM, and with cardiovascular problems. We extracted sociodemographic and clinical data on patient characteristics using medical records. Data analysis used Kaplan-Meier and Cox regression analysis to estimate survival probability and investigate predictors of death with a 5% significance level. Results: The median survival time was highest in the group without comorbidities (70.00) and lowest in the DM+others group (21.75). Years of treatment, age, presence of comorbidities, and type of hospital were related to the survival rate of COVID-19 patients (p&lt;0.05). Diabetes mellitus and cardiovascular system disorders are significantly associated with survival of COVID-19 patients (p&lt;0.001). There were significant differences between patients without cardiovascular disorders and patients with cardiovascular disorders (Non-Hypertension, Hypertension, and Hypertension + Others) adjusted by year, gender, age, and hospital type (p&lt;0.001). There were significant differences between patients without DM and patients with DM (DM only, DM+Hypertension, and DM+Others) adjusted by year, gender, age, and hospital type(p&lt;0.001). Conclusion: Years of treatment, age, gender, comorbid DM, and cardiovascular problems are associated with the survival rate of COVID-19 patients. Older age, DM patients who have comorbidities other than hypertension, and patients with cardiovascular issues other than hypertension show a greater risk of death than other groups. Key words: COVID-19, Diabetes Mellitus, Hypertension, Cardiovascular Diseases, Survival Rate.

Real Clinical Practice of Combined Atezolizumab Plus Chemotherapy in Patients With Small Cell Lung Cancer.

Atezolizumab, an anti-PD-L1 antibody, has been increasingly administered in combination with chemotherapy to patients with small cell lung cancer (SCLC). This study aimed to determine how patients with extensive disease (ED) -SCLC responded to atezolizumab with chemotherapy and found factors affecting long-term response and survival. This study focused on patients with SCLC who were treated with a combination of atezolizumab and chemotherapy in Japan between 2019 and 2023. Patient information and tumor response were analyzed, along with adverse events. We compared data and estimated survival probabilities. In our clinical trial, 95 patients with SCLC who received this treatment had a median progression-free survival of 6.0 months and a median overall survival of 15.0 months. Immune-related adverse events were observed in 13.7% of the patients, with grade 3 or higher in 5.3%. The efficacy and immune-related adverse events associated with this treatment regimen were comparable to those reported in previous clinical trials. Progression-free survival >2 years was observed in a small number of patients (5.3%). Our research will offer important insights for the future care of patients with extensive-stage SCLC by utilizing atezolizumab in combination with chemotherapy. Accumulation and confirmation of clinical practice results will have important implications for the future implementation of this therapy.

Overall survival in patients with acute lymphoblastic leukemia treated with protocol CALGB 9511 at a tertiary hospital in the state of Ceará.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common neoplasm in childhood and has high survival rates. In adults, due to the biological characteristics of the disease and chemotherapy-related toxicity, survival is lower. CALGB 9511 is a chemotherapy protocol based on pediatric regimens with high remission rates after induction. Objectives: To evaluate the survival of patients with ALL undergoing the CALGB 9511 protocol at Walter Cantídio University Hospital (HUWC); to describe the impact of risk factors: presence of measurable residual disease, BCR-ABL fusion gene status, and allogeneic bone marrow transplant (BMT) on the survival of this group. Methodology: Retrospective evaluation of medical records of patients with ALL treated with this protocol between 2011 and 2022. Statistical analysis was performed using the Kaplan-Meier method to estimate survival probability. Results: 79 patients were eligible; 19% were BCR-ABL positive; the mean 2-year overall survival was 44%; The 2-year survival rate for patients undergoing HSCT was approximately 78%.. Conclusion: The survival curves of the study conducted at HUWC are similar to those described in the literature and corroborate the severity of the disease. Accessibility to new therapeutic modalities is a strategy that can improve the survival of these patients.

FLT3-MUTATED ACUTE MYELOID LEUKEMIA OUTCOMES IN A NORTHEAST BRAZILIAN UNIVERSITY HOSPITAL

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene occur in approximately 25-45% of new diagnoses of Acute myeloid leukemia. The addition of FLT3 inhibitors to conventional protocols improves overall survival in this condition. Objectives: To assess the incidence of FLT3 gene mutation among patients diagnosed with AML at Walter Cantídio University Hospital; Describe access to FLT3 inhibitors and bone marrow transplantation (BMT), and the overall survival of this group. Methodology: Retrospective evaluation of medical records of patients treated for AML between 2020 and 2022. Statistical analysis was performed using the Kaplan-Meier method to estimate survival probability. Results: 47 patients were diagnosed with AML during this period, of whom 17% had FLT3+ mutation. 3/8 patients accessed FLT3 inhibitors. The median survival with FLT3+ mutation was 9.1 months vs. 12.9 months in FLT3- (p = 0.196). The overall survival of AML patients was 30.9% at 2 years. 11/47 patients underwent allogeneic BMT. Conclusion: The addition of targeted therapies and BMT may contribute to reduce mortality in AML. Elderly patients and those not undergoing HSCT have worse outcomes.

RRP8, associated with immune infiltration, is a prospective therapeutic target in hepatocellular carcinoma

BackgroundRibosomal RNA Processing 8 (RRP8) is a nucleolar Rossman fold-like methyltransferase that exhibits increased expression in many malignant tumours. However, the role of RRP8 in hepatocellular carcinoma (HCC) is still uncertain. We explored the relationships between RRP8 and prognosis and immune infiltration, as well as the putative pathological function and mechanism of RRP8 in HCC.MethodsAnalysis of RRP8 expression across cancers was performed by using multiple databases. Associations between RRP8 expression and clinicopathological factors were further examined. Gene enrichment analysis was used to identify various putative biological activities and regulatory networks of RRP8 in HCC. The relationship between RRP8 expression and immune infiltration was confirmed by single-sample gene set enrichment analysis (ssGSEA). Univariate and multivariate Cox regression analyses were conducted to assess the impact of clinical variables on patient outcomes. Furthermore, a nomogram was constructed to estimate survival probability based on multivariate Cox regression analysis. Functional validation of RRP8 in HCC was performed with two different systems: doxycycline-inducible shRNA knockdown and CRISPR-Cas9 knockout.ResultsRRP8 was markedly overexpressed in HCC clinical specimens compared to adjacent normal tissues. Further analysis demonstrated that RRP8 was directly connected to multiple clinical characteristics and strongly associated with various immune markers in HCC. Moreover, elevated RRP8 expression indicated an unfavourable prognosis. Our functional studies revealed that both knockdown and knockout of RRP8 dramatically attenuated liver cancer cells to proliferate and migrate. Knockout of RRP8 decreased the phosphorylation of MEK1/2 and β-catenin-(Y654) signalling pathway components; downregulated downstream signalling effectors, including Cyclin D1 and N-cadherin; and upregulated E-cadherin.ConclusionsRRP8 is strongly implicated in immune infiltration and could be a potential therapeutic target in HCC.