Risk Factors For Early Progression Research Articles

[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial

Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

Risk Factor Analysis and Nomogram for Early Progression of COVID-19 Pneumonia in Older Adult Patients in the Omicron Era.

Timely recognition of risk factors for early progression in older adult patients with COVID-19 is of great significance to the following clinical management. This study aims to analyze the risk factors and create a nomogram for early progression in older adult patients with COVID-19 in the Omicron era. A total of 272 older adults infected with COVID-19 admitted from December 2022 to February 2023 were retrospectively recruited. Risk factor selection was determined using the logistic and the least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then created to predict early progression, followed by the internal validation and assessment of its performance through plotting the receiver operating characteristic (ROC), calibration, and decision curves. A total of 83 (30.5%) older adult patients presented an early progression on chest CT after 3-5 days of admission under standard initiate therapy. Six independent predictive factors were incorporated into the nomogram to predict the early progression, including CRP > 10 mg/L, IL-6 > 6.6 pg/mL, LDH > 245 U/L, CD4+ T-lymphocyte count <400/µL, the Activities of Daily Living (ADL) score ≤40 points, and the Mini Nutritional Assessment Scale-Short Form (MNA-SF) score ≤7 points. The area under the curve (AUC) of the nomogram in discriminating older adult patients who had risk factors in the training and validation cohort was 0.857 (95% CI 0.798, 0.916) and 0.774 (95% CI 0.667, 0.881), respectively. The calibration and decision curves demonstrated a high agreement in the predicted and observed risks, and the acceptable net benefit in predicting the early progression, respectively. We created a nomogram incorporating highly available laboratory data and the Comprehensive Geriatric Assessment (CGA) findings that effectively predict early-stage progression in older adult patients with COVID-19 in the Omicron era.

Outcomes of BCMA-Directed Chimeric Antigen Receptor T-Cell (CART) Therapy in Patients with Relapse-Refractory Multiple Myeloma with Extramedullary Disease

Background: Presence of extramedullary disease (EMD) is associated with poor outcomes for patients with relapsed-refractory multiple myeloma (RRMM) and has been identified as a major risk factor for early progression (≤ 3 months) after CAR T-cell therapy. Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are B-cell maturation antigen (BCMA) targeting CAR T-cell therapies approved for patients with RRMM who have received ≥4 prior lines of therapy (LOT). This is a multicenter retrospective study on the real-world safety and efficacy of commercially available ide-cel and cilta-cel in heavily pretreated RRMM patients with EMD. Methods: Three U.S. academic centers, part of the U.S. Myeloma Innovations Research Collaborative (USMIRC), contributed data to this analysis, which included patients with RRMM who had received an ide-cel or cilta-cel infusion ≥30 days prior to data-cut off (7/1/2023). Baseline patient characteristics were outlined by descriptive analyses. Responses including overall response (ORR), and complete response or better (≥CR) rates were evaluated using the International Myeloma Working Group (IMWG) criteria. Statistical analysis was done with the Fisher's exact test and Kaplan Meier method for progression free (PFS) and overall survival (OS) calculations. Results: A total of 132 patients who received commercial (standard of care) BCMA-directed CAR T-cell therapy between 5/1/2021 and 5/30/2023 were included in this study. Out of these, 64 (48%) patients had a previous history or existing EMD prior to CART infusion. Table 1 summarizes the main patient characteristics and outcomes stratified as EMD and non-EMD groups. Both groups had comparable baseline patient and disease characteristics including median age, ECOG performance status, median bone marrow plasma cell percentage, high-risk cytogenetics, number of prior LOT, refractoriness status prior to CART and type of CAR T-cell product received. CART-related toxicities were comparable between the EMD and the non EMD groups. Cytokine release syndrome (CRS) was seen in 73% (≥ grade 3: 5%) of EMD patients vs 79% (≥ grade 3: 4%) of non-EMD patients (p=0.79). Likewise, immune effector cell-associated neurotoxicity syndrome (ICANS) was noted in 28% (≥ grade 3: 5%) of EMD patients vs 32% (≥ grade 3: 9%) of non-EMD patients (p=0.72). Infections were seen in 39% of the EMD group vs 28% of the non-EMD group (p=0.38). Response rates were also similar between the EMD vs non EMD cohorts: ORR 78% vs 96% (p=0.44); and ≥CR rate 42% vs 51% (p=0.54), respectively. With a median follow up of 7.2 (range 0.5-22.8) months for the entire patient cohort, the estimated median PFS was inferior for the EMD group (6.5 months [95% CI, 5.1-9.6]) compared to the non-EMD group (9.8 months [95% CI, 8.2-16.4]) (p=0.017) (Figure 1). At the time of data cut-off, 43 patients had died, 77% from disease progression, 11.5% from CART-related complications and 11.5% from unrelated causes. The estimated median OS was significantly worse for the EMD group (12.9 months [95% CI, 9.5-NA]) compared to the non-EMD group (19.4 months [95% CI, 1.2-NA]) (p=0.031). Conclusions: This is the largest multicenter retrospective study delineating the real-world outcomes of ide-cel and cilta-cel CAR T-cell therapies in RRMM patients with the high-risk disease feature of EMD. Based on our results, patients with prior history or presence of existing EMD at the time of CART infusion did not have any excessive treatment-related toxicities. However, these patients did experience shorter PFS and OS compared to patients without EMD highlighting the presence of EMD as a risk factor for poor outcomes after CART. Therefore, this group of patients should be considered for pre- and post-CART risk mitigation strategies aiming to prevent disease progression and improve survival outcomes.

Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/ refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience.

While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤3 months after CAR T-cell infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event ≤3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress ≤3 months of infusion (P<0.05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (P<0.001; median PFS for ≥3 factors, 3.2 months vs. 0 factors, 14.1 months). This study helps identify patients at high risk of early progression after CAR T-cell therapy who may benefit from specific interventions pre and post CAR T-cell therpy to improve outcomes.

Analysis of Risk Factors for Early Progression of Prostate Cancer After Initial Endocrine Therapy.

Background: Prolonged androgen deprivation therapy (ADT) in patients with prostate cancer can eventually lead to the development of castration-resistant prostate cancer (CRPC). Once CRPC occurs, the patient's prognosis will be inferior. However, the risk factors for progression to CRPC in a short period of time are unclear. Methods: We retrospectively analyzed prostate cancer patients who received their first ADT between January 1, 2015 and January 1, 2021. The main statistical methods used were a logistic regression model and Kaplan-Meier survival analysis. Results: Among 159 prostate cancer patients initially treated with ADT, 90 were screened for inclusion. Patients who progressed to CRPC after ADT were included in group B and others were included in group A. Group B was divided into group B1 and B2 according to whether CRPC progressed within 18 months. Multi-factor logistic regression analysis showed that the time to PSA nadir (TTN) (p = 0.031) and serum lactate dehydrogenase (LDH) (p = 0.013) were significantly different between Group A and B. TTN (p < 0.001), LDH (p = 0.001) and platelet to lymphocyte ratio (PLR) (p = 0.005) were significantly different between Group B1 and B2. Kaplan-Meier survival analysis and log-rank tests showed that TTN, LDH, and PLR statistically differed in CRPC patients' progression-free survival. The ROC curve showed the AUC value of TTN combined with PLR and LDH increased to 0.958 (95% CI 0.911-0.997, p < 0.001). The Chi-square test showed that the expression of p63 in group A was higher than that in groups B1 (p = 0.002) and B2 (p = 0.001). Conclusion: Lower TTN, higher LDH and PLR were associated with early CRPC occurrence after ADT in hormone-sensitive prostate cancer patients. p63 expression was associated with favorable prognosis in prostate cancer patients.

Risk factors for early progression of diffuse low-grade glioma in adults

BackgroundTo explore the risk factors for early progression of diffuse low-grade glioma in adults.MethodsA retrospective analysis of pathologic and clinical data of patients diagnosed with diffuse low-grade gliomas at Southwest Hospital between January 2010 and December 2014. The progression-free survival (PFS) less than 60 months was classified as the early progress group, and the PFS greater than 60 months was the control group for comparative analysis.ResultsA total of 138 patients were included in this study, including 94 cases of astrocytoma and 44 cases of oligodendroglioma. There were 63 cases with 100% resection, 56 cases with 90–100% resection degree, and 19 cases with resection degree < 90%. The average follow-up time was 60 months, of which 80 patients progressed and 58 patients did not progress. The average progression-free survival was 61 months. The median progression-free survival was 60 months. There were 68 patients with PFS≤ 60 months and 70 patients with PFS > 60 months. The two groups were compared for statistical analysis. In univariate analysis, there were significant differences in tumor subtype (p = 0.005), range (p = 0.011), volume (p = 0.005), location (p = 0.000), and extent of resection (p = 0.000). Multifactor analysis shows tumor location (HR = 4.549, 95% CI: 1.324–15.634, p = 0.016) and tumor subtype (HR = 3.347, 95% CI = 1.373–8.157, p = 0.008), and imcomplete resection is factors influencing early progression of low-grade glioma.ConclusionsLow-grade gliomas involving deep location such as basal ganglia, inner capsule, and corpus callosum are more likely to progress early, while incomplete resection is a risk factor in early progression of astrocytoma.

Early Development of Cardiac Fibrosis in Young Old-Father Offspring.

Cardiac aging is characterized by progressive fibrosis. Epidemiological studies have found that advanced paternal age is associated with an increased risk of heart failure in the next generation. This study is aimed at evaluating the effect of paternal age, in the young male rat progeny, on cardiac phenotype under circulatory stress conditions. Offspring rats were obtained by mating old males (24 months old) with young females (two months old) and by mating young males (two months old) with the same young females. Hypertension was induced in old father offspring (OFO) rats and young old father (YFO) offspring rats using L-NAME (N(ω)-nitro-L-arginine methyl ester). The OFO L-NAME rats showed a high blood pressure phenotype associated with substantial cardiac hypertrophy and an exacerbation of cardiac fibrosis compared to the YFO L-NAME rats. Histological analysis of heart tissue showed an expansion of the extracellular matrix, with fibroblasts displaying markers of epicardial origin (Tcf21, Tbx18, and Wt1) in the OFO group. Moreover, western blot and protein phosphorylation antibody array identified the TGF-β2 receptor pathway as preferentially activated in aged hearts as well as in OFO cardiac tissue treated with L-NAME. In addition, old father offspring rats (OFO+OFO L-NAME) had increased cardiac DNA methylation. In young hypertensive progeny, advanced paternal age at conception may be a risk factor for early progression towards cardiac fibrosis. An intergenerational transmission may be behind the paternal age-related cardiac remodeling in the young offspring.

Prevalence of rapid renal decliner phenotype in south India: A retrospective study

Background and aimsThe burden of chronic kidney disease (CKD) in India is extremely high with the prevalent twin epidemic of diabetes and hypertension. Fast declining phenotype of renal function has yet not been reported in Indian context. Here, we report the prevalence of rapid decliners phenotype in Indian population. MethodsBetween the period 2014–2019, electronic records of 104636 subjects were reviewed. Subjects with serum creatinine values of at least one year apart were selected for further analysis. The study population was categorized based on eGFR, non-decliners < 1 mL/min/1.73 m2/year; progressive decliners 1–5 mL/min/1.73 m2/year and rapid decliners >5 mL/min/1.73 m2/year. Data on diabetes, hypertension, coronary artery disease and cerebrovascular disease were analyzed. ResultsDuring the mean follow up of 4 years, the prevalence of non-decliners, progressive and rapid decliners were 61%, 20% and 19% respectively. Diabetes was higher at 44% in rapid decliners when compared to non-decliners (35.1%); progressive decliners (39.2%). The progression of CKD to end stage renal disease (ESRD) was higher in rapid decliners (32%) in comparison to progressive decliners (19%) ConclusionsThere is a high prevalence of rapid decliner phenotype in India and progression to ESRD is greater and probably is a risk factor for early progression to ESRD.

Parkinson disease-associated cognitive impairment.

Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; amongthem, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment.

Polysplenia Syndrome as a Risk Factor for Early Progression of Pulmonary Hypertension.

Recent progress in surgical and intensive care has improved the prognosis of congenital heart disease (CHD) associated with heterotaxy syndrome. Less is known, however, about pulmonary vascular complications in these patients. Methods and Results: We reviewed medical records of 236 patients who were diagnosed with polysplenia syndrome at 2 institutions for pediatric cardiology in Japan from 1978 to 2015. We selected and compared the clinical records of 16 patients with polysplenia who had incomplete atrioventricular septal defect (AVSD) as the polysplenia group, and 22 age-matched patients with incomplete AVSD without any syndromes including polysplenia as the control group. Although the severity of systemic to pulmonary shunt was not significantly different between the groups, mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance index (PVRI) were significantly higher in the polysplenia group than the control (mPAP, 37.3 vs. 19.1 mmHg, P=0.001; PVRI, 5.7 vs. 1.4 WU∙m2, P=0.014) before surgical intervention. On regression analysis, polysplenia influenced the development of pulmonary hypertension (PH) regardless of age at evaluation or degree of systemic to pulmonary shunt in the patients with incomplete AVSD. Polysplenia syndrome is an independent risk factor for CHD-associated PH. Earlier intervention may be required to adjust the pulmonary blood flow in polysplenia syndrome with CHD to avoid the progression of PH.

[Risk Factors for Early Progression of Carotid Stenosis after Cervical Radiation Therapy].

Carotid stenosis may occur as a late complication following cervical radiation therapy(RT);however, it may also progress in the early post-RT period. This study aimed to characterize the clinical features associated with the early progression of post-RT carotid stenosis. We retrospectively reviewed clinical records of 30 patients who had undergone unilateral or bilateral cervical RT between January 2010 and November 2014. We analyzed the pre- and post-RT stenosis of their carotid arteries using contrast-enhanced computed tomography images. The arteries were classified as progressive or non-progressive according to the presence or absence of stenosis progression within five years after RT. Using univariate and multivariate analyses, we evaluated the following potential clinical risk factors:age;gender;history of hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, or smoking habit;antiplatelet or statin use;radiation dose;and prior presence of carotid stenosis before RT. In total, we reviewed 57 irradiated carotid arteries and identified 9 with early post-RT progression. Carotid stenosis before RT was observed in 88.9% of arteries in the progressive group but only 2% of arteries in the non-progressive group and it predicted progression(univariate and multiple logistic regression analyses, p<0.0001). No other clinical characteristics had a significant association with the progression of carotid stenosis. Prior presence of carotid stenosis may be a risk factor for its early progression after RT. Pre-RT screening of cervical arteries may be useful, and strict management of carotid stenosis is critical in patients with cervical radiation therapy.

Progression to total hip arthroplasty following hip arthroscopy.

Hip arthroscopy is a minimally invasive surgical technique increasingly being used to treat hip pathology. There is evidence that a proportion of patients require total hip arthroplasty in the years immediately following arthroscopy, suggesting that these patients have derived only a limited benefit from the procedure. Identification of risk factors for early progression to hip arthroplasty may enable refinement of hip arthroscopy indications and more informed decision making. The aim of this study is to identify the proportion of patients in a hip arthroscopy cohort who progress to total hip arthroplasty within 2 years of arthroscopy, and to analyse risk factors for this early progression. A retrospective cohort analysis was conducted on all patients who underwent hip arthroscopy at one tertiary institution from 2004 to 2013. Hospital data were linked to the Australian Orthopaedic Association National Joint Replacement Registry in 2016 to identify subsequent hip arthroplasty. There were 989 arthroscopies performed on 947 patients; 447 were female (48.1%), the mean age was 41.1 years (SD: 14.23) and osteoarthritis was present at arthroscopy in 31.5%. Total hip arthroplasty occurred in 129 patients (13%) within 2 years. Multivariable logistic regression revealed osteoarthritis, age >50 years and previous arthroscopy were significant risk factors for arthroplasty within 2 years (adjusted odds ratios (confidence intervals): 4.6 (2.91-7.16), 3.8 (2.44-5.87), 2.5 (1.16-5.81)). Osteoarthritis, older age and history of arthroscopy were independent risk factors for early progression to arthroplasty; these factors should be considered within clinical decision-making, and when discussing potential arthroscopy outcomes with patients.

262O - Rapidly decreasing level of prostate-specific antigen during initial androgen deprivation therapy is a risk factor for early progression to castration-resistant prostate cancer

262O - Rapidly decreasing level of prostate-specific antigen during initial androgen deprivation therapy is a risk factor for early progression to castration-resistant prostate cancer

Rapidly decreasing level of prostate-specific antigen during initial androgen deprivation therapy is a risk factor for early progression to castration-resistant prostate cancer: A retrospective study.

To build a practical model for predicting the progression to castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT).In all, 185 patients with prostate cancer who had received ADT as the primary therapy at our institution, from 2003 to 2014, were retrospectively enrolled. The following clinical variables were included in the analysis: age, clinical tumor, node, metastasis stage, Gleason score, risk groups of prostate cancer, prostate-specific antigen (PSA) at the initiation of ADT, PSA nadir after ADT, velocity of PSA decline, and the time to PSA nadir. Cox proportional-hazards regression models were calculated to estimate effects of these variables on the time of progression to CRPC.On univariate and multivariate analyses, the presence of distant metastasis before ADT (hazard ratio [HR] 6.030, 95% confidence interval (CI) 3.229–11.263, P = .001), higher PSA nadir (HR 1.185, 95% CI 1.080–1.301, P = .001), a velocity of PSA decline >11 ng/mL per month (HR 2.124, 95% CI 1.195–3.750, P = .001), and a time to PSA nadir ≤9 months (HR 0.276, 95% CI 0.162–0.469, P = .004) were significantly associated with an increased risk of progression to CRPC.Patients with a rapidly decreasing PSA level in the initial phase of ADT are more likely to progress to CRPC. Our findings provide a practical approach to screen patients during ADT for early identification of those likely to progress to CRPC, allowing treatment to be modified to improve outcomes.

Higher serum interleukin-17A levels as a potential biomarker for predicting early disease progression in patients with hepatitis B virus-associated advanced hepatocellular carcinoma treated with sorafenib

BackgroundAlthough sorafenib is the only available drug with proven efficacy for patients with advanced hepatocellular carcinoma (HCC), the clinical efficacy of sorafenib is variable and unpredictable. The aim of the current study was to identify potential serum biomarkers predicting cancer progression and overall survival (OS) in patients with hepatitis B virus (HBV)-related advanced HCC treated with sorafenib. MethodsThirty-four patients with HBV-related advanced HCC (modified Union for International Cancer Control [UICC] stage IVa or IVb) treated with sorafenib for more than 4weeks were retrospectively enrolled. Using a Luminex 200 system, 11 cytokines including interleukin-17A (IL-17A) were measured in baseline serum samples prior to sorafenib administration. Several clinical factors and the serum concentrations of the 11 cytokines were analyzed using Cox regression analysis. ResultsIn the analysis of progression-free survival (PFS), older age (year; hazard ratio [HR]=1.07; 95% confidence interval [CI]=1.00–1.15; P=0.046) and higher baseline serum IL-17A level (>1.94pg/mL; HR=19.96; 95% CI=3.32–119.86; P=0.001) were identified as significant risk factors for early progression with good predictive power (Harrell’s C=0.817, standard error estimates (se)=0.085). In the analysis of OS, higher Child-Pugh score (>5; HR=2.35, 95% CI=1.09–5.10, P=0.030) and lower serum baseline fibroblast growth factor-2 level (≤20.57pg/mL; HR=3.24, 95% CI=1.22–8.60, P=0.018) were identified as negative predictive factors for OS, even though the model did not have significant predictive power (Harrell’s C=0.634, se=0.062). ConclusionA higher serum IL-17A level is a potential biomarker for predicting poor PFS in patients with HBV-related advanced HCC treated with sorafenib.

Infection à VIH de l'enfant : quand débuter le traitement antirétroviral ?

Administration of highly active antiretroviral treatment (HAART) has led in the developed world to a dramatic reduction in the incidence of HIV related pediatric mortality. HAART is now the standard-of-care therapy in infected children but the occurrence of short- and long-term drug-related toxic effects and emergence of drug-resistant viral variants temper its success. In children, both CD4 cell percent and viral load have independent predictive value for disease progression, CD4 cell being the stronger predictor of AIDS and death. Concerning children aged 12 months or oder current French recommendations for immediate therapy are based on the presence of clinical symptoms (of categories B or C) or the occurrence of a severe immunodeficiency (CD4 cell percent < 15%). In infants, risk of disease progression is higher and the viral load and CD4 percent are less reliable markers. HAART should theoretically be initiated in all infants in order to prevent HIV encephalopathy and early death. However, viral failure under HAART is often encountered in children less than 12 months because of high levels of replication as well as limited data on pharmacokinetics and drug dosing. A possible alternative approach for infants without risk factor for early progression is to defer HAART under close mentoring.

Early Disease Progression after Intravesical Bacillus Calmette‐Guérin (BCG) Therapy for Superficial Bladder Cancer

Disease progression after Bacillus Calmette-Guérin (BCG) instillation therapy for bladder cancer is not rare. The purpose of this study was to evaluate the outcome of patients treated with BCG for superficial bladder cancer, focusing on the patients who developed invasive disease during follow-up. The possible mechanism and risk factors for early progression after BCG therapy are discussed. A total of 25 patients with superficial bladder cancer (pTa, pT1 and/or pTis) were treated with intravesical BCG instillation (80 mg in 80 ml saline) once a week for eight weeks. Four of the 25 patients received maintenance therapy with BCG (once a month for 3 to 10 months). Patients were followed every three months and underwent cystoscopy, biopsy, and urinary cytology at these intervals. Disease progression was defined as invasion to muscle or prostate, or development of metastatic disease. Clinicopathological features of the patients, especially those with progression, were analyzed. Progression was observed in six of the 25 patients, (including four of 19 patients with carcinoma in situ and two of five patients treated prophylactically with BCG). The average time to progression was 8.7 months. Four patients died of cancer despite intensive treatment. Two patients are alive: one without evidence of disease after cystectomy and the other with metastatic disease. Proper patient selection, careful follow-up, and immediate aggressive therapy in case of progression were considered to be important factors to obtain satisfactory results with BCG therapy for bladder cancer.

Effect of blood pressure and diabetes on stroke in progression

SummaryProgression of acute stroke after arrival at hospital is frequent and the prognosis severe. However, risk factors and mechanisms behind progression are largely unknown. A prospective, community-based study of 868 patients with acute stroke was undertaken to discover factors of importance in the development of stroke in progression.Diagnosis of progression was based on the Scandinavian Neurological Stroke Scale. Patients were divided according to whether progression occurred early (within 36 hours from stroke onset) or late (within the first week from onset). Results were analysed by comparing patients with and without progression. Marked progression developed in 32%. Risk factors for early progression were identified as systolic blood pressure on admission (decreased the relative risk by 0·66 per 20 mm Hg increase, 95% CI 0·55-0·83) and diabetes (increased the relative risk by 1·9, 95% Cl 1·1-3·3). Stroke severity was the only risk factor found in late progression (OR 1·4 per 20-point increase in stroke severity, 95% Cl 1·1-1·7). These relations were independent of age, sex, blood glucose, heart disease, and other stroke risk factors.Early progression is related to systolic blood pressure and diabetes. Late progression is related to initial stroke severity. Although this study does not prove that a causal relationship exists between systolic blood pressure and the development of early progression, such a relationship would, however, explain our findings.