Rate Of Progression Research Articles

Patterns of radiological progression in participants (pts) with embolization-eligible hepatocellular carcinoma (HCC) treated with durvalumab (D) + bevacizumab (B) + transarterial chemoembolization (TACE) and placebos + TACE: EMERALD-1 post hoc analysis.

574 Background: EMERALD-1 (NCT03778957) met its primary endpoint, demonstrating improved progression-free survival (PFS) in pts with locoregional HCC treated with D + B + TACE versus placebos (PBO) + TACE (stratified Cox proportional hazards hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.98 [Lencioni R, et al. J Clin Oncol 2024;42(suppl 3). Abs LBA432]). This post hoc analysis assessed outcomes by radiological progression pattern in pts treated with D + B + TACE or PBO + TACE. Methods: Pts included in this analysis received D (1500 mg) or PBO for D (Q4W) in combination with conventional (c)- or drug-eluting bead (DEB)-TACE (investigator choice, 1–4 TACE procedures within 16 weeks). Subsequently, pts received D (1120 mg) + B (15 mg/kg), or PBO for D + B (Q3W). This study analyzed radiological progression patterns at the time of first progressive disease (PD) as assessed by the investigator per modified Response Evaluation Criteria in Solid Tumors. A new lesion was classified as a new intrahepatic lesion (NIH) or new extrahepatic lesion (NEH); tumor growth of existing intrahepatic lesions (increase of ≥20% of an existing target lesion with at least >5 mm absolute increase or unequivocal PD with a non-target lesion) was classified as intrahepatic growth (IHG; categories were not mutually exclusive). Efficacy was assessed by time to progression (TTP). Results: In the D + B + TACE arm, 53.9% of pts had PD, and in the PBO + TACE arm 79.0% of pts had PD. The most common pattern of disease progression across both treatment arms was NIH, occurring in 73 (35.8%) and 107 (52.2%) pts in the D + B + TACE and PBO + TACE arms, respectively, with 31 (15.2%) and 34 (16.6%) pts exhibiting IHG, and 24 (11.8%) and 39 (19.0%) pts exhibiting NEH, respectively. Improved TTP was observed in pts treated with D + B + TACE versus PBO + TACE, regardless of progression pattern (Table). Conclusions: Overall, the rate of progression was lower with D + B + TACE compared with PBO + TACE. The pattern of disease progression observed with D + B + TACE and PBO + TACE was similar, with NIH the most common pattern of progression in both treatment arms. Consistent benefit in TTP was observed with D + B + TACE versus PBO + TACE, regardless of progression pattern. Clinical trial information: NCT03778957 . NIH IHG NEH D + B + TACE (n=73) PBO + TACE (n=107) D + B + TACE (n=31) PBO + TACE (n=34) D + B + TACE (n=24) PBO + TACE (n=39) Median (95% CI) TTP, months 13.7 (10.8–16.5) 8.8 (7.0–10.9) 5.1 (3.0–9.0) 4.3 (2.9–4.8) 6.7 (2.8–16.6) 4.6 (2.9–6.8) HR (95% CI)* 0.78 (0.57–1.07) 0.61 (0.36–1.03) 0.66 (0.36–1.15) *HR and CI were estimated using a Cox proportional hazards model, the CI was calculated using a profile likelihood approach.

Evaluating the effect of a non-linguistic cognitive intervention on functional communication in global aphasia: A case series study.

Global aphasia is a severe communication disorder affecting all language modalities, commonly caused by stroke. Evidence as to whether the functional communication of people with global aphasia (PwGA) can improve after speech and language therapy (SLT) is limited and conflicting. This is partly because cognition, which is relevant to participation in therapy and implicated in successful functional communication, can be severely impaired in global aphasia. Cognitive treatments that aim to improve functional communication for people with aphasia do exist, but few have been trialled with PwGA and no studies have robustly demonstrated gains. This study aimed to explore the effect of a novel non-linguistic cognitive intervention on the functional communication skills of PwGA. A non-linguistic intervention, developed to target cognitive skills underpinning functional communication, was delivered to six participants three times weekly for up to 6 weeks (depending on the rate of progression through the intervention programme). All participants met the criteria for global aphasia following screening with the Western Aphasia Battery Bedside Record Form. A multiple baseline case series design was employed to investigate changes in functional communication using the American Speech and Hearing Association Functional Assessment of Communication (ASHA-FACS). Secondary outcome measures were auditory comprehension and informal tests of non-verbal cognition. Statistical analyses of change after intervention were performed using the Wilcoxon signed-ranks test and weighted statistics. Participants completed the intervention programme in an average of nine sessions. Four out of six participants made statistically significant gains in functional communication as measured by communication independence (amount of assistance or prompting required) on the ASHA-FACS. Five of six participants made statistically significant gains in non-verbal semantics, two in non-verbal reasoning and two in auditory comprehension. The findings provide preliminary evidence that a non-linguistic cognitive intervention delivered with a dose replicable in clinical practice can improve functional communication and non-verbal cognition in some PwGA. This finding contrasts with much existing evidence suggesting that improvements in global aphasia can be achieved only after intensive or prolonged input over many years. What is already known on the subject People with global aphasia (PwGA) have the potential to make impairment level gains after intensive or prolonged speech and language therapy (SLT). However, evidence of functional communication gains is limited. Cognition plays an important role in functional communication, particularly the ability to switch to alternative means of communication and switch modalities. What this study adds Contrary to many previous studies, the findings indicate that PwGA can benefit from SLT and make functional communication gains with a relatively low dose of intervention. The findings highlight cognitive skills that appear relevant to basic functional communication abilities in PwGA. These are: attention, visual perception, semantics and non-verbal problem solving. What are the clinical implications of this work? This work suggests that clinicians should offer cognitive, non-linguistic interventions to PwGA and consider delivering intervention using little to no verbal language.

In vivo imaging markers of glymphatic dysfunction in amyotrophic lateral sclerosis: Analysis of ALPS index and choroid plexus volume.

The glymphatic system, essential for brain waste clearance, has been implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Emerging imaging markers, such as the analysis along the perivascular space (ALPS) index and choroid plexus volume (CPV), may provide insights into glymphatic function, but their relevance to ALS remains unclear. To assess glymphatic dysfunction in ALS patients using the ALPS index and CPV. In this prospective single-center study, we analyzed 51 ALS patients and 51 age- and sex-matched healthy controls (HC). The ALPS index was calculated using diffusion tensor imaging, and 3D T1-weighted MRI was used for automated estimation of CPV and its fraction (CPV/total intracranial volume). Diagnostic performance was assessed using area under the receiver operating curve (AUC). Correlations between imaging markers and clinical parameters were also examined. ALS patients had a significantly lower ALPS index (ALS: 1.45±0.15; HC: 1.55±0.16; p=0.002) and higher CPV fraction (ALS: 0.12±0.04%; HC: 0.10±0.02%; p<0.001). The ALPS index and CPV fraction had AUCs of 0.70 and 0.72, respectively. A significant inverse correlation was observed between the ALPS index and CPV fraction (r=-0.31, p=0.002). Both markers correlated with aging but not with clinical disability or progression rate. This study identifies glymphatic dysfunction in ALS, as evidenced by changes in the ALPS index and CPV. Larger studies are warranted to validate these findings and assess their potential as biomarkers for ALS.

Role and Prognostic Implications of Venous Outflow Assessment in Acute Ischemic Stroke.

The venous outflow profile (VOP) is a crucial yet often overlooked aspect affecting stroke outcomes. It plays a major role in the physiopathology of acute cerebral ischemia, as it accounts for both the upstream arterial collaterals and cerebral microperfusion. This enables it to circumvent the limitations of various arterial collateral evaluation systems, which often fail to consider impaired autoregulation and its impact on cerebral blood flow at the microcirculatory levels. In this narrative review, we will highlight the different parameters and modalities used to assess the VOP in acute ischemia. CT parameters include cortical vein opacification score, interhemispheric difference of composite scores of the draining veins classifications on single-phase CT angiography (CTA), as well as the extent and velocity of optimal cortical venous filling on multiphase CTA. Differences in contrast administration and acquisition time render the single-phase CTA parameters less reliable. Perfusion parameters are semiautomated, thus offering greater reproducibility. These include time to peak and prolonged venous transit. Finally, the venous transit time is an MRI parameter. VOP parameters' significance lies in their potential to predict tissue fate and, subsequently, clinical outcomes. Recent studies indicate that favorable VOP is independently associated with slower rates of infarct edema progression, smaller infarct volumes, and higher rates of functional independence after 90days. Moreover, it is considered a predictor of recanalization success and the first-pass effect during mechanical thrombectomy. Conversely, an unfavorable VOP predicts futile recanalization and indicates a higher risk of reperfusion hemorrhage. Our aim is to explore these prognostic implications and their relevance in determining the utility of intracranial intervention.

A Case of Atypical Neurofibromatous Neoplasm of Uncertain Biologic Potential: Unravelling the Enigma

Neurofibromatoses are a group of genetic disorders that cause tumours to form on the nerve tissue. These tumours can progress to more proliferative lesions and can also eventually become malignant, giving rise to a Malignant Peripheral Nerve Sheath Tumour (MPNST). The authors describe a rare case involving a 27-year-old female who presented with swelling on the left forearm in the surgery Outpatient Department (OPD). The swelling measured 6×5 cm and was noted on the left upper forearm. The overlying skin appeared normal, with no evident pulsations. Notably, a scar mark indicative of a previous surgery for a similar swelling was observed at the same site. The patient reported that the previous swelling was operated 2 years ago. Magnetic Resonance Imaging (MRI) findings indicated fusiform swelling in the mid-forearm, possibly originating from the ulnar nerve with significant involvement of the adjacent structures. This case underscores the complexity and diagnostic challenges associated with such swellings, necessitating thorough examination and ongoing monitoring for timely intervention. This case highlights the importance of thorough clinical evaluation, histopathological examination, and molecular analysis in accurately characterising such tumours, guiding clinical management decisions, and ensuring optimal patient outcomes. The diagnostic evaluation and analysis of such swellings contribute invaluable information regarding their proliferation rate and propensity for malignant progression. This comprehensive understanding aids clinicians in tailoring management approaches that prioritise minimal invasiveness while effectively addressing the potential for malignancy, thus optimising patient care.

Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.

Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression. Most FUS mutations disrupt its nuclear localisation, leading to its cytoplasmic accumulation in the CNS. FUS also forms inclusions in around 5% of patients with the related neurodegenerative condition frontotemporal dementia. However, there are key differences between the two diseases at the genetic and neuropathological level, which suggest distinct pathogenic processes. Experimental models have uncovered potential pathogenic mechanisms in FUS-ALS and informed therapeutic strategies that are currently in development, including the silencing of FUS expression using an intrathecally administered antisense oligonucleotide.

Current status of physicians’ perception of HCC conversion/downstaging therapy: A nationwide survey in China.

585 Background: Conversion or downstaging therapy for intermediate and advanced unresectable hepatocellular carcinoma (HCC) has emerged as a significant exploring area of clinical practice and research in recent years. Nonetheless, there exists considerable variability in both the selection criteria for patients undergoing conversion therapy and the regimens selected for conversion across different regions and medical institutions. The present study aims to elucidate the current clinical application of conversion therapy in China, as well as to identify the considerations that physicians take into account when selecting eligible patients for conversion therapy and determining the appropriate conversion modality. Methods: Physicians meeting predefined inclusion criteria were invited to complete an online questionnaire from January to July, 2024. The collected data were subsequently pooled and analyzed descriptively. Results: A total of 120 valid questionnaires were retrieved, mainly form surgical (69.2%, n=83) and interventional (30.8%, n=37) departments. Generally, the study showed that approximately 51% of stage Ib-IIIa patients will be selected for the treatment goal of conversion or downstaging, and the overall successful rate as meeting criteria for surgical resection after treatment was 36%. Three primary factors were prioritized by physicians for determination of conversion therapy: the type of portal vein tumor thrombus (PVTT) (97%, 116/120), the future liver volume (90%, 108/120), and Child-Pugh classification (90%,108/120). In the specific physician group who selected the following attributes, patients classified as Child-Pugh A (82%, 89/108) or Child-Pugh B7 (66%, 71/108), those with tumor diameter exceeding 5 cm (92%, 98/106) and Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1 (89%, 76/85) were most frequently selected for conversion therapy. Additionally, study showed that patients presenting with Vp1-2 (72%, 83/116) and Vp3 (71%, 82/116) could also be considered for conversion therapy. Currently, the prevalent treatment approach of conversion therapy involves a combination of local and systemic therapies, which is utilized in approximately 73% of cases. Among systemic treatment methodologies, the combination of Lenvatinib and immunotherapy is the most widely adopted by physicians. Besides, higher ORR was the foremost consideration for 83% (99/120) of physicians, followed by rapid response (68%, 82/120), adherence to guidelines and consensus (63%, 76/120), and lower tumor progression rate (58%, 70/120). Conclusions: This study elucidates the current status of conversion therapy for HCC in China. The findings underscore the necessity for optimizing conversion modalities and advancing standardized practices in the application of conversion therapy.

Current trends in blood biomarkers detection and neuroimaging for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and cognitive impairments. A significant challenge in managing PD is the variability of symptoms and disease progression rates. This variability is primarily attributed to unclear biomarkers associated with the disease and the lack of early diagnostic technologies and effective imaging methods. PD-specific biomarkers are essential for developing practical tools that facilitate accurate diagnosis, patient stratification, and monitoring of disease progression. Hence, creating valuable tools for detecting and diagnosing PD based on specific biomarkers is imperative. Blood testing, less invasive than obtaining cerebrospinal fluid through a lumbar puncture, is an ideal source for these biomarkers. Although such biomarkers were previously lacking, recent advancements in various detection techniques related to PD biomarkers and new imaging methods have emerged. However, basic research requires more detailed guidelines on effectively implementing these biomarkers in diagnostic procedures to enhance the diagnostic accuracy of PD blood testing in clinical practice. This review discusses the developmental trends of PD-related blood biomarker detection technologies, including optical analysis platforms. Despite the progress in developing various biomarkers for PD, their specificity and sensitivity remain suboptimal. Therefore, the integration of multimodal biomarkers along with optical and imaging technologies is likely to significantly improve diagnostic accuracy and facilitate the implementation of personalized medicine. This review forms valid research hypotheses for PD research and guides future empirical studies.

Investigation of the association of CTRB2 exon 6 deletion with time to progression and overall survival in pancreatic ductal adenocarcinoma.

770 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and limited treatment options. A 584 bp deletion in CTRB2 , which impairs chymotrypsin B2 function, has been linked to increased PDAC risk. This study investigates the impact of this deletion on progression and survival outcomes in patients with PDAC. Methods: There were 633 patients in whom CTRB2ex6 deletion was genotyped; 263 patients received chemotherapy and had time to progression (TTP) information. TTP was calculated from diagnosis date until earliest of 1) progression date (event), 2) surgery, death, or next chemotherapy date (competing risk), or 3) date last known to be alive (censor). Overall survival (OS) was calculated for the cohort from diagnosis until date of death (event) or date last known to be alive (censor). TTP was analyzed using cumulative incidence methods accounting for competing risks; OS was analyzed using Kaplan-Meier methods. Cox proportional hazard models adjusted for age and sex were used to test associations and compute hazard ratios (HR) and 95% confidence intervals (CI). Results: Median TTP in those with CTRB2ex6 deletion negative carrier status (n=209) was 1.3 years vs 5.9 years for those with positive carrier status (n=54). Estimated 3-year progression rates were 54.2% for patients with no CTRB2ex6 deletions, 43.7% for patients with one deletion (n=48), and 33.3% for patients with two CTRB2ex6 deletions (n=6). TTP was not associated with CTRB2 deletion carrier status (HR: 0.8, 95% CI: 0.6-1.3). Median OS for CTRB2ex6 deletion negative carriers (n=514) was 1.0 year vs 0.9 years for positive carriers (n=119); within deletion carriers, heterozygous carriers (n=110) had a median OS of 0.9 years, and homozygous carriers (n=9) had a median OS of 2.6 years. OS was not associated with CTRB2 deletion carrier status (HR: 1.0, 95% CI: 0.9-1.3). Conclusions: Although we did not detect statistically significant differences in TTP and OS by CTRB2ex6 deletion carrier status, there was an interesting trend toward longer TTP and OS in the small number of patients who carried homozygous CTRB2ex6 deletions. Larger studies are warranted to validate these findings.

Current status and treatment outcomes of intraductal papillary mucinous carcinoma in Korea: A multi-center cohort study.

812 Background: The spectrum of intraductal papillary mucinous neoplasm (IPMN) varies from benign cysts to intraductal papillary mucinous carcinoma (IPMC). There is a lack of large-scaled data on IPMC and high-grade dysplasia. We aimed to study the real-world status and treatment outcomes of IPMC in South Korea. Methods: This is a retrospective, multicenter study conducted in South Korea. We reviewed the electronic medical records of patients who were histologically diagnosed with IPMC or high-grade (HG) dysplasia between 2011 and 2020, and analyzed the baseline characteristics, treatment patterns, and survival. Results: A total of 388 patients were eligible from six institutes (145 female [37%]; median age 67.8; 259 IPMC [67%] vs 129 HG dysplasia [33%]). The median overall survival for IPMC patients was 75 months, compared to 133 months for HG dysplasia. In IPMC group, 217 (84%) were underwent surgical resection and 42 (16%) did not underwent surgery due to general condition or advanced stage whose median overall survival was 83 months and 49 months respectively. In resected IPMC, 104 (48%) received adjuvant chemotherapy (gemcitabine single 48%, 5FU+leucovorin 33%, others 19%) and 66 (30%) experienced recurrence and median recurrence-free survival (RFS) was 20 months. Among IPMC group, 11 (4.2%) was in advanced stage and eight of those received palliative chemotherapy (FOLFIRINOX 62.5%; gemcitabine single 25%; gemcitabine with erlotinib 12.5%). In HG dysplasia, 108 (84%) patients underwent surgery, and 21 (16%) patients did not undergo surgery whose OS were 171 and 133 months, retrospectively. In patients with resected HG dysplasia, 29 (27%) experienced recurrence and median RFS was 21 months. Conclusions: IPMC generally showed longer survival and a lower recurrence rate than those of historical data in PDAC, with HG dysplasia demonstrating even better outcomes. In real world, similar chemotherapy regimens used for PDAC were applied to IPMN patients. Treatment status of intraductal papillary mucinous carcinoma and high-grade dysplasia. IPMC(259) IPMN-HG(129) Total(388) Median overall survival (month) 75 133 85 Treatment OP 217(84%) 108(84%) 325(84%) Adjuvant chemotherapy 104(48%) 19(18%) 123(38%) Recurrence rate 66(30%) 29(27%) 95(29%) Median recurrence-free survival (month) 20 19 21 Palliative chemotherapy 8(3%) NA Progression rate 5(63%) NA Progression-free survival (month) 13 NA

The prevalence and 6-year incidence of myopic tessellation in a Chinese rural adult population: the Handan Eye Study

PurposeTo describe the prevalence and the cumulative 6-year incidence of fundus tessellation in a rural Chinese adult population.MethodsThe Handan Eye Study was a population-based longitudinal study, with 6830 eligible subjects included in the baseline period, and 5394 subjects (follow-up rate: 85.3%) took part in the follow-up study. Participants had detailed eye examinations and physical examinations; a detailed questionnaire was also well administered. Fundus tessellation was defined as well-defined choroidal vessels that can be observed clearly around the fovea as well as around the arcade vessels.ResultsAmong 6830 subjects who participated in the baseline study, the prevalence of fundus tessellation was 9.89% (95%CI: 9.22-10.58%). The prevalence of fundus tessellation increased with age; that of subjects aged younger than 50 years and those aged 50 years or older was 2.5% and 14.5%, respectively. Six years later, the cumulative 6-year incidence of fundus tessellation was 1.21% (95%CI: 1.03-1.40%). Similarly, the incidence of fundus tessellation also increased with age; that of participants aged younger than 50 years and those aged 50 years or older was 0.20% and 1.86%, respectively. The progression rate of fundus tessellation in those with fundus tessellation at baseline was 1.5% (95% CI: 0.82%, 2.38%). By multivariable analysis, subjects being older (OR: 1.079, P < 0.001) and havingβ-parapapillary atrophy at baseline (OR: 2.657, P = 0.002) were associated with a higher risk of incidence of fundus tessellation.ConclusionsThe prevalence and 6-year incidence of fundus tessellation were 9.89% and 1.21% in rural Chinese adults aged 30 + years, respectively. The progression rate in participants with fundus tessellation indicates the importance of regular follow-up for these patients.

Progression of the Residual Lesion in Cavernous Sinus Extra-Axial Cavernous Hemangioma After Surgery.

Our study aimedto investigate the factors associated with residual cavernous sinus extra-axial cavernous hemangiomas (ECHs) progression after surgery. This retrospective study consecutively included patients of cavernous sinus ECHs with incomplete lesion resection from February 2012 to January 2024. The progression of the lesions was defined as new lesions or a growth of residual lesion (≥ 10% increase in volume). Cox regression analysis was used to determine factors associated with residual lesion progression. Kaplan-Meier analysis was conducted to estimate the cumulative incidence of residual lesion progression. Sixty patients were included in this study. During the follow-up, there were 31 (51.7%) residual lesions underwent progression, whereas 29 (48.3%) patients were nonprogressive. Multivariate Cox analysis showed that the homogeneous enhancement lesion was correlated with the residual lesion progression (HR, 8.17 [95% CI, 1.03-64.58]; p = 0.046). Kaplan-Meier survival analysis indicated that the rate of homogeneous enhancement lesion progression (3.7 per 10 person-years) was significantly higher than that of the heterogeneous enhancement group (0.5 per 10 person-years; p = 0.019). Fourteen of the 31 patients with lesion progression underwent radiotherapy, and all of them experienced control over the progression of their lesions. This study found thatend-of-treatment residual lesions are not rare in patients with cavernous sinus ECHs and the MRI feature is helpful to predict the progression of residual lesions.

Prediction potential of serum sulfatide levels at diagnosis for end-stage kidney disease progression in ANCA-associated vasculitis.

The aim was to investigate the ability of serum sulfatide levels at diagnosis to reflect the cross-sectional activity and further longitudinally predict the occurrence of end-stage kidney disease (ESKD) during the follow-up period in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), regardless of kidney involvement at diagnosis. This study included 67 patients first diagnosed with AAV with available clinical data, including Birmingham Vasculitis Activity Score (BVAS), erythrocyte sedimentation rate, C-reactive protein, and blood samples at diagnosis. Serum sulfatide levels were assessed using stored serum samples at the time of diagnosis. The median age of the 67 patients (40.3% men and 59.7% women) was 61.0 years. During follow-up, 10 (14.9%) patients progressed to ESKD, and 4 (6.0%) died. Serum sulfatide levels significantly correlated with Five-Factor Score (r = -0.242), erythrocyte sedimentation rate (r = -0.315), and renal manifestation of the BVAS items (r = -0.296), but not BVAS at diagnosis. The cutoff of serum sulfatide levels at diagnosis for ESKD progression was 332.5 pg/mL. However, no significant cutoff of serum sulfatide levels for all-cause mortality was obtained. Patients with serum sulfatide levels ≤ 332.5 pg/mL at diagnosis exhibited both significantly higher frequency of ESKD progression (22.7% vs 0%, P = .012) and lower ESKD-free survival rate than those without (P = .011). This study highlighted the clinical usefulness of measuring serum sulfatide levels at the time of diagnosis as a biomarker to predict ESKD progression in patients with AAV regardless of kidney involvement at diagnosis.

Prognostic significance of NT-proBNP levels in patients treated with empagliflozin.

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been added to the mainstay of treatment for chronic heart failure. Recent studies suggest that empagliflozin may also reverse cardiac remodeling in heart failure by reducing N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. In our study, we wanted to show the decrease in NT-proBNP levels, which is an indicator of poor prognosis in heart failure, and to see if there was a decrease in the rate of renal progression in patients with HF after empagliflozin use. Patients with type 2 diabetes mellitus and heart failure using empagliflozin were selected from the system and 456 patients were found. Patients were divided into two groups: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). The patients were divided into two groups according to their NT-proBNP levels at the beginning of the drug and on the 90th day. The laboratory data were analyzed at the time of drug initiation and at day 90. There was a statistically significant difference between baseline and day 90 HbA1C and NT-proBNP levels (p < 0.001), (p < 0.001). NT-proBNP and creatinine levels at baseline and day 90 were significantly higher in patients with HFrEF than in those with HFpEF (p < 0.001). According to the multivariate analysis, patients with HFrEF were 11.42 times more likely to have an NT-proBNP change above 300 pg/mL than patients with HFpEF (OR: 11.42, p = 0.028). In our study, a significant reduction in NT-proBNP and HbA1C levels was observed, while renal function was preserved.

P-2018. Nirmatrelvir versus Short-Course Remdesivir for Mild-to-Moderate COVID-19 in High Risk Hospitalized Patients: A Propensity Score-Matched Study

Abstract Background As the Coronavirus disease 2019 (COVID-19) has evolved, patients often present with mild-to-moderate disease as opposed to severe disease that was seen earlier in the pandemic. Two previously published studies (PINETREE and EPIC-HR) evaluated treatment options in the outpatient setting for patients with mild-to-moderate disease. These studies may provide insight into how patients with similar disease presentation may be treated in the inpatient setting. The purpose of this study was to evaluate the use of nirmatrelvir (N/R) and short-course remdesivir in high-risk patients hospitalized with mild-to-moderate COVID-19. Clinical Outcomes in the Propensity-Matched Cohort Methods This was a single-center, retrospective cohort study including adult patients hospitalized for mild-to-moderate COVID-19 between January 2021 and December 2023. Patients were grouped by treatment received (N/R or short-course [3-day] remdesivir). They were excluded if they received additional COVID-19 therapies, did not receive the appropriate regimen or were treated prior to hospitalization. Patients were compared by treatment received after propensity score-matching based on baseline characteristics. The primary endpoint assessed was the need for oxygen support. Exploratory endpoints included need for mechanical ventilation, length of stay, 30-day readmission, and mortality. Results Eight-hundred and fifty-six patients were initially screened. After exclusions and propensity score-matching, a total of 75 matched pairs (N=150) were included in the analysis. Patients had an average of three comorbidities or high risk features for COVID-19 progression, most commonly age greater than 60 years, BMI over 25 kg/m2, hypertension, and diabetes. There was no difference in the primary outcome of need for oxygen support in the short-course remdesivir group compared to the N/R group (14 [19%] vs 7 [9%], respectively; p=0.100). There was also no difference in length of stay between the two groups (5 [3, 7] vs 4 [2, 7] days, respectively; p=0.068). All additional endpoints were similar between short-course remdesivir and N/R. Conclusion Patients at high-risk of progression with mild-to-moderate COVID-19 that received N/R or short-course remdesivir had similar rates of disease progression, length of stay, readmissions, and mortality. Disclosures Jonathan Edwards, PharmD, BCPS, BCGP, BCIDP, Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria

Extracranial carotid plaque calcification and its association with risk factors for cerebrovascular events: insights from the ANTIQUE study

IntroductionExtracranial carotid calcification is a common marker of advanced atherosclerosis. However, its impact on stroke risk is not consistent across studies, and examining the type of calcification and the presence of systemic diseases might be helpful. We aimed to investigate extracranial carotid calcification and its association with risk factors for ischemic cerebrovascular diseases.Materials and methodsAmong 1,863 consecutive patients in the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the Carotid Bifurcation Plaque Study (ANTIQUE), 132 symptomatic or asymptomatic patients (177 carotid plaques) with &amp;gt;30% carotid stenosis examined through computed tomography (CT) and magnetic resonance imaging (MRI) were included. Statistical data were assessed using the χ2-test, Fisher’s exact test, t-test, and Mann–Whitney test to investigate the calcification risk factors.ResultsCompared to the absence of calcifications, spotty calcifications were associated with male sex [odds ratio (OR): 3.72, 95% confidence interval (CI): 1.06–13.05], while large calcifications were associated with older patients (OR: 1.60 per 5 years of age, 95% CI: 1.20–2.13). Large calcifications were also strongly associated with coronary heart disease (OR: 4.07, 95% CI: 1.15–14.44) and atrial fibrillation (p = 0.025). In comparison between only spotty and large calcifications, spotty calcifications were associated with male sex (OR: 3.72, 95% CI: 1.06–13.05), smoking (p = 0.020) in more significant quantities (p = 0.014), and lipid plaque (p &amp;lt; 0.001), while large calcifications with contralateral stenosis degree (p = 0.044). No significant relationship was found between cerebrovascular events and the type of calcification.ConclusionAlthough the presence and type of extracranial carotid calcification were not related to ipsilateral ischemic events, large calcifications were strongly associated with coronary heart disease and atrial fibrillation.Clinical trial registrationClinicalTrials.gov, identifier NCT02360137.

A new perspective on mixed moderate aortic valve disease

Abstract Background Mixed aortic valve disease (MAVD) is common in patients with aortic valve disease. Some studies suggest that outcomes of mixed moderate aortic stenosis and regurgitation (ASR) are similar to severe aortic stenosis (AS). However, there is limited data on moderate ASR in the Asian population. This study aims to analyze the characteristics and outcomes of MAVD at our center and compare them with isolated moderate AS and severe AS to determine the prognosis of MAVD. Methods This retrospective study collected MAVD patients from a single tertiary center from January 2000 to January 2023 (n=1452). Patients with severe aortic valve stenosis and/or regurgitation, left ventricular ejection fraction (LVEF) ≤40%, other significant valve disease, previous valve surgery, and age &amp;lt;18 years were excluded. Eventually, we identified 55 patients with moderate ASR (mean aortic peak velocity 3.7 ± 0.6 m/s, mean pressure gradient 31.0 ± 11.0 mmHg, aortic valve area 1.3 ± 0.2 cm², AR vena contracta width 0.4 ± 0.1 cm). We compared them with the isolated moderate AS group (n=648) and severe AS group (n=749). We analyzed the outcomes of AVR and mortality across the three groups. In a sub-analysis, AVR rates were compared between the moderate ASR and moderate AS groups. Results Mean age was the lowest in the moderate ASR group (63.7±13.2 years) compared to the moderate AS group (72.2±10.8 years) and severe AS group (72.6±10.5 years, p&amp;lt;0.001). The proportion of males was similar among the three groups. In moderate ASR group, the etiology of valve was identified as 21.8% of bicuspid valve (12/55), 25.5% of rheumatic valve (14/55) and 50.9% of degenerative trileaflet valve (28/55). (Table1) Mean follow-up duration was 4.15 ± 4.02 years. In outcome, the mortality showed similar between the moderate ASR group and moderate AS group, but significant higher in severe AS group in time-varying adjusted cox regression analysis. The cumulative incidence of AVR was higher in the moderate ASR group by the Kaplan-Meier curve (p=0.025, Figure). Freedom from AVR in the moderate ASR group was 71% at 3 years, 61% at 5 years and 54% at 7 years, indicating more slow progression than previous study. Conclusions In this study, mortality rates between the moderate ASR and the moderate AS groups were similar, but the AVR rates were higher in the moderate ASR group. Compared to previous studies, differences in etiology of the valve and ethnicity may affect the slow progression rate of moderate ASR. Further studies with larger cohorts are needed in the future.

Impact of Sexual Dimorphism on Therapy Response in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: From Conventional and Nutritional Approaches to Emerging Therapies

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a spectrum of liver disease ranging from hepatic fat accumulation to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma in the absence of excessive alcohol consumption. MASLD is characterized by substantial inter-individual variability in terms of severity and rate of progression, with a prevalence that is generally higher in men than in women. Steroids metabolism is characterized by sexual dimorphism and may have an impact on liver disease progression; indeed, several therapeutic strategies targeting hormone receptors are under phase 2/3 development. Despite the fact that the importance of sexual dimorphism in the setting of MASLD is well recognized, the underlying molecular mechanisms that can potentially drive the disease toward progression are not clear. The aim of this review is to delve into the crosstalk between sexual dimorphism and steroid hormone perturbation under nutritional and pharmacological intervention.

Refining MR-guided thermal ablation for HCC within the Milan criteria: a decade of clinical outcomes and predictive modeling at a single institution

BackgroundThe appropriateness of ablation for liver cancer patients meeting the Milan criteria remains controversial.PurposeThis study aims to evaluate the long-term outcomes of MR-guided thermal ablation for HCC patients meeting the Milan criteria and develop a nomogram for predicting survival rates.MethodsA retrospective analysis was conducted from January 2009 to December 2021 at a single institution. Patients underwent MR-guided thermal ablation. Factors influencing progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate Cox regression and stepwise regression. A nomogram was developed for survival prediction, followed by risk stratification and internal validation. Adverse events (AEs) were also analyzed.ResultsA total of 181 patients were included, with a mean follow-up of 73.8 ± 31.7 months. The cumulative local tumor progression rates at 1, 3, and 5 years were 0.80%, 1.27%, and 1.86%, respectively. The 1-, 3-, and 5-year PFS rates were 81.8%, 57.4%, and 38.1%, and OS rates were 98.3%, 87.8%, and 62.9%. Poorer outcomes were associated with age ≤ 60 years, tumor size > 2 cm, multiple tumors, cirrhosis, proximity to major vessels, and narrow ablation margins (P < 0.05). The nomogram accurately predicted 3- and 5-year survival, and internal validation confirmed the results. AEs occurred in 33.7% of patients, with pain being the most common.ConclusionMR-guided ablation is effective for HCC patients within the Milan criteria, especially for those with smaller tumors and better liver function. The nomogram and risk stratification model are valuable tools for predicting patient outcomes and guiding treatment.

Studying Alzheimer’s disease through an integrative serum metabolomic and lipoproteomic approach

BackgroundAlzheimer’s disease (AD) is the most frequent neurodegenerative disorder worldwide. The great variability in disease evolution and the incomplete understanding of the molecular mechanisms underlying AD make it difficult to predict when a patient will convert from prodromal stage to dementia. We hypothesize that metabolic alterations present at the level of the brain could be reflected at a systemic level in blood serum of patients, and that these alterations could be used as prognostic biomarkers.MethodsThis pilot study proposes a serum investigation via nuclear magnetic resonance (NMR) spectroscopy in a consecutive series of AD patients including 57 patients affected by Alzheimer’s disease at dementia stage (AD-dem) and 45 patients with mild cognitive impairment (MCI) due to AD (MCI-AD). As control group, we considered 31 subjects with mild cognitive impairment in whom AD and other neurodegenerative disorders were excluded (MCI). A panel of 26 metabolites and 112 lipoprotein-related parameters was quantified and the logistic LASSO regression algorithm was employed to identify the optimal combination of metabolites-lipoproteins and their ratios to discriminate the groups of interest.ResultsIn the training set, our model classified AD-dem and MCI with an accuracy of 81.7%. These results were reproduced in the validation set (accuracy 75.0%). Evolution of MCI-AD patients was evaluated over time. Patients who displayed a decrease in MMSE < 1.5 point per year were considered at lower progression rate: we obtained a division in 18 MCI-AD at lower progression rate (MCI-AD LR) and 27 at higher progression rate (MCI-AD HR). The model calculated using 4 metabolic features identified MCI-AD LR and MCI-AD HR with an accuracy of 73.3%.ConclusionsThe identification of potential novel peripheral biomarkers of Alzheimer’s disease, as proposed in this study, opens a new prospect for an innovative and minimally invasive method to identify AD in its very early stages. We proposed a novel approach able to sub-stratify MCI-AD patients identifying those associated with a faster rate of clinical progression.