Risk Factors For Disease Progression Research Articles

Association of Multiple High-Risk Factors on Observed Outcomes in Real-World Patients With Advanced Ovarian Cancer Treated With First-Line Therapy.

To identify risk factors for disease progression or death and assess outcomes by risk categories in real-world patients with advanced ovarian cancer. This retrospective study included adult patients from a nationwide electronic health record-derived deidentified database with stage III/IV ovarian cancer who received first-line therapy and had ≥12 weeks of follow-up after index date (end of first-line therapy). Factors predictive of time to next treatment and overall survival (OS) were assessed. Patients were grouped according to the cumulative number of high-risk factors present (stage IV disease, no debulking surgery or neoadjuvant therapy and interval debulking surgery, visible residual disease after surgery, and breast cancer gene [BRCA] wild-type disease/unknown BRCA status), and time to next treatment and OS were assessed. Region of residence, disease stage, histology, BRCA status, surgery modality, and visible residual disease were significant predictors of time to next treatment; age, Eastern Cooperative Oncology Group performance status, disease stage, BRCA status, surgery modality, visible residual disease, and platelet levels were significant predictors of OS (N = 1,920). Overall, 96.4%, 74.1%, and 40.3% of patients had at least 1, 2, or 3 high-risk factors, respectively; 15.7% of patients had all four high-risk factors. Observed median time to next treatment was 26.4 months (95% CI, 17.1 to 49.2) in patients with no high-risk factors and 4.6 months (95% CI, 4.1 to 5.7) in patients with four high-risk factors. Observed median OS was shorter among patients with more high-risk factors. These results underscore the complexity of risk assessment and demonstrate the importance of assessing a patient's cumulative risk profile rather than the impact of individual high-risk factors. They also highlight the potential for bias in cross-trial comparisons of median progression-free survival because of differences in risk-factor distribution among patient populations.

Effect of the Timing of Amubarvimab/Romlusevimab (BRII-196/198) Administration on Progression to Severe Disease in Elderly Patients with COVID-19 Infection: A Retrospective Cohort Study

ObjectiveEarly intervention with neutralizing antibodies is considered to be effective in preventing disease progression in patients with mild to moderate COVID-19 infection. Elderly patients are the most susceptible and at a higher risk of COVID-19 infection. The present study aimed to assess the necessity and possible clinical benefits of the early administration of Amubarvimab/Romlusevimab (BRII-196/198) in the elderly population.MethodsThe present study was designed as a retrospective, multi-center cohort study conducted with 90 COVID-19 patients aged over 60, who were divided into two groups based on the timing of the administration of BRII-196/198 (administration at ≤ 3 days or > 3 days from the onset of infection symptoms).ResultsThe ≤ 3 days group exhibited a greater positive effect (HR 5.94, 95% CI, 1.42–24.83; P < 0.01), with only 2 patients among 21 patients (9.52%) exhibiting disease progression, compared to the 31 patients among the 69 patients (44.93%) of the > 3 days group who exhibited disease progression. The multivariate Cox regression analysis revealed low flow oxygen support prior to BRII-196/198 administration (HR 3.53, 95% CI 1.42–8.77, P < 0.01) and PLT class (HR 3.68, 95% CI 1.37–9.91, P < 0.01) as independent predictors of disease progression.ConclusionsIn elderly patients with mild or moderate COVID-19 disease, who do not require oxygen support and had the risk factors for disease progression to severe COVID-19 disease, the administration of BRII-196/198 within 3 days resulted in a beneficial trend in terms of preventing disease progression.

Unraveling the Molecular and Cellular Pathogenesis of COVID-19-Associated Liver Injury.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) continues to cause substantial morbidity and mortality. Most infections are mild; however, some patients experience severe and potentially fatal systemic inflammation, tissue damage, cytokine storm, and acute respiratory distress syndrome. Patients with chronic liver disease have been frequently affected, experiencing high morbidity and mortality. In addition, elevated liver enzymes may be a risk factor for disease progression, even in the absence of underlying liver disease. While the respiratory tract is a primary target of SARS-CoV-2, it has become evident that COVID-19 is a multisystemic infectious disease. The hepatobiliary system might be influenced during COVID-19 infection, ranging from a mild elevation of aminotransferases to the development of autoimmune hepatitis and secondary sclerosing cholangitis. Furthermore, the virus can promote existing chronic liver diseases to liver failure and activate the autoimmune liver disease. Whether the direct cytopathic effects of the virus, host reaction, hypoxia, drugs, vaccination, or all these risk factors cause liver injury has not been clarified to a large extent in COVID-19. This review article discussed the molecular and cellular mechanisms involved in the pathogenesis of SARS-CoV-2 virus-associated liver injury and highlighted the emerging role of liver sinusoidal epithelial cells (LSECs) in virus-related liver damage.

APOC1 exacerbates renal fibrosis through the activation of the NF-κB signaling pathway in IgAN.

Introduction: IgA nephropathy (IgAN) is the most common disease leading to end-stage renal disease, and tubular fibrosis represents an important risk factor for disease progression. However, research on early molecular diagnostic indicators of tubular fibrosis and the mechanisms underlying disease progression is still lacking. Methods: The GSE93798 dataset was downloaded from the GEO database. DEGs were screened and analyzed for GO and KEGG enrichment in IgAN. The least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms were applied to screen for hub secretory genes. The expression and diagnostic efficacy of hub genes were confirmed by the GSE35487 dataset. ELISA was applied to detect the expression of APOC1 in serum. The expression and localization of hub genes in IgAN were verified by the expression of IHC and IF in human kidney tissues, and the correlation of expression with clinical data was verified in the Nephroseq database. Finally, cellular experiments clarified the role of hub genes in the signaling pathway. Results: A total of 339 DEGs were identified in IgAN, of which 237 were upregulated and 102 downregulated. The KEGG signaling pathway is enriched in the ECM-receptor interaction and AGE-RAGE signaling pathway. APOC1, ALB, CCL8, CXCL2, SRPX2, and TGFBI identified six hub secretory genes using the LASSO and SVM-RFE algorithms. In vivo and in vitro experiments demonstrated that APOC1 expression was elevated in IgAN. The serum concentration of APOC1 was 1.232 ± 0.1812μg/ml in IgAN patients, whereas it was 0.3956 ± 0.1233μg/ml in healthy individuals. APOC1 exhibited high diagnostic efficacy for IgAN (AUC of 99.091%, specificity of 95.455%, and sensitivity of 99.141%) in the GSE93798 dataset. APOC1 expression negatively correlated with eGFR (R 2 = 0.2285, p = 0.0385) and positively correlated with serum creatinine (R 2 = 0.41, p = 0.000567) in IgAN. APOC1 exacerbated renal fibrosis, possibly in part by activating the NF-κB pathway in IgAN. Conclusion: APOC1 was identified as the core secretory gene of IgAN, which was closely associated with blood creatinine and eGFR and had significant efficacy in the diagnosis of IgAN. Mechanistic studies revealed that the knockdown of APOC1 could improve IgAN renal fibrosis by inhibiting the NF pathway, which may be a potential therapeutic target for improving renal fibrosis in IgAN.

Efficacy and Safety of Adintrevimab (ADG20) for the Treatment of High-Risk Ambulatory Patients With Mild or Moderate Coronavirus Disease 2019: Results From a Phase 2/3, Randomized, Placebo-Controlled Trial (STAMP) Conducted During Delta Predominance and Early Emergence of Omicron.

Safe and effective treatments are needed to prevent severe outcomes in individuals with coronavirus disease 2019 (COVID-19). We report results from STAMP, a phase 2/3, multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended half-life monoclonal antibody, for treatment of high-risk ambulatory patients with mild to moderate COVID-19. Nonhospitalized, unvaccinated participants aged ≥12 years with mild to moderate COVID-19 and ≥1 risk factor for disease progression were randomized to receive a single intramuscular injection of 300 mg adintrevimab or placebo. Enrollment was paused due to the global emergence of the Omicron BA.1/BA1.1 variants, against which adintrevimab showed reduced activity in vitro. The primary efficacy endpoint was COVID-19-related hospitalization or all-cause death through day 29 in participants with COVID-19 due to laboratory-confirmed or suspected non-Omicron severe acute respiratory syndrome coronavirus 2 variants. Between 8 August 2021 and 11 January 2022, 399 participants were randomized to receive adintrevimab (n = 198) or placebo (n = 201), including 336 with COVID-19 due to non-Omicron variants. COVID-19-related hospitalization or all-cause death through day 29 occurred in 8 of 169 (4.7%) participants in the adintrevimab group and 23 of 167 (13.8%) participants in the placebo group, a 66% relative risk reduction in favor of adintrevimab (standardized risk difference, -8.7% [95% confidence interval, -14.71% to -2.67%]; P = .0047). Incidence of treatment-emergent adverse events (TEAEs) was similar between treatment groups (33.9% for adintrevimab and 39.5% for placebo). No adintrevimab-related serious TEAEs were reported. Treatment with a single intramuscular injection of adintrevimab provided protection against severe outcomes in high-risk ambulatory participants with COVID-19 due to susceptible variants, without safety concerns. Clinical Trial Registration. NCT04805671.

Management of COVID-19 Infection in a Small Bowel Transplant Recipient: A Case Report

The COVID-19 pandemic has caused millions of people to become infected worldwide. Some patients may have disease progression and may need treatment with an anti-COVID-19 agent, hospitalization, and even intensive care. The risk factors for disease progression include old age, diabetes mellitus, pulmonary disease, cardiac disease, immunodeficiency, and immunosuppressant treatment. Therefore, managing COVID-19 infection in transplant patients under immunosuppressant treatments needs specific consideration, especially the side effects of anti-COVID-19 agents and the interaction between immunosuppressants and anti-COVID-19 agents. In this report, we present the case of a small bowel transplant patient who had a COVID-19 infection. The patient was initially treated for paxlovid, and she developed bloody stools and dizziness. The treatment was then changed to molnupiravir without discontinuation of tacrolimus. The patient recovered smoothly after a 5-day treatment with molnupiravir. Here, we discuss the management experience of such patients and review the relevant literature.

Evaluation of Serum Uric Acid and its Correlation with Decline in Estimated Glomerular Filtration Rate among the Chronic Kidney Disease Patients

Background: Chronic kidney disease is one of the most serious public health burdens globally, with significant morbidity, mortality, and reduced patient life expectancy. Many sub-Saharan African countries face double-burden challenges in the treatment of chronic kidney disease and its complications. This study aims to evaluate serum uric acid and its correlation with estimated glomerular filtration rate, as well as other risk factors among chronic kidney disease patients on follow-up at Jimma University specialised referral hospital. Method: A hospital-based cross-sectional study was conducted at Jimma University Medical Centre from August 6, 2022, to November 13, 2022. Using a consecutive sampling technique, a total of 140 CKD follow-up patients were recruited into the current study. Data were collected using interviewer-based structured questionnaires, record reviews, and physical examinations. The collected data were analysed by SPSS version 25.0. The correlation between eGFR and uric acid concentrations was examined by Pearson’s correlation analyses. Univariate and multivariate linear regression were used to test predictors of serum uric acid in the study participants. Result: A total of 140 study participants were recruited for this study. Subjects included (54.3% [n=76]) men and (45.7% [n=64]) women, respectively. The mean (SD) age of the study subjects was 51.04±9.02 years. The mean value of serum uric acid was 7.2±2.1mg/dl, whereas the mean of estimated glomerular filtration rate (eGFR) was 54.2±31 mL/min/1.73m2. Furthermore, the mean values of serum creatinine and blood urea nitrogen among participants in this study were 3.2±1.4 and 67.8±35.8 mg/dL. In the current study, estimated glomerular filtration rate (eGFR) value was negatively correlated (r=-0.912, P&lt;0.001) with uric acid. However, systolic blood pressure was positively correlated (r=0.584, P&lt;0.001) with uric acid. Moreover, the eGFR value was negatively associated (β=-0.060, P=&lt;0.001) with uric acid among study participants. Conclusion: Based on the current study findings, an increase in serum uric acid was associated with a decrease in eGFR value. Increased serum uric acid, increased body mass index (BMI) and high blood pressure are independent risk factors for disease progression in patients with CKD.

Hemoglobin and neutrophil levels stratified according to International Metastatic Renal Cell Carcinoma Database Consortium risk predict the effectiveness of ipilimumab plus nivolumab in patients with advanced metastatic renal cell carcinoma.

To identify biomarkers associated with the effectiveness of ipilimumab plus nivolumab against advanced metastatic renal cell carcinoma. We retrospectively analyzed the data of 75 patients treated with ipilimumab plus nivolumab at seven hospitals between August 2018 and April 2021. Prognostic biomarkers were assessed prior to initiating treatment with ipilimumab plus nivolumab. Median overall survival and progression-free survival were examined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of disease progression. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors most important for predicting disease progression were determined using classification and regression tree analysis. Median overall survival and progression-free survival were longer in the intermediate IMDC risk group than in the poor IMDC risk group (overall: not reached vs. 18.3 months; progression-free: not reached vs. 13.5 months). The multivariate analysis identified poor IMDC risk as a risk factor for disease progression (hazard ratio 2.61, 95% confidence interval: 1.05-6.51). Based on the results of the classification and regression tree analysis, the cohort was divided into non-anemia, anemia + neutro-Low, and anemia + neutro-High groups. Median overall survival and progression-free survival were longer in the non-anemia and anemia + neutro-Low groups than in the anemia + neutro-High group (overall: not reached vs. 29.3 months vs. 4.3 months: progression-free: not reached vs. 29.0 months vs. 3.9 months). Hemoglobin and neutrophil levels may represent crucial biomarkers for predicting the effectiveness of ipilimumab plus nivolumab therapy in patients with renal cell carcinoma.

The role of polymorphic markers of the &lt;i&gt;WWP2&lt;/i&gt; and &lt;i&gt;GDF5&lt;/i&gt; gene in the progression of gonarthrosis in the population of the Central Chernozem region of Russia

Introduction. Osteoarthritis (OA) is one of the most common diseases of the musculoskeletal system, in the development and progression of which hereditary (genetic) factors play an important role. Aim. To establish the role of polymorphisms of candidate genes rs1060105 and rs56116847 SBNO1, rs6499244 NFAT5, rs34195470 WWP2, rs143384 GDF5 in the progression of knee OA in the population of the Central Chernozem region of Russia. Materials and methods. The sample for the study, including 500 patients with knee OA, was divided into two groups: group 1 – patients with stages 3–4 of the disease according to J. Kellgren – J. Lawrence (n = 325), group 2 – patients with stage 2 (n = 175). The study was carried out in a case-control design. Genotyping of DNA samples was performed using the polymerase chain reaction method of TaqMan probes. The study of associations of polymorphic genetic loci with the progression of gonarthrosis was carried out by the method of logistic regression, taking into account the corrections – age, sex, BMI.Results. The G/G genotype rs34195470 of the WWP2 gene (OR = 0.62, p = 0.029) has a protective role in the progression of the knee OA, the A/G genotype of the same polymorphism is a risk factor for disease progression (OR = 1.65, p = 0.012). Within the framework of the dominant genetic model, significant associations with the progression of gonarthrosis were established for the allele A rs34195470 of the WWP2 gene (OR = 1.61, p = 0.039, pperm = 0.049) and the allele variant G rs143384 of the GDF 5 gene (OR = 0.59, p = 0.024, pperm = 0.024).Conclusion. Genetic risk factors for the development of OA of the knee joint of 3–4 radiographic stages are the allele A and the hepotype A/G rs34195470 of the WWP2 gene. The genotype G/G rs34195470 of the WWP2 gene and the allele G rs143384 of the GDF5 gene are of protective importance in the progression of the disease in the population of the Central Chernozem Region of the Russian Federation.

The Optimal Age Threshold for Stratifying the Risks of Disease Progression in Patients with Highly Suspicious Sub-centimeter Thyroid Nodules.

The study aimed to identify the value and optimal age cutoff to predict the progression of highly suspicious thyroid nodules ≤ 10 mm during active surveillance (AS), and to reveal distinct risk factors in patients of different ages. A total of 779 patients with highly suspicious thyroid nodules were enrolled and followed up by ultrasonography. Locally weighted scatterplot smoothing (LOWESS) and the package 'changepoint' were used to identify the optimal age cutoffs using R. Multivariate Cox regression was performed to identify independent prognostic factors in each patient group divided according to age. Age was an independent predictor of nodule progression (P = 0.038). The optimal age cutoff to stratify the risk of nodule progression was 30 years. Younger patients were more likely to have progression of nodules during AS (P < 0.001), including enlargement of nodule size (P = 0.011) and new lesion occurrence (P < 0.001). Nodule size was identified as a risk factor for disease progression in patients younger than 30 years old (P = 0.008, OR 7.946, 95% CI 1.715-36.820), while multifocality (P = 0.018, OR 2.315, 95% CI 1.155-4.639) and thyroiditis (P = 0.028, OR 2.265, 95% CI 1.092-4.699) were independent predictors in patients over 30 years old. Highly suspicious thyroid nodules ≤ 10 mm in young patients tended to be more progressive. The predictors of disease progression were distinct in patients of different ages.

Real-World Outcomes Following First-Line Treatment in Patients with Advanced Ovarian Cancer with Multiple Risk Factors for Disease Progression who Received Maintenance Therapy or Active Surveillance.

We evaluated real-world outcomes in patients with advanced ovarian cancer (AOC) based on their cumulative risk profile and maintenance therapy (MT) status following first-line (1L) treatment. This retrospective observational study of a nationwide electronic health record-derived de-identified database included adult patients diagnosed with stageIII/IV OC from January1, 2011 to February28, 2021, who received 1L therapy and had ≥ 12weeks of follow-up after the index date (end of 1L therapy). Patients were grouped according to whether they received MT or active surveillance (AS) following 1L treatment and by the cumulative number of risk factors (RF) present (stageIV disease; no surgery/treated with neoadjuvant therapy and interval debulking surgery; had postoperative visible residual disease; and had BRCA wild-type disease/unknown BRCA status). Time to next treatment (TTNT) and overall survival (OS) were assessed with a cloning and inverse probability of censoring (IPC)-weighted Kaplan-Meier method. Among 1920 patients, 22.2% received MT and 77.8% received AS. Median IPC-weighted TTNT and OS were 13.3months (95%CI 11.7-15.8) and 39.1months (95%CI 32.5-48.6) in the MT cohort, respectively, and 8.6months (95%CI 8.0-9.5) and 38.4months (95%CI 36.4-41.0) in the AS cohort, respectively. Almost all patients had ≥ 1 RF (MT 95.3%; AS 96.7%). Median IPC-weighted TTNT was shorter among patients with more RF in both cohorts (MT: 1RF, 19.3months, 95%CI 13.5-37.8; 2RF, 17.2months, 95%CI 12.8-20.2; 3RF, 11.0months, 95%CI 8.2-13.8; 4RF, 7.0months, 95%CI 6.2-8.8; AS: 1RF, 17.7months, 95%CI 13.5-22.3; 2RF, 10.2months, 95%CI 9.1-11.5; 3RF, 6.5months, 95%CI 5.8-7.4; 4RF, 4.1months, 95%CI 3.5-4.5). Regardless of RF number, MT was associated with longer TTNT in real-world patients with AOC.

LBA01-02 IMPACT OF MEDICAL TREATMENT ON STORAGE VS VOIDING SYMPTOMS AND NOCTURIA FREQUENCY: A DYNAMIC NOMOGRAM N=9167 MEN WITH PROSTATIC ENLARGEMENT

You have accessJournal of UrologyCME1 Apr 2023LBA01-02 IMPACT OF MEDICAL TREATMENT ON STORAGE VS VOIDING SYMPTOMS AND NOCTURIA FREQUENCY: A DYNAMIC NOMOGRAM N=9167 MEN WITH PROSTATIC ENLARGEMENT Claus Roehrborn, Juan Manuel Palacios, Chandrashekhar Chavan, Stavros Gravas, Matthias Oelke, Marcio Augusto Averbeck, Arunangshu Biswas, Llenalia María García, and Vanessa Cortes Claus RoehrbornClaus Roehrborn More articles by this author , Juan Manuel PalaciosJuan Manuel Palacios More articles by this author , Chandrashekhar ChavanChandrashekhar Chavan More articles by this author , Stavros GravasStavros Gravas More articles by this author , Matthias OelkeMatthias Oelke More articles by this author , Marcio Augusto AverbeckMarcio Augusto Averbeck More articles by this author , Arunangshu BiswasArunangshu Biswas More articles by this author , Llenalia María GarcíaLlenalia María García More articles by this author , and Vanessa CortesVanessa Cortes More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003360.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: It is unclear how the interaction of clinical covariates modulates medical treatment response in individual profiles of men with lower urinary tract symptoms/benign prostatic enlargement (LUTS/BPE). We developed a predictive analytics solution using baseline characteristics that commonly define patient risk of disease progression to project the change in storage, voiding and nocturia LUTS, in individual profiles receiving placebo (PBO), dutasteride (DUT), tamsulosin (TAM) or DUT/TAM combination therapy (CT). METHODS: A total of 9167 men with LUTS/BPE at risk of progression from three PBO-controlled DUT trials and one comparing DUT, TAM, and CT were included in the analyses to predict response to placebo up to 24 mo and active treatment up to 48 mo. Baseline characteristics included as predictors were: age, International Prostate Symptom Score (IPSS), total prostate volume (PV), maximum urine flow rate (Qmax), prostate-specific antigen (PSA), postvoid residual urine (PVR), α-blocker (AB) usage within 12 mo, and randomized treatment. A generalized least-squares model was developed for longitudinal IPSS storage and voiding sub-scores. For nocturia IPSS-Q7 a Generalized Additive Mixed Model was used to generate predictions. A ‘placebo response’ model was added to benchmark the predicted outcomes to treatment for 2-year f/u. RESULTS: For most profiles, nocturia, voiding and storage symptoms improved significantly with CT compared to DUT or TAM therapies. Higher PSA and PV values predicted a greater improvement in the outcomes explored in DUT compared to PBO. Higher PSA levels predicted a greater improvement in nocturia with all active treatments. Moreover, higher Qmax levels predicted better nocturia and voiding scores with all active treatments. Higher PVR levels were predictive of lower improvements in voiding scores with all active treatments. Likewise, previous use of AB indicates a lesser improvement in nocturia with TAM compared to CT therapy and on the storage scores with all active treatments. Also, higher PV levels had worse voiding scores with TAM in comparison with CT and DUT. The models were deployed in an interactive web app to help visualize and understand results for any possible combination of predictors up to 4 years. CONCLUSIONS: This predictive modelling based on large data sets contributes to understand how risk factors for disease progression interact and affect treatment impact on different type of symptoms, reinforcing the importance of an individualized approach for LUTS/BPE management. Source of Funding: GSK (study 219073) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1176 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Claus Roehrborn More articles by this author Juan Manuel Palacios More articles by this author Chandrashekhar Chavan More articles by this author Stavros Gravas More articles by this author Matthias Oelke More articles by this author Marcio Augusto Averbeck More articles by this author Arunangshu Biswas More articles by this author Llenalia María García More articles by this author Vanessa Cortes More articles by this author Expand All Advertisement PDF downloadLoading ...

Consistent Effects of Early Remdesivir on Symptoms and Disease Progression Across At-Risk Outpatient Subgroups: Treatment Effect Heterogeneity in PINETREE Study.

In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% by day28 in high-risk, non-hospitalized patients. Here we report results of assessment of heterogeneity of treatment effect (HTE) of early outpatient remdesivir, focusing on time from symptom onset and number of baseline risk factors (RFs). PINETREE was a double-blind, placebo-controlled trial of non-hospitalized patients with COVID-19 who were randomized within 7days of symptom onset and had ≥ 1 RF for disease progression (age ≥ 60years, obesity [body mass index ≥ 30], or certain coexisting medical conditions). Patients received remdesivir intravenously (200mg on day1 and 100mg on days2 and 3) or placebo. In this subgroup analysis, HTE of remdesivir by time from symptom onset at treatment initiation and number of baseline RFs was not detected. Treatment with remdesivir reduced COVID-19-related hospitalizations independent of stratification by time from symptom onset to randomization. Of patients enrolled ≤ 5days from symptom onset, 1/201 (0.5%) receiving remdesivir and 9/194 (4.6%) receiving placebo were hospitalized (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.82). Of those enrolled at > 5days from symptom onset, 1/78 (1.3%) receiving remdesivir and 6/89 (6.7%) receiving placebo were hospitalized (HR 0.19; 95% CI 0.02-1.61). Remdesivir was also effective in reducing COVID-19-related hospitalizations when stratified by number of baseline RFs for severe disease. Of patients with ≤ 2 RFs, 0/159 (0.0%) receiving remdesivir and 4/164 (2.4%) receiving placebo were hospitalized; of those with ≥ 3 RFs, 2/120 (1.7%) receiving remdesivir and 11/119 (9.2%) receiving placebo were hospitalized (HR 0.16; 95% CI 0.04-0.73). In the outpatient setting, benefit of remdesivir initiated within 7days of symptoms appeared to be consistent across patients with RFs. Therefore, it may be reasonable to broadly treat patients with remdesivir regardless of comorbidities. ClinicalTrials.gov number NCT04501952.

Influencing factors of efficacy and long‐term use of amrubicin in patients with small cell lung cancer

Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long-term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long-term disease control in patients with recurrent SCLC who would benefit from AMR therapy. The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1-6 cycles (discontinuation group). The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p < 0.001). In AMR therapy for patients with relapsed SCLC, continuation of AMR without dose reduction after the second cycle may contribute to disease control and prolonged survival.

Dual-energy CT quantification of extracellular liver volume predicts short-term disease progression in patients with hepatitis B liver cirrhosis-acute decompensation

BackgroundLiver cirrhosis-acute decompensation (LC-AD) has rapid short-term disease progression and difficult early risk stratification. The purpose is to develop and validate a model based on dual-energy CT quantification of extracellular liver volume (ECVIC-liver) for predicting the occurrence of acute-on-chronic liver failure (ACLF) within 90 days in patients with hepatitis B (HBV) LC-AD.MethodsThe retrospective study included patients with HBV LC-AD who underwent dual-energy CT scans of the liver from January 2018 to March 2022 and were randomized to training group (215 patients) and validation group (92 patients). The primary outcome was the need for readmission within 90 days due to ACLF. Based on the training group data, independent risk factors for disease progression in clinical and dual-energy CT parameters were identified and modeled by logistic regression analysis. Based on the training and validation groups data, receiver operating characteristic (ROC) curves, calibration curves, and decision analysis curves (DCA) were used to verify the discrimination, calibration, and clinical validity of the nomogram.ResultsChronic liver failure consortium-acute decompensation score (CLIF-C ADs) (p = 0.008) and ECVIC-liver (p < 0.001) were independent risk factors for ACLF within 90 days. The AUC of the model combined ECVIC-liver and CLIF-C ADs were 0.893 and 0.838 in the training and validation groups, respectively. The calibration curves show good agreement between predicted and actual risks. The DCA indicates that the model has good clinical application.ConclusionThe model combined ECVIC-liver and CLIF-C ADs can early predict the occurrence of ACLF within 90 days in HBV LC-AD patients.

Real-World Experience of the Comparative Effectiveness and Safety of Molnupiravir and Nirmatrelvir/Ritonavir in High-Risk Patients with COVID-19 in a Community Setting.

Molnupiravir (MOV) and nirmatrelvir/ritonavir (NMV/r) are efficacious oral antiviral agents for patients with the 2019 coronavirus (COVID-19). However, little is known about their effectiveness in older adults and those at high risk of disease progression. This retrospective single-center observational study assessed and compared the outcomes of COVID-19 treated with MOV and NMV/r in a real-world community setting. We included patients with confirmed COVID-19 combined with one or more risk factors for disease progression from June to October 2022. Of 283 patients, 79.9% received MOV and 20.1% NMV/r. The mean patient age was 71.7 years, 56.5% were men, and 71.7% had received ≥3 doses of vaccine. COVID-19-related hospitalization (2.8% and 3.5%, respectively; p = 0.978) or death (0.4% and 3.5%, respectively; p = 0.104) did not differ significantly between the MOV and NMV/r groups. The incidence of adverse events was 2.7% and 5.3%, and the incidence of treatment discontinuation was 2.7% and 5.3% in the MOV and NMV/r groups, respectively. The real-world effectiveness of MOV and NMV/r was similar among older adults and those at high risk of disease progression. The incidence of hospitalization or death was low.

Factors associated with viral rebound among COVID-19 patients receiving oral antivirals

COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound. We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt≥5 units). A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P<0.05). The overall proportion of viral rebound (n=11) was 12.9%, which was more common among patients receiving NMV/r (10 [17.2%] vs. 1 [3.7%], P=0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0-8.0) days after completion of antivirals. Initial lymphopenia (<0.8×109/L) was associated with viral rebound among overall population (adjusted odds ratio [aOR], 5.34; 95% confidence interval [CI], 1.33-21.71), and remained significant (aOR, 4.50; 95% CI, 1.05-19.25) even when patients receiving NMV/r were considered. Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant.

Clinical Diagnostic Value of Serum 25-Hydroxyvitamin D in Severe Fever with Thrombocytopenia Syndrome.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an infectious disease with rapid onset and high case fatality rate. The study was to explore the clinical value by examining the serum level of 25-hydroxyvitamin D (25 (OH) D) in SFTS patients. One hundred and five patients and 156 healthy controls were included. Univariate and multivariate regression analyses were performed to identify independent risk factors for disease progression. Subject operating characteristics (ROC) curves were drawn, and the corresponding area under the curve (AUC) was calculated to assess the sensitivity and specificity of the diagnostic disease. The 25 (OH) D level of disease group was lower than that of healthy control group (22.12 (18.43, 25.86) ng/mL vs 27.36 (23.20, 32.71) ng/mL; P<0.05). The 25 (OH) D level of severe disease group was lower than that of mild disease group (20.55(16.30, 24.44) ng/mL vs 24.94(20.89, 31.91) ng/mL; P<0.05). And there was no significant difference of 25 (OH) D level between the survival group and death group in severe disease group. Multivariate Logistic regression analysis showed that the 25 (OH) D level under 19.665 ng/mL was an independent risk factor for the development of SFTS (OR = 0.901, P=0.040). Furthermore, age more than 68.5 years old and lactate dehydrogenase (LDH) more than 1023.5U/L were independent risk factors for death in severe patients with SFTS. Patients with SFTS have reduced 25 (OH) D level, and 25 (OH) D is a risk factor for disease severity in patients with SFTS. Vitamin D supplementation may be an effective measure to reduce the risk of infection and improve the prognosis.

A new model for predicting adverse outcomes in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive disease leading to ventricular arrhythmias and heart failure. Determining optimal time for heart transplantation (HTx) is challenging; therefore, it is necessary to identify risk factors for disease progression. The study aimed to identify predictors of end‑stage heart failure and to evaluate the role of biomarkers in predicting adverse outcomes in ARVC. A total of 91 individuals with ARVC (59 men; mean [SD] age, 47 [16] years) were included. In all patients, information on medical history was collected, electrocardiography and echocardiography were performed, and serum levels of selected biomarkers (soluble form of the ST2 protein [sST2], galectin‑3 [Gal‑3], extracellular matrix metalloproteinases [MMP‑2 and MMP‑9], N‑terminal pro-B‑type natriuretic peptide [NT‑proBNP], and high‑sensitivity troponin T [hs‑TnT]) were measured. Thereafter, the participants were followed for the primary end point of death or HTx, as well as the secondary end point of major arrhythmic events (MAEs), defined as sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter‑defibrillator intervention. During the median (interquartile range) follow‑up of 36.4 (29.8-41.2) months, 13 patients (14%) reached the primary end point of death or HTx, and 27 (30%) experienced MAEs. The patients who achieved the primary end point had higher levels of sST2, MMP‑2, NT‑proBNP, and hs‑TnT, but not of Gal-3 and MMP-9. Three factors turned out to be independent predictors of death or HTx: higher NT‑proBNP concentration (≥890.3 pg/ml), greater right ventricular end‑diastolic area (≥39 cm2), and a history of atrial tachycardia. None of the biomarkers predicted MAEs. An NT‑proBNP concentration greater than or equal to 890.3 pg/ml, right ventricular end-diastolic area of 39 cm2 or greater, and a history of atrial tachycardia were identified as risk factors for death or HTx in ARVC. Higher levels of sST2, MMP‑2, NT‑proBNP, and hs‑TnT were associated with reaching the primary end point of death or HTx. The biomarkers had no value in predicting ventricular arrhythmias.

Nutritional and prognostic value of bioelectrical phase angle as a potentially modifiable marker in acute myeloid leukemia.

Phase angle (PhA), as measured by bioelectrical impedance analysis, is an important parameter in nutritional assessment and is highly predictive of clinical outcomes in various diseases; however, there is little research on its use in acute myeloid leukemia (AML). Therefore, the present study was conducted to determine the association between PhA and malnutrition and to clarify the prognostic significance of PhA for progression-free survival (PFS) and overall survival (OS) in adult patients with AML (excluding acute promyelocytic leukemia) who were undergoing chemotherapy. A total of 70 patients with newly diagnosed AML were enrolled. After chemotherapy, the nutritional risk for patients with a reduced baseline PhA increased significantly. Disease progression occurred in 28 patients, of which 23 died, with a median follow-up of 9.3 months. A reduced baseline PhA was associated with poor PFS (7.1 months vs. 11.6 months; P=0.001) and OS (8.2 months vs. 12.1 months; P=0.011). A multivariate analysis revealed that a reduced PhA was an independent risk factor for disease progression (hazard ratio, 3.13; 95% CI, 1.21-8.11; P=0.019). Overall, these results suggested that PhA is an effective and sensitive indicator that may provide important nutritional and prognostic information in patients with AML.