Risk Factors For Disease Progression Research Articles

Abstract 4117032: Investigating the natural history and risk factors underlying deterioration in early-stage hypertrophic cardiomyopathy: findings from SOLENOID

Background: Understanding the natural history and factors contributing to heterogeneous outcomes in patients with early-stage hypertrophic cardiomyopathy (HCM) is crucial to improving patient management. Aim: Utilizing a real-world data cohort spanning multiple centers, we described the natural history of early-stage HCM patients and identified risk factors for disease progression. Methods: SOLENOID is an observational study conducted in five academic centers (two in France, UK, Spain and the US). Inclusion criteria were patients with confirmed HCM seen between 2010 and 2022 in NYHA class I, or in “early stage” NYHA class II (defined by an NT-pro BNP<300 pg/ml, resting or provoked LVOT<50 mmHg, LAVi<35 ml/m2, E/e’<14, without a history of atrial fibrillation (AF), and not on HCM-specific therapy). The endpoint was a composite of NYHA class worsening, new onset of AF and cardiovascular hospitalization. To identify risk factors, univariate analyses were conducted in each center, and then aggregated through a meta-analysis. Results: A total of 1044 patients were included with a median follow-up of 3.9 years (IQR 1.5-7.0). The mean age was 53±16 years, with 30% females and 42% of NYHA I were treated with beta-blockers. Genetic tests in 57% of patients revealed mutations, primarily in MYBPC3 (29%) and MYH7 (12%). During follow-up, the composite endpoint has an incidence of 27% and 41% at 3 and 5 years. The main contributor was NYHA class worsening with an incidence of 24% and 35% at 3 and 5 years. AF at inclusion (log-HR=1.56, p<0.001), baseline level of NT-proBNP (log-HR=0.75, p<0.001) and age at inclusion (log-HR=0.24, p=0.005) were the main predictors of the composite endpoint. Conclusion: Nearly 30% of the early-stage HCM patients experienced disease progression within a 3 year follow-up period, highlighting a medical unmet need. Further studies are needed to assess whether the population characterized by elevated NT-proBNP, or pre-existing AF at inclusion, may benefit from more intensive surveillance and, in future HCM-specific therapy.

Predictors of poor outcomes in juvenile dermatomyositis: what do we know? A narrative review.

Juvenile dermatomyositis (JDM) is a rare chronic systemic inflammatory disorder with a highly variable clinical course. It is important to identify the patients at risk of developing more severe disease. However, based on the existing literature, there is a lack of data regarding predictors of poor outcomes. Obtaining knowledge about clinical and laboratory risk factors for disease progression and severity at an earlier stage of the disease could potentially lead to a better long-term prognosis for patients with JDM. A narrative review with the aim of identifying risk factors for poor outcomes in patients with JDM, such as death, severe disease, refractory disease, and functional impairment, was conducted. A total of 27 articles was included. Certain clinical manifestations and immunology features appear to worsen the prognosis in children with JDM. The recognition of these risk factors is essential for all pediatric rheumatologists as it allows the earlier identification of patients with potentially worse outcomes. These patients should receive closer follow-up and aggressive and individualized therapy in order to reduce their morbimortality. Additional research is needed not only to identify more predictors of worse outcomes but also to identify more effective treatment approaches targeted toward these patients.

Importance of driver gene mutation assessment and targeted therapy for patients with early‑stage non‑small cell lung cancer and non‑R0 resection.

Patients with non-small cell lung cancer (NSCLC) and incomplete resection have poor clinical outcomes. The present study aimed to identify risk factors for disease progression and mortality. A total of 65 patients with early-stage NSCLC that underwent operation but had a non-R0 resection between August 2011 and December 2020 were included in the present study, and the clinicopathological features and driver gene mutation status were analyzed. The median follow-up time was 36.2 months; 39 patients (60.0%) experienced disease progression and 3 patients (4.6%) died. In total, 22 patients (33.8%) harbored mutations in driver genes. Multivariate analysis demonstrated that the presence of driver gene mutations was associated with an increased risk of disease progression [adjusted odds ratio, 24.08; 95% confidence interval (CI), 2.77-209.01; P=0.004]. Tumors classed as Eastern Cooperative Oncology Group performance status 2 [adjusted hazard ratio (HR), 3.49; 95% CI, 1.10-11.03; P=0.033], stage II-IIIB tumors (adjusted HR, 2.55; 95% CI, 1.06-6.17; P=0.037) and the presence of a driver gene mutation (adjusted HR, 3.28; 95% CI, 1.55-6.94; P=0.002) were associated with a significantly reduced progression-free survival (PFS). Driver gene-targeted therapy was associated with an increased post-progression survival for patients that were reported to have disease progression (adjusted HR, 0.38; 95% CI, 0.16-0.91; P=0.030). There was no significant impact of driver gene mutation status on the overall survival (OS) of patients. Although the presence of a driver gene mutation was associated with an increased risk of disease progression and a reduced PFS, it was demonstrated that patients with disease progression may benefit from driver gene-targeted therapy, as patients with driver gene-targeted therapy had a similar OS compared with that of patients with a driver gene-negative or unknown status. Therefore, early comprehensive analysis of driver gene mutation status may be recommended for early-stage NSCLC cancer patients experiencing non-R0 resection.

Natural language processing realises the potential of electronic health records: identifying risk factors for disease progression and major adverse limb events in intermittent claudication

Abstract Background/Introduction Peripheral Arterial Disease (PAD) is a common pathology, affecting 4.5% of the UK population. Symptomatic PAD manifests as intermittent claudication (IC). Predictors of IC progression to Chronic-Limb-Threatening Ischaemia (CLTI) and complications including Major Adverse Limb Events (MALE), such as smoking history and diabetes, have been described previously in resource-intensive cohort studies. Novel Natural Language Processing (NLP) approaches transform routinely collected, unstructured health records into datasets for real-world analysis of PAD. Purpose This study leverages NLP based interrogation of electronic health records to efficiently identify risk factors for disease progression and MALE in patients presenting with IC. Methods A retrospective cohort study of patients with PAD at a large, tertiary vascular referral centre identified using the SNOMED terms of IC in the Medcat-NLP-AI toolkit. Demographics, Index of Multiple Deprivation (IMD), and indicators of disease progression, and revascularisation and amputation (MALE) were analysed using Kaplan-Meier survival and Cox Proportional-Hazards analysis. Results 5,027 patients (Mean age 73.7(61.8-85.6), Males 66.1% (n=2,781) were identified. Self-reported population ethnicity was 4.72% Asian, 15.5% Black, 79.7% White. All-cause mortality was 19.5% (n=979) after 10 years of follow-up, with 5.85% of patients progressing to CLTI (n=294). 2.32% of Asian patients, 5.78% of Black patients and 5.04% of White patients progressed to CLTI, respectively. 5.09% of Asian patients, 8.99% of Black patients, and 7.36% of White patients underwent amputation. Multivariate analysis of risk factors for progression to CLTI, demonstrated that diabetes (HR 2.36, 95%CI: 1.22 - 4.48, p = .01) and smoking history (HR 1.76, 95%CI: 1.19 - 2.59, p = .004) independently predicted progression. No risk factors for MALE reached significance. Conclusions Diabetes and smoking behaviour are well-described in the literature as risk factors for progression to CLTI. This study demonstrates the utility of NLP as a resource efficient, validated, methodological tool. Disparities in MALE may exist between patients within a universal healthcare system, although our sample size was insufficient to demonstrate statistical significance. A larger, multicentre analysis is warranted. NLP represents a valuable tool for efficiently identifying and analysing risk factors for PAD progression and holds potential to refine management algorithms.KM curves of CLTI-free survival (DM)

The rate of change in clinical indicators can predict the progression of hepatitis B virus-related acute-on-chronic preliver failure.

The objective of this study was to investigate the predictors and predictive model construction of the progression of HBV-Pre.Acute-on-chronic liver failure (ACLF), a total of 133 patients with HBV-Pre.ACLF was divided into the progressive group (52 patients) and the recovery group (81 patients) according to whether they progressed to ACLF or not. The clinical parameters N%, L%, PLT, ALT, TBiL, ALB, Cre, Na, NH3, CRP, AFP, prothrombin time (PT), international normalized ratio (INR), FIB, and their rate of change at baseline were analyzed in the 2 groups. The independent risk factors for HBV-Pre.ACLF progression was found by univariate and multivariate analyses, and a predictive model was constructed. The clinical parameters ALB, FIB, Na, combined alprostadil treatment and MELD, and MELD-Na scores at baseline were significantly different between the 2 groups (P <.05), while ALT, TBiL, Cre, CHE, NH3, N%, L%, PLT, INR, and PT were not significantly different (P >.05). The change rates of Na, CHE, PT, FIB, CRP, Cre, PLT, and the ratio after to before of N% were significantly different between the 2 groups (P <.05), while the change rates of ALT, TBIL, NH3, AFP, L%, and the ratio after to before of INR were not significantly different between the 2 groups (P >.05). Univariate and multivariate analyses showed that baseline ALB, Na, FIB, combined alprostadil therapy and the rate of change of Na and PLT were protective factors for disease progression, and the rate of change of PT, CRP, and the ratio after to before of N% were independent risk factors for disease progression. The novel model was LogitP = -6.051 + 4.049×ΔPT + 0.626×ΔCRP + 4.527×the ratio after to before N% and its area under the curve was 0.944 (95% confidence interval: 0.900-0.988) predicting progression of HBV-Pre.ACLF, and the best cutoff value was -0.22. The patients with a higher logitP score (> -0.22) had an increased risk for progression to ACLF (P <.05). The novel model logitP shows good predictive value for the disease progression of HBV-Pre.ACLF.

Identifying Risk Factors for Disease Progression in Developmental Dysplasia of the Hip Using a Contralateral Hip Model

Background: Developmental dysplasia of the hip (DDH) can cause pain and premature osteoarthritis. The risk factors and timing for disease progression in adolescents and young adults have not been fully defined. This study aimed to determine the prevalence of and risk factors for contralateral hip pain and surgery after periacetabular osteotomy (PAO) on a dysplastic hip. Methods: Patients undergoing unilateral PAO for DDH were followed for at least 2 years and categorized into contralateral pain and no-pain groups and contralateral surgery and no-surgery groups. Pain was defined with the modified Harris hip score. Univariate analysis tested group differences in demographics, radiographic measures, and range of motion. Kaplan-Meier survival analysis was used to assess pain development and surgery in the contralateral hip over time. Multivariable regression identified risk factors for contralateral pain and surgery. Contralateral pain and surgery predictors were secondarily assessed after categorization of the contralateral hips as dysplastic, borderline, and non-dysplastic and in subgroups based on the lateral center-edge angle (LCEA) and acetabular inclination (AI) in 5° increments. Results: One hundred and eighty-four patients were followed for a mean of 4.6 ± 1.6 years (range, 2.0 to 8.8 years), during which 51% (93) reported contralateral hip pain and 33% (60) underwent contralateral surgery. Kaplan-Meier analysis predicted 5-year survivorship of 49% with contralateral pain development as the end point and 66% with contralateral surgery as the end point. Painful hips exhibited more severe dysplasia compared with no-pain hips (LCEA = 16.5° versus 20.3°, p &lt; 0.001; AI = 13.2° versus 10.0°, p &lt; 0.001). AI was the sole predictor of pain, with every 1° increase in the AI raising the risk by 11%. Surgically treated hips also had more severe dysplasia (LCEA = 14.9° versus 20.0°, p &lt; 0.001; AI = 14.7° versus 10.2°, p &lt; 0.001) and were in younger patients (21.6 versus 24.1 years, p = 0.022). AI and a maximum alpha angle of ≥55° were predictors of contralateral surgery. Conclusions: At 5 years after hip PAO, approximately 50% of contralateral hips will have pain and approximately 35% can be expected to need surgery. More severe dysplasia, based on the LCEA and AI, increases the risk of contralateral hip pain and surgery, with AI being a predictor of both outcomes. Knowing these risks can inform patient counseling and treatment planning. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Childhood and adolescent essential thrombocythemia and prefibrotic primary myelofibrosis: insights into diagnosis, outcomes, and treatment from a large Chinese cohort.

The paucity of essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) in individuals younger than 18 years highlights several unresolved issues in diagnosis, clinical outcomes, and treatment strategies. To address these knowledge gaps, we analyzed a large bidirectional cohort consisting of childhood and adolescent ET (CAA-ET, n = 156) and pre-PMF (CAA-preMF, n = 13), as well as adult ET (n = 349). We introduced immunophenotypic abnormalities as novel clonal markers in CAA-ET and CAA-preMF, establishing a comprehensive method for clonal marker detection that integrated driver and non-driver mutations, positive endogenous erythroid colony formation, immunophenotypic abnormalities, and chromosomal aberrations. Next-generation sequencing revealed distinct mutational profiles between CAA-ET and adult ET, along with different age-related trends in the distribution of driver mutations. Venous thrombosis was more prevalent in CAA-ET, with JAK2 V617F emerging as a potential risk factor (P = 0.018). Immunophenotypic abnormalities were identified as risk factors for disease progression (P = 0.027). Significant differences between expected and actual treatment practices were identified. Compared to CAA-ET, CAA-preMF demonstrated poorer progression-free survival (P < 0.001) and faster disease progression (P = 0.019). This study provides a critical foundation for refining diagnostic, prognostic, and therapeutic approaches for CAA-ET and CAA-preMF.

Correlation of Stress and Oral Inflammatory Burden in Patients With Chronic Periodontitis in a Sample Population From Bhopal: A Randomized Clinical Study.

Introduction Chronic periodontitis is a prevalent inflammatory disease that leads to the destruction of tooth-supporting structures. Psychological stress is a potential risk factor for periodontitis, potentially exacerbating inflammation and impairing treatment outcomes. This study aims to explore the correlation between chronic stress and oral inflammatory burden, as measured by the Periodontal Inflamed Surface Area (PISA), in a sample population from Bhopal, India. Methods This randomized clinical study included 1,250 participants, divided into three groups: Group A (control, n=250), Group B (chronic periodontitis, n=500), and Group C (post-treatment chronic periodontitis, n=500). Participants underwent a comprehensive periodontal examination, including the calculation of PISA, and completed the Perceived Stress Scale-10 (PSS-10) to assess stress levels. Statistical analysis included Pearson's correlation to assess the relationship between PSS-10 scores and PISA, with comparisons among groups using analysis of variance or Kruskal-Wallis tests. Results Group B exhibited significantly higher periodontal parameters and PSS-10 scores than Group A and Group C (p<0.001 for all comparisons). Group C showed significant improvements in both periodontal parameters and PSS-10 scores following treatment (p<0.001). A positive correlation was observed between PSS-10 scores and PISA in Group B (r=0.62, p<0.001), indicating that higher perceived stress was associated with increased oral inflammation in untreated chronic periodontitis. This correlation persisted after adjusting for confounders, including age, sex, and socioeconomic status. Conclusions Chronic stress is significantly associated with increased oral inflammatory burden in patients with chronic periodontitis, suggesting that stress may act as an independent risk factor for disease progression. Periodontal therapy reduces oral inflammation and alleviates psychological distress. Integrating stress management into periodontal treatment plans may enhance patient outcomes, highlighting the importance of a holistic approach to periodontal care.

Pooled analysis of the MANTICO2 and MONET randomized controlled trials comparing drug efficacy for early treatment of COVID-19 during Omicron waves

BackgroundThe clinical effectiveness of early therapies for mild-to-moderate COVID-19, comparing antivirals and monoclonal antibodies (mAbs) during the Omicron era, has not been conclusively assessed through a post-approval comparative trial. We present a pooled analysis of two randomized clinical trials conducted during Omicron waves. Methods The MANTICO2/MONET trial is a pooled analysis of two multicentric, independent, phase-4, three-arm, superiority, randomized, open-label trials. Nonhospitalized patients with early mild-to-moderate COVID-19 (≤5 days after symptoms’ onset) and at least one risk factor for disease progression were randomized 1:1:1 to receive 500mg of intravenous sotrovimab (SOT) or 600mg of intramuscular tixagevimab/cilgavimab (TGM/CGM) or oral 5-days course of nirmatrelvir/ritonavir (NMV/r) 300/100mg BID. Primary outcome was COVID-19-related hospitalization or death within 29 days after randomization. Fisher’s exact test for pooled data and incidence of failure was reported as overall and by arm with respective 95% CI.Pairwise comparisons across the arms were conducted using unadjusted exact logistic regression. An analysis by means of a doubly robust marginal model using augmented inverse probability weighting (AIPW) was also conducted to estimate the potential outcomes (Pom) in each treatment group and their difference by the average treatment effect (ATE). Analysis of symptom persistence within 30 days after randomization was performed using a 2-level hierarchical mixed-effects logistic model with a random intercept at the patient’s level. Point estimates and 95% confidence intervals were adjusted for age and sex and calculated using ANOVA-like methods for the mixedeffects logistic model. These trials are registred with the European Clinical Trials Database, EudraCT2021-002612-31 (MANTICO2) and EudraCT2021-004188-28 (MONET) and ClinicalTrials.gov, NCT05321394 (MANTICO2) Findings Between March 2022 and February 2023, 991 patients (SOT=332, TGM/CGM =327, NMV/r=332) were enrolled in 15 Italian centersThe overall mean age was 66 years; 482 participants (48.80%) were male and 856 vaccinated with at least a primary course ( 86%). Among the 8/991 hospitalizations observed, one resulted in death. The overall estimate of failure was 0.81% (95%CI; 0.35-1.58%). The odds ratio (OR) for the primary outcome in the NMV/r arm compared to the TGM/CGM and SOT arms was 8.41 (95% CI 1.21 to infinity; p=0.015) and 2.42 (95% CI 0.19 to infinity; p=0.499), respectively. No significant difference was observed between SOT and TGM/CGM (OR 0.32; 95% CI 0.032-1.83; p=0.174). Results were similar when we applied the marginal weighted model accounting for potential residual confounding bias. There was no evidence for a difference in the prevalence of symptoms between treatment groups, except for cough, which was higher in the SOT group compared to the other two groups at the 21-day follow-up (P=0.039) and a higher prevalence of nausea at the 7-day follow-up in the NMV/r group compared to the mAbs group (p=0.036). Interpretation NMV/r was superior to TGM/CGM in reducing hospital admission or death in clinical vulnerable patients with SARS-CoV-2 infection treated within 5 days of symptoms’ onset. No significant difference in symptom prevalence over time across the arms was found. Funding: The trials were funded by the Italian Agency of Drugs (AIFA) in 2021.

Surgical management and outcomes of T4a papillary thyroid carcinoma: a single-centre study of 602 cases.

This study aimed to investigate the clinical characteristics and risk factors associated with the disease progression of T4a papillary thyroid carcinoma (PTC). In all, 602 patients (230 males; 372 females), aged 8-82 years, with T4a PTC who were admitted for initial surgery between April 2010 and September 2022 were retrospectively analysed. Tracheal invasion was observed in 271 (45.0%), oesophageal invasion in 190 (31.6%), recurrent laryngeal nerve (RLN) invasion in 516 (85.7%), and larynx invasion in 22 (3.7%) patients. The 5-year progression-free survival was 89.8%, and disease-specific survival was 96.0%, with a postoperative disease progression rate of 9.6% (54 patients) and mortality rate of 5.17% (29 patients). Disease recurrence was most likely to occur at the initial surgical site. Age ≥55 years, preoperative vocal cord paralysis, microvascular invasion, trachea invasion, and metastases to >5 cervical lymph nodes were independent risk factors for disease progression in patients with M0 stage. Male sex, preoperative vocal cord paralysis, microvascular invasion, specific pathological type, and laryngeal invasion were associated with an increased risk of disease progression for all T4a patients, while lobectomy, total thyroidectomy, tumour shaving on the RLN surface, total RLN resection, and absence of radioactive iodine therapy were not. Surgery was the primary treatment for patients with stage T4a PTC and most patients had a satisfactory prognosis. Surgeons should comprehensively evaluate each patient before deciding the surgical approach.

Predictive value of somatic and functional variables for cognitive deterioration for early-stage patients with Alzheimer's Disease: Evidence from a prospective registry on dementia.

Alzheimer's disease (AD) imposes a major burden on affected individuals, their caregivers and health-care systems alike. Though quite many risk factors for disease progression have been identified, there is a lack of prospective studies investigating the interplay and predictive value of a wide variety of patient variables associated with cognitive deterioration (defined as key feature of AD progression). Study participants were patients with probable and possible AD, that were assessed at four time points over a period of two years (T1-T4). The main results were threefold: (i) over time, significant changes were observed regarding patients' cognitive functioning, activities of daily living and caregiver load (but not depression, pain, neuropsychiatric symptoms); (ii) intercorrelations between caregiver load and patients' cognitive and functional variables were high, correlation patterns remaining rather stable across time; (iii) cognitive functioning at T4 was best predicted by patients' age, sex, atrial fibrillation and activities of daily living at T1; and (iv) across all four assessment points, cognitive functioning was best predicted by time (i.e., disease duration), age, sex, activities of daily living and depression. Overall, even in early stages of AD and during a short two-year period, functional changes were significant and tightly intertwined with caregiver load, thus stressing the need to consider caregiver load when diagnosing and treating patients with AD. A novel and clinically relevant finding is that even in early stages of AD, cognitive deterioration was best predicted by a combination of patients' demographic, somatic and functional variables.

PD-L1 and B7-H3 are Effective Prognostic Factors and Potential Therapeutic Targets for High-Risk Thyroid Cancer.

The prognosis of thyroid cancer in patients varies significantly based on different pathological types or distinct clinical situations. Investigating the expression of immune checkpoint molecules PD-L1 and B7-H3 in high-risk thyroid cancer and their correlation with clinicopathological features and prognosis will contribute to the development of novel therapeutic strategies. A retrospective sample of 202 patients with thyroid cancer who underwent surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences was collected, including 33 cases of anaplastic thyroid cancer (ATC), 21 cases of differentiated thyroid cancer (DTC) with distant metastasis (DM), 7 cases of differentiated high-grade thyroid carcinoma (DHGTC), and 109 cases of aggressive subtypes of papillary thyroid carcinoma (PTC) (including 28 cases of tall cell PTC, 31 cases of diffuse sclerosing PTC, 20 cases of solid PTC, 15 cases of columnar cell PTC, and 15 cases of hobnail PTC). In the control group, there were 32 cases of classic PTC. The differences in protein expression between PD-L1 and B7-H3 in several high-risk thyroid cancers and normal tissues and controls were compared by immunohistochemical staining, and the clinicopathological features and prognostic relevance were statistically analyzed. The expression of PD-L1 in ATC (P < 0.001), tall cell PTC (P = 0.031), and DHGTC (P = 0.003) was significantly higher than that in classic PTC. The expression of B7-H3 in ATC (P < 0.001), DTC with DM (P = 0.001), diffuse sclerosing PTC (P = 0.013), columnar cell PTC (P = 0.007), solid PTC (P < 0.001), hobnail PTC (P < 0.001), and DHGTC (P < 0.001) was significantly higher than that in classic PTC. In ATC, PD-L1 expression correlated significantly with extrathyroidal extension (ETE) (P = 0.027) and B7-H3 expression correlated significantly with male patients (P = 0.031) and lymph node metastasis (LNM) (P = 0.026). The positive expression of B7-H3 (P = 0.041) was an independent risk factor for disease progression in ATC. B7-H3 positive expression (P = 0.049), PD-L1 positive expression (P = 0.015), and tumor diameter ≥ 2cm (P = 0.038) were independent risk factors for disease progression in patients with DTC with DM. PD-L1 positive expression (P = 0.019) and tumor diameter ≥ 2cm (P = 0.018) were independent risk factors for disease progression in patients with aggressive subtypes of PTC. B7-H3 and PD-L1 are expected to be effective prognostic indicators for patients with aggressive thyroid cancer, which can help in optimization of individualized treatment strategies. Immunotherapy targeting these two molecules may provide new and complementary ideas for the treatment of high-risk/refractory thyroid cancer.

Estrogen and progesterone receptor expression: Impacts on platinum sensitivity and survival outcomes in high‐grade serous ovarian cancer

AbstractBackgroundThis study aimed to explore the impact of patient‐specific factors on the effectiveness of platinum‐based chemotherapy in ovarian cancer patients. Specifically, we investigated the relationship between estrogen receptor (ER) and progesterone receptor (PR) expression levels and platinum sensitivity, and how this influenced treatment outcomes and prognosis. We conducted a survival analysis on patients who underwent surgical treatment for serous ovarian cancer and received platinum‐based adjuvant therapies.MethodsThis study was a retrospective observational analysis of 171 patients with high‐grade serous ovarian cancer. We extracted and analyzed the patients' clinical data, focusing on platinum sensitivity concerning hormone receptor expression. We also assessed survival outcomes based on receptor expression and platinum resistance.ResultsOur findings revealed that 78.4% (n = 134) of the patients were platinum‐sensitive, while 21.6% (n = 37) were platinum‐resistant. The expression of hormone receptors showed significant associations with platinum sensitivity, particularly among ER‐positive patients (p &lt; 0.05). Age, disease stage, preoperative carbohydrate antigen 125 (CA125) levels, and residual tumor size were identified as notable factors influencing both progression‐free survival (PFS) and overall survival (OS). In terms of PFS, 88.5% of patients remained free from disease progression after one year, but this percentage dropped to 21% after five years. The average duration of PFS was 35.3 months. As for OS, 93.5% of patients were still alive after one year, but this percentage decreased to 50.5% after five years. The average survival duration was 64 months. Furthermore, platinum resistance was found to be a significant risk factor for disease progression, with a more than fivefold increase in risk (p &lt; 0.001).ConclusionOur study identified disease stage progression, ER negativity, and platinum resistance as the primary factors influencing OS. We also found that ER and PR expression played a crucial role in determining the sensitivity to platinum‐based chemotherapy in patients with serous ovarian cancer.

Profile and temporal dynamics of the feline sporotrichosis epidemic in southern Brazil: A forecasting analysis

A detailed clinical-epidemiological analysis of feline sporotrichosis was conducted, and 288 cases reported between the years 2007 and 2018 were analyzed. The studied cases primarily involved mongrel cats (240/260), males (212/282), and adults (121/200). The main objectives were to identify the risk factors, calculate the monthly incidence rates, and establish a predictive model using the seasonal autoregressive integrated moving average (SARIMA) approach. The statistical analysis revealed significant associations (p < 0.05) between prolonged lesion evolution times and factors such as respiratory signs, prior treatments, and lesion contact. Empirical treatment was identified as a significant risk factor for disease progression. Moreover, the number of cases demonstrated an increasing trend over the study period, with annual peaks noted in disease incidence. The SARIMA model proved to be an effective tool for forecasting the incidence of sporotrichosis, offering robust support for epidemiological surveillance and facilitating targeted public health interventions in endemic regions. The predictive accuracy of the developed model underscored its utility in enhancing disease monitoring and supporting proactive health measures for the effective management of sporotrichosis.

The Beijing angle closure progression study: design and methodology.

The purpose of this study is to summarize the design and methodology of a large-scale trial in northern China, the Beijing Angle Closure Progression Study (BAPS). This trial is designed to explore the 5-year incidence of primary angle-closure suspect (PACS) progressing to primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) and to determine the possible risk factors of disease progression. The BAPS is a clinic-based, multicenter, noninterventional trial conducted on a sample of urban Chinese adults. Consecutive eligible patients who meet PACS diagnostic criteria will be recruited from eight participating centers, with the trial commencing on August 4, 2022. The target sample size is set at 825 subjects, with follow up planned for a minimum period of 5 years. Baseline examination will include presenting visual acuity, best corrected visual acuity, intraocular pressure (IOP), undilated slit-lamp biomicroscopy, stereoscopic evaluation of the optic disc, visual field test, optical coherence tomography evaluation of retinal nerve fiber layer, ultrasound biomicroscopy and IOLMaster. Questionnaires will also be used to collect detailed personal history. Patients are scheduled to visit the glaucoma clinic every 12 months and may visit the emergency room in case of acute attack of angle closure. Study endpoints include acute PAC episodes, elevated IOP, peripheral anterior synechiae, glaucomatous visual field defect, or glaucomatous abnormality of optic nerve. The BAPS will provide data on the 5-year incidence of PACS progressing to PAC or PACG and determine the risk factors for disease progression. This study will also help redefine high-risk patients with PACS.

Risk Factors for Disease Progression in Glaucoma Patients With Disk Hemorrhage.

Glaucoma eyes with recurrent disk hemorrhage were associated with increased systolic blood pressure and diastolic blood pressure, and increased visit-to-visit diastolic blood pressure variability was associated with glaucoma progression. In this study, we investigated the effects of the clinical characteristics of disk hemorrhage (DH) and hemodynamic factors on glaucoma progression. This retrospective cohort study included 81 eyes with open angle glaucoma and nonrecurrent or recurrent DH. Recurrent DH was further classified according to the DH location. Visual field (VF) progression was determined using event-based analysis and Guided Progression Analysis software. The coefficient of variation (CV) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) was used to measure visit-to-visit variability. Kaplan-Meier survival analysis was used to compare the cumulative risk ratio of progression between groups. The recurrent DH group had significantly higher SBP and DBP ( P =0.014 and=0.021, respectively) and a higher proportion of VF progression ( P =0.019) than the nonrecurrent DH group. In particular, females with recurrent DH had the highest cumulative probability of VF progression ( P =0.047, log-rank test). Recurrent DH in a different quadrant was associated with the highest cumulative probability of VF progression than nonrecurrent DH ( P =0.038, log-rank test). In Cox regression analysis, higher visit-to-visit DBP variability, female gender, and recurrent DH in a different quadrant were significantly associated with glaucoma progression. In glaucomatous eyes with DH, increased visit-to-visit DBP variability was associated with glaucoma progression. Our results suggest that hemodynamic factors are involved in the recurrence of DH and progression of glaucoma.

Comparative histological and clinical differences between children and adults in IgA nephropathy

IgA nephropathy (IgAN), as an autoimmune-mediated kidney disease worldwide, is considered an important cause of end-stage renal disease in adults. The most important diagnostic method in the patients is the evaluation of the biopsy findings. To date, several studies have examined different histopathological findings in patients with IgAN with an attempt to find out the relationship between morphologic findings with outcome and disease progression. Although there have been limited reports of IgAN in children, the Oxford scoring system is currently the most widely used IgAN classification and is validated for use in children and adults. In this review, we examined the most frequently published pathological findings on IgAN with a focus on Oxford classification between adults and children and attempted to highlight the key differences. The main purpose of this study was to assess the prognosis of patients with IgAN in childhood and adulthood, with emphasis on pathological risk factors for disease progression. Our results indicated that acute glomerulonephritis in children was predominantly reported more than chronic lesions. In addition, mesangial and endocapillary lesions were more common in children than in adults. In contrast, glomerular sclerosis, tubular atrophy/interstitial fibrosis, and atherosclerotic lesions were more common in older individuals.

Long-term outcome of hepatitis delta in different regions world-wide: Results of the Hepatitis Delta International Network.

Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources. The Hepatitis Delta International Network (HDIN) registry involves researchers from all continents (Wranke, Liver International 2018). We here report long-term follow-up data of 648 hepatitis D patients recruited by 14 centres in 11 countries. Liver-related clinical endpoints were defined as hepatic decompensation (ascites, encephalopathy and variceal bleeding), liver transplantation, hepatocellular carcinoma or liver-related death. Patient data were available from all continents but Africa: 22% from Eastern Mediterranean, 32% from Eastern Europe and Central Asia, 13% from Central and Southern Europe, 14% from South Asia (mainly Pakistan) and 19% from South America (mainly Brazil). The mean follow-up was 6.4 (.6-28) years. During follow-up, 195 patients (32%) developed a liver-related clinical event after 3.5 (±3.3) years. Liver cirrhosis at baseline and a detectable HDV RNA test during follow-up were associated with a worse clinical outcome in multivariate regression analysis while patients receiving interferon alfa-based therapies developed clinical endpoints less frequently. Patients from South Asia developed endpoints earlier and had the highest mortality. The HDIN registry confirms the severity of hepatitis D and provides further evidence for HDV viraemia as a main risk factor for disease progression. Hepatitis D seems to take a particularly severe course in patients born in Pakistan. There is an urgent need to extend access to antiviral therapies and to provide appropriate education about HDV infection.

Analysis of risk factors for disease progression after salvage radiation therapy with androgen deprivation therapy in prostate cancer patients who have prostate-specific antigen persistence after radical prostatectomy.

To assess risk factors of disease progression after salvage radiation therapy (SRT) with androgen deprivation therapy (ADT) in case of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP). We analyzed 57 patients who received SRT with ADT between 2013 and 2019 due to PSA persistence after RP. The endpoint was disease progression defined by biochemical recurrence or clinical recurrence. Age, Pre-RP PSA level, Gleason score, pathologic stage, presence of pelvic lymph node dissection, surgical margins, and PSA at 6-8 weeks after RP were analyzed as predictive factors for disease progression. Kaplan-Meier method and Cox regression models were used for data analysis. At a median follow-up of 38 months (interquartile range, 26-61), 17 patients had disease progression. Pathologic T stage (pT3b vs. pT3a or lower; hazard ratio [HR] = 9.20; p = 0.035) and PSA level at 6-8 weeks after RP (≥2.04 vs. <2.04 ng/mL; HR = 5.85; p = 0.002) were predictors of disease progression. The 5-year disease progression-free survival rate was 46.7% in pT3b group as compared to 92.9 % in pT3a or lower group, and 18.4% for PSA ≥2.04 ng/mL after RP as compared to 79.2% for PSA <2.04 ng/mL. Pathological T stage (pT3b) and post RP PSA ≥2.04 ng/mL are independent risk factors of disease progression after SRT with ADT in patients with PSA persistence after RP.

Cardiac Uptake of the Adrenergic Imaging Agent meta-Iodobenzylguanidine (mIBG) Is Mediated by Organic Cation Transporter 3 (Oct3).

Heart failure (HF) is a chronic disease affecting 1%-2% of the global population.123I-labeled meta-iodobenzylguanidine (mIBG) is US Food and Drug Administration-approved for cardiac imaging and prognosis risk assessment in patients with HF. As a norepinephrine analog, mIBG is believed to be transported into adrenergic nerve terminals by the neuronal norepinephrine transporter (NET) and hence image sympathetic innervation of the myocardium. We previously showed that mIBG is an excellent substrate of organic cation transporter 3 (OCT3), an extraneuronal transporter expressed in cardiomyocytes. Here, we evaluated the in vivo impact of Oct3 on mIBG disposition and tissue distribution using Oct3 knockout mice. Oct3 +/+ and Oct3 -/- mice were administered with mIBG intravenously, and mIBG plasma pharmacokinetics and tissue exposures were determined. In Oct3 +/+ mice, mIBG exhibited extensive accumulation in multiple tissues (heart, salivary gland, liver, and adrenal gland). No difference was observed in overall plasma exposure between Oct3 +/+ and Oct3 -/- mice. Strikingly, cardiac mIBG was depleted in Oct3 -/- mice, resulting in 83% reduction in overall cardiac exposure (AUC0-24 h: 12.7 vs. 2.1 μg × h/g). mIBG tissue exposure (AUC0-24 h) was also reduced by 66%, 36%, and 31% in skeletal muscle, salivary gland, and lung, respectively, in Oct3 -/- mice. Our data demonstrated that Oct3 is the primary transporter responsible for cardiac mIBG uptake in vivo and suggested that cardiac mIBG imaging mainly measures OCT3 activity in cardiomyocytes but not NET-mediated uptake in adrenergic nerve endings. Our findings challenge the current paradigm in interpreting cardiac mIBG imaging results and suggest OCT3 as a potential genetic risk marker for HF prognosis. SIGNIFICANCE STATEMENT: 123I-labeled meta-iodobenzylguanidine is used for cardiac imaging and risk assessment in heart failure patients. Contrary to the current belief that meta-iodobenzylguanidine (mIBG) tracks cardiac sympathetic innervation due to its uptake by the neuronal norepinephrine transporter, the authors demonstrated that cardiac mIBG uptake is mediated by the extraneuronal transporter Oct3. Their findings warrant a re-evaluation of the scientific rationale behind cardiac mIBG scan and further suggest organic cation transporter 3 as a risk factor for disease progression in heart failure patients.