Immune-Related Adverse Event Likelihood Score Identifies "Pure" IRAEs Strongly Associated With Outcome in a Phase I-II Trial Population.

BACKGROUND: Immune-related adverse events (IRAE) pose a significant diagnostic and therapeutic challenge in patients treated with immune-oncology (IO) drugs. IRAEs have been suggested to correlate with better outcome, but studies are conflicting. Estimating the true incidence of IRAEs is particularly difficult in the early phase I/II trial setting. A key issue is the lack of IRAE diagnostic criteria, necessary to discriminate "pure" IRAEs from other treatment-related adverse events not sustained by an autoimmune process. METHODS: In patients treated with immune-oncology (IO) drugs in phases I-II trials at our institute, we identified high confidence (HC) or low confidence (LC) IRAEs by clinical consensus. We empirically developed an IRAE likelihood score (ILS) based on commonly available clinical data. Correlation with outcome was explored by multivariate Cox analysis. To mitigate immortal time-bias, analyses were conducted (1) at 2-month landmark and (2) modeling IRAEs as time-dependent covariate. RESULTS: Among 202 IO-treated patients, 29.2% developed >1 treatment-related adverse events (TRAE). Based on ILS >5, we classified patients in no IRAE (n = 143), HC IRAE (n = 24), or LC IRAE (n = 35). hazard ratios (HR) for HC were significantly lower than LC patients (HR for PFS ranging 0.24-0.44, for OS 0.18-0.23, all P < .01). CONCLUSION: ILS provides a simple system to identify bona fide IRAEs, pruning for other treatment-related events likely due to different pathophysiology. Applying stringent criteria leads to lower and more reliable estimates of IRAE incidence and identifies events with significant impact on survival.

Development of a Novel Prediction Tool for Response to First-Line Treatments of Monosymptomatic Nocturnal Enuresis: A Randomized, Controlled, International, Multicenter Study (DRYCHILD).

PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. MATERIALS AND METHODS: A randomized, controlled, international, multicenter study was conducted in 324 treatment-naïve children (6-14 years old) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment, and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated. RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (risk ratio = 1.21 [1.02-1.45], P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (risk ratio = 1.46 [1.14-1.87], P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (receiver operating characteristic curve 0.85). CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improves response to first-line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response. CLINICAL TRIAL REGISTRATION NO.: NCT03389412.

Comprehensive geriatric assessment predicts radiation-induced acute toxicity in prostate cancer patients.

PURPOSE: The purpose of the present prospective study was to evaluate the significance of geriatric conditions measured by a comprehensive geriatric assessment (GA) for the prediction of the risk of high-grade acute radiation-induced toxicity. METHODS: A total of 314 prostate cancer patients (age ≥ 65 years) undergoing definitive radiotherapy at a tertiary academic center were included. Prior to treatment, patients underwent a GA. High-grade toxicity was defined as acute toxicity grade ≥ 2 according to standard RTOG/EORTC criteria. To analyze the predictive value of the GA, univariable and multivariable logistic regression models were applied. RESULTS: A total of 40 patients (12.7%) developed acute toxicity grade ≥ 2; high grade genitourinary was found in 37 patients (11.8%) and rectal toxicity in 8 patients (2.5%), respectively. Multivariable analysis revealed a significant association of comorbidities with overall toxicity grade ≥ 2 (odds ratio [OR] 2.633, 95% confidence interval [CI] 1.260-5.502; p = 0.010) as well as with high-grade genitourinary and rectal toxicity (OR 2.169, 95%CI1.017-4.625; p = 0.045 and OR 7.220, 95%CI 1.227-42.473; p = 0.029, respectively). Furthermore, the Activities of Daily Living score (OR 0.054, 95%CI 0.004-0.651; p = 0.022), social status (OR 0.159, 95%CI 0.028-0.891; p = 0.036), and polypharmacy (OR 4.618, 95%CI 1.045-20.405; p = 0.044) were identified as independent predictors of rectal toxicity grade ≥ 2. CONCLUSION: Geriatric conditions seem to be predictive of the development of high-grade radiation-induced toxicity in prostate cancer patients treated with definitive radiotherapy.

Predicting Trifluridine/Tipiracil Treatment Outcomes in Refractory Metastatic Colorectal Cancer Patients: A Multicenter Exploratory Analysis.

INTRODUCTION: There are no recommended biomarkers to identify patients with refractory metastatic colorectal cancer (mCRC) who would benefit the most from trifluridine/tipiracil (TTP). The exploratory analysis of the RECOURSE trial revealed that patients with low tumor burden and indolent disease derive greater benefit in terms of both progression-free survival (PFS) and overall survival (OS). Nevertheless, the final answer on the TTP real impact on the well-being of patients with late-stage mCRC will come from real-world data. METHODS: The aim of this retrospective exploratory study was to investigate the effectiveness of TTP in mCRC with regard to the duration of standard treatment and other influencing variables. The study included 260 patients from the three largest Croatian oncology centers who began treatment with TTP in the third or fourth line between 2018 and 2020. RESULTS: The median OS and PFS for the entire cohort were 6.53 and 2.50 months, respectively. Patients with more aggressive disease, defined as those whose time to progression on the first two lines of standard therapy was less than 18 months, had significantly shorter PFS (2.40 vs. 2.57 months, hazard ratio [HR] 1.34, 95% confidence interval [CI]: 1.03-1.84). There was also a tendency toward shorter OS (6.10 vs. 6.30 months, HR 1.32, 95% CI: 0.99-1.78) but without statistical significance. Patients with ECOG PS 0, without liver metastases, and with RAS mutation had both longer OS and PFS. No influence was detected from other variables including age, sex, primary tumor location, and tumor burden. CONCLUSION: With regard to the results of the previously conducted trials, the study concludes that indolent disease, good general condition, and absence of liver metastases are positive predictive factors for TTP treatment.

Predictive Factors of Apparent Treatment Resistant Hypertension Among Patients With Hypertension Identified Using Electronic Health Records.

BACKGROUND: Early identification of a patient with resistant hypertension (RH) enables quickly intensified treatment, short-interval follow-up, or perhaps case management to bring his or her blood pressure under control and reduce the risk of complications. OBJECTIVE: To identify predictors of RH among individuals with newly diagnosed hypertension (HTN), while comparing different prediction models and techniques for managing missing covariates using electronic health records data. DESIGN: Risk prediction study in a retrospective cohort. PARTICIPANTS: Adult patients with incident HTN treated in any of the primary care clinics of one health system between April 2013 and December 2016. MAIN MEASURES: Predicted risk of RH at the time of HTN identification and candidate predictors for variable selection in future model development. KEY RESULTS: Among 26,953 individuals with incident HTN, 613 (2.3%) met criteria for RH after 4.7 months (interquartile range, 1.2-11.3). Variables selected by the least absolute shrinkage and selection operator (LASSO), included baseline systolic blood pressure (SBP) and its missing indicator (a dummy variable created if baseline SBP is absent), use of antihypertensive medication at the time of cohort entry, body mass index, and atherosclerosis risk. The random forest technique achieved the highest area under the curve (AUC) of 0.893 (95% CI, 0.881-0.904) and the best calibration with a calibration slope of 1.01. Complete case analysis is not a valuable option (AUC = 0.625). CONCLUSIONS: Machine learning techniques and traditional logistic regression exhibited comparable levels of predictive performance after handling the missingness. We suggest that the variables identified by this study may be good candidates for clinical prediction models to alert clinicians to the need for short-interval follow up and more intensive early therapy for HTN.

Optimizing ketogenic diet therapy for childhood epilepsy: Identifying key factors for seizure control and psychomotor enhancement.

OBJECTIVE: To identify key factors influencing the therapeutic efficacy of the ketogenic diet (KD) for children with drug-resistant epilepsy and elucidate their interconnected relationships to optimize clinical practice. METHODS: Participants were selected from children receiving KD treatment at West Second University Hospital of Sichuan University from September 2015 to October 2023. Clinical factors pre-KD and post-KD (at the third month) were analyzed systematically using an analytical framework. Descriptive analyses, univariate analyses, and multivariate regression analyses were performed for the entire cohort and subgroups of genetic and non-genetic (i.e., structural and unknown) etiologies. Thereby, the most significant predictors were identified for each relevant dependent variable. Path analysis diagrams were used for visual representation. RESULTS: Of 156 patients, genetic etiology was prevalent (38.5%). In the genetic subgroup, channelopathies predicted lower baseline seizure frequency and increased chance of seizure freedom with KD. Frequent seizures and complex history of anti-seizure medications (ASMs) predicted severe baseline psychomotor abnormalities. Younger age at KD initiation benefited psychomotor improvement. In the non-genetic subgroup, lower baseline seizure frequency increased the likelihood of seizure freedom post-KD. Concurrent use of multiple ASMs helped achieve ≥50% seizure reduction. Boys were more likely to experience psychomotor improvement. A significant correlation was found between ≥50% seizure reduction and psychomotor improvement in both subgroups. Delayed KD initiation (longer epilepsy duration at KD start) was related to a greater number of ASMs used, infrequent seizures, and older age at epilepsy onset. In addition, patients with channelopathies had delayed initiation of KD. SIGNIFICANCE: Children with genetic epilepsy display more pronounced characteristics of epileptic encephalopathy. Early KD intervention is crucial for channelopathies, notably SCN1A variants. For other drug-resistant epilepsy cases, KD alongside diverse ASMs may improve seizure control and developmental outcomes. However, the patient population benefiting most from early KD tends to start the treatment later, urging a re-evaluation of KD decision-making paradigms.

Palliative care for in-patient malignant glioma patients in Germany.

OBJECTIVE: Malignant gliomas impose a significant symptomatic burden on patients and their families. Current guidelines recommend palliative care for patients with advanced tumors within eight weeks of diagnosis, emphasizing early integration for malignant glioma cases. However, the utilization rate of palliative care for these patients in Germany remains unquantified. This study investigates the proportion of malignant glioma patients who either died in a hospital or were transferred to hospice care from 2019 to 2022, and the prevalence of in-patient specialized palliative care interventions. METHODS: In this cross-sectional, retrospective study, we analyzed data from the Institute for the Hospital Remuneration System (InEK GmbH, Siegburg, Germany), covering 2019 to 2022. We included patients with a primary or secondary diagnosis of C71 (malignant glioma) in our analysis. To refine our dataset, we identified cases with dual-coded primary and secondary diagnoses and excluded these to avoid duplication in our final tally. The data extraction process involved detailed scrutiny of hospital records to ascertain the frequency of hospital deaths, hospice transfers, and the provision of complex or specialized palliative care for patients with C71-coded diagnoses. Descriptive statistics and inferential analyses were employed to evaluate the trends and significance of the findings. RESULTS: From 2019 to 2022, of the 101,192 hospital cases involving malignant glioma patients, 6,129 (6% of all cases) resulted in in-hospital mortality, while 2,798 (2.8%) led to hospice transfers. Among these, 10,592 cases (10.5% of total) involved the administration of complex or specialized palliative medical care. This provision rate remained unchanged throughout the COVID-19 pandemic. Notably, significantly lower frequencies of complex or specialized palliative care implementation were observed in patients below 65 years (p < 0.0001) and in male patients (padjusted = 0.016). In cases of in-hospital mortality due to malignant gliomas, 2,479 out of 6,129 cases (40.4%) received specialized palliative care. CONCLUSION: Despite the poor prognosis and complex symptomatology associated with malignant gliomas, only a small proportion of affected patients received advanced palliative care. Specifically, only about 10% of hospitalized patients with malignant gliomas, and approximately 40% of those who succumb to the disease in hospital settings, were afforded complex or specialized palliative care. This discrepancy underscores an urgent need to expand palliative care access for this patient demographic. Additionally, it highlights the importance of further research to identify and address the barriers preventing wider implementation of palliative care in this context.

Clinical characteristics and predictive factors of delayed diagnosis in patients with sellar germ cell tumors.

PURPOSE: To investigate the clinical characteristics and predictive factors associated with delayed diagnosis in patients with sellar germ cell tumors (GCTs), aiming for early diagnosis. METHODS: A total of 345 patients with sellar GCTs were retrospectively collected. Patients were classified into a delayed diagnosis group (> 6 months from onset to diagnosis) and a non-delayed diagnosis group (≤ 6 months). We compared general characteristics, clinical symptoms, diagnostic methods, treatment strategies, tumor prognosis, and pituitary function between the two groups. Predictive factors for delayed diagnosis were explored using multivariate logistic regression analysis. RESULTS: 225 patients (65.2%) experienced delayed diagnosis. Although there was no association between delayed diagnosis and survival rates or tumor recurrence rates, the delayed diagnosis group had a higher incidence of central diabetes insipidus, central adrenal insufficiency, central hypothyroidism, central hypogonadism, and growth hormone deficiency. Moreover, polyuria/polydipsia (OR 5.46; 95% CI 2.33-12.81), slow growth (OR 5.86; 95% CI 2.61-13.14), amenorrhea (OR 6.82; 95% CI 2.68-17.37), and germinoma (OR 4.99; 95% CI 1.08-3.61) were associated with a higher risk of delayed diagnosis, while older age of onset (OR 0.88; 95% CI 0.84-0.94) and nausea/vomiting (OR 0.31; 95% CI 0.15-0.63) contributed to earlier diagnosis. CONCLUSION: In patients with sellar GCTs, delayed diagnosis is common and linked to increased pituitary dysfunction. The initial symptoms of slow growth, polyuria/polydipsia, and amenorrhea, as well as germinoma with negative tumor markers, predict the possibility of a delayed diagnosis. Early diagnosis is crucial to minimize the impact of sellar GCTs on pituitary function.

Epidemiology and risk factors for staphylococcal urinary tract infections in the Moroccan Casablanca area.

PURPOSE: This study aimed to ascertain the prevalence and risk factors for developing staphylococcal urinary tract infections (UTIs) in the Casablanca area of Morocco. METHODS: In Casablanca, Morocco, a retrospective evaluation of 772 UTIs patients was conducted between January 2020 and December 2022. The research included two groups of patients: those with staphylococcal UTIs and those without. Sex, age, chronic illnesses, antibiotic exposure, urinary catheterization, urological surgery, and UTIs history were the risk variables assessed. We employed a logistic regression model to identify the characteristics that were predictive of staphylococcal UTIs. RESULTS: Eight staphylococcal species were responsible for 16.84% of UTIs in 772 non-repeating individuals. Patients infected with S. saprophyticus (35.38%) were the most common, followed by those infected with S. epidermidis (24.61%), S. aureus (13.85%), and S. hemolyticus (10.78%). Multivariate logistic regression analysis revealed that male sex (95% CI: 0.261-0.563), immunosuppression and immunosuppressive treatments (95% CI: 0.0068-0.64), chronic diseases (95% CI: 0.407-0.965), previous UTIs (95% CI: 0.031-0.228), frequency of urination more than 8 times a day (95% CI:1.04-3.29), frequency of urination once or twice a day (95% CI: 1.05-2.39), and urinary catheterization (95% CI: 0.02-0.22) were the most likely predictors of staphylococcal UTIs. In addition, a larger proportion of patients with staphylococcal UTIs were made aware of the risk factors associated with staphylococcal UTIs (52.31%, χ2 = 4.82, = 0.014). CONCLUSIONS: This is the first global study to evaluate the predictive factors for acquiring UTIs caused by staphylococci. Monitoring these factors will enable medical authorities to devise effective strategies for managing UTIs and combating antibiotic resistance.

Prediction of 5-year survival in soft tissue leiomyosarcoma using a machine learning model algorithm.

BACKGROUND AND OBJECTIVES: Leiomyosarcoma (LMS) is associated with one of the poorest overall survivals among soft tissue sarcomas. We sought to develop and externally validate a model for 5-year survival prediction in patients with appendicular or truncal LMS using machine learning algorithms. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used for development and internal validation of the models; external validation was assessed using our institutional database. Five machine learning algorithms were developed and then tested on our institutional database. Area under the receiver operating characteristic curve (AUC) and Brier score were used to assess model performance. RESULTS: A total of 2209 patients from the SEER database and 81 patients from our tertiary institution were included. All models had excellent calibration with AUC 0.84-0.85 and Brier score 0.15-0.16. After assessing the performance indicators according to the TRIPOD model, we found that the Elastic-Net Penalized Logistic Regression outperformed other models. The AUCs of the institutional data were 0.83 (imputed) and 0.85 (complete-case analysis) with a Brier score of 0.16. CONCLUSION: Our study successfully developed five machine learning algorithms to assess 5-year survival in patients with LMS. The Elastic-Net Penalized Logistic Regression retained performance upon external validation with an AUC of 0.85 and Brier score of 0.15.

Predictive factors for recurrent acute appendicitis after conservative treatment.

INTRODUCTION: Conservative treatment of acute appendicitis is gaining popularity, and identifying patients with a higher risk of recurrence is becoming increasingly important. Previous studies have suggested that older age, male sex, diabetes, appendicolith and abscess formation may be contributing factors, however, results from the adult population are inconsistent. AIM: This study aims to identify predictive factors for recurrent appendicitis after conservative treatment. METHODS: This retrospective study included patients with conservatively treated acute appendicitis at Skåne University Hospital, Sweden during 2012-2019. Information on patient demographics at index admission and follow-up data were retrieved from medical charts and radiologic images. Uni -and multivariable logistic regression analysis were performed using Stata Statistical Software. RESULTS: In total, 379 patients with conservatively treated acute appendicitis were identified, of which 78 (20.6%) had recurrence. All patients were followed-up for a minimum of 41 months after the first diagnosis of acute appendicitis unless appendectomy after successful conservative treatment or death occurred during follow-up. The median time to recurrence was 6.5 (1-17.8) months. After multivariable logistic regression analysis, external appendix diameter >10 mm [OR 2.4 (CI 1.37-4.21), p = .002] and intra-abdominal abscess [OR 2.05 (CI 1.18-3.56), p = .011] on computed tomography were significant independent risk factors for recurrent appendicitis. Appendicolith was not associated with an increased risk of recurrence. CONCLUSION: This study suggests abscess formation and appendix distension of >10 mm to be potential risk factors for recurrent acute appendicitis after initial successful conservative treatment.

Association of diabetes and white blood cell count with stroke in patients with carotid artery dissection.

BACKGROUND: Carotid artery dissection is an important cause of stroke. However, the predictors of ischemic stroke in patients with carotid artery dissection are controversial. The study aimed to analyze the predictors of ischemic stroke in patients with carotid artery dissection through retrospective medical records. METHODS: Data of discharged patients diagnosed with carotid artery dissection during 2019-2023 were retrospectively collected. Based on the occurrence of ischemic stroke, the patients were divided into the ischemic stroke or non-ischemic stroke groups. Based on the results of univariate analyses, variables with an associated P value < 0.05 were introduced into the multivariable logistic regression analysis. . RESULTS: A total of 165 patients were included in the study, with an average age of 55.00 (48.00, 66.00) years, including 86 patients with internal carotid artery dissection and 79 patients with vertebral artery dissection. Ischemic stroke occurred in 69 patients with carotid artery dissection. Multivariate logistic regression analysis indicated that diabetes (odds ratio [OR]: 3.144, 95% confidence interval [CI]: 1.552-6.508, P<0.002) and high white blood cells count (OR: 1.157, 95% CI: 1.02-1.327,P = 0.028) were related to the incidence of ischemic stroke in patients with carotid artery dissection. CONCLUSION: Ischemic stroke caused by carotid artery dissection causes severe damage to the nervous system. This study found that diabetes and high white blood cells count were associated with the incidence of ischemic stroke in patients with carotid artery dissection. Therefore, monitoring and controlling blood glucose levels and infections is essential in patients with carotid artery dissection to reduce the incidence of stroke.

Comparison between MRI-negative and positive results and the predictors for a poor prognosis in patients with idiopathic acute transverse myelitis.

BACKGROUND: Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported. OBJECTIVES: The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis. METHODS: We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models. RESULTS: Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result. CONCLUSIONS: Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.

Initial Holter Electrocardiogram Index to Predict the Burden of Subsequent Persistent Premature Ventricular Complex in Childhood.

BACKGROUND: Asymptomatic premature ventricular complex (PVC) in childhood often disappears over time. However, predictive factors for persistent PVC are unknown. We examined predictive factors for persistent PVCs on initial Holter electrocardiogram (ECG) in pediatric patients with asymptomatic PVC.Methods and Results: The initial Holter ECG findings of untreated PVC patients (n=216) between 2010 and 2021 were examined. Multivariable analysis was performed to clarify predictive factors for subsequent persistent PVC burden for each index (age, sex, PVC burden, PVC origin, minimum and maximum mean RR intervals [RRmin and RRmax, respectively]) of the 3 heartbeats of baseline sinus rhythm immediately before the PVC. The median age at initial Holter ECG was 11.6 years (range 5.8-18.8 years), the PVC burden was 5.22% (range 0.01-44.21%), RRmin was 660 ms, RRmax was 936 ms, RRrange (=RRmax-RRmin) was 273 ms, and 15 (7%) PVC runs were identified. The median follow-up period was 5.1 years (range 0.8-9.4 years), and the final Holter PVC burden was 3.99% (range 0-36.38%). In multivariate analysis, RRrange was the only independent risk factor for predicting a final Holter PVC burden >10%, with an area under the curve of 0.920 using an RRrange of 600 ms as the cut-off value. CONCLUSIONS: A wide RRrange at the initial Holter ECG may be a predictive indicator for persistent PVC in childhood.

Risk factors for significant histological changes in both HBeAg positive and negative treatment-naive chronic hepatitis B with persistently normal alanine aminotransferase level.

BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a serious health issue, and determining the optimal time for antiviral therapy is challenging. We aimed to assess liver histological changes in patients with HBeAg-positive chronic hepatitis B (CHB) and those with HBeAg-negative CHB who had persistently normal alanine aminotransferase and to determine the association between significant liver injury and various clinical parameters. METHODS: We retrospectively included, in this study, 339 treatment-naïve patients with chronic HBV infections who had persistently normal alanine aminotransferase and underwent liver biopsy from 2013 to 2023. Histologic assessment was based on the Metavir scoring system to evaluate the association between clinical characteristics and the severity of liver inflammation and fibrosis. RESULTS: Among the included participants, 138 were HBeAg-positive and 201 were HBeAg-negative. Lower hepatitis B surface antigen (HBsAg) (P = 0.003) and higher aspartate aminotransferase (AST) (P = 0.002) levels were associated with significant necroinflammation, whereas increasing age (P = 0.004) and lower HBV DNA (P < 0.001) levels were associated with significant fibrosis in HBeAg-positive patients with normal ALT levels. Higher HBV-DNA (P = 0.001) and AST levels(P < 0.001) were associated with significant necroinflammation, and higher AST(P < 0.001) levels were associated with significant fibrosis in HBeAg-negative patients. CONCLUSIONS: A substantial proportion of patients with HBV infection who had normal ALT presented significant liver injury. HBsAg and AST were independent predictive factors for evaluating inflammation, while HBV DNA load and age were independent predictive factors for evaluating fibrosis in the HBeAg-positive group. HBV DNA load and AST were independent predictive factors for evaluating inflammation, while AST were independent predictive factors for evaluating fibrosis in the HBeAg-negative group.

The incidence and predictive factors of secondary epilepsy in patients with supratentorial brain metastases (st-BMs) after stereotactic radiosurgery: A multicenter retrospective study.

OBJECTIVE: To evaluate the incidence and the independent risk factors of SRS-related epilepsy in patients with supratentorial brain metastases (st-BMs), providing evidences for prevention or reduction secondary epilepsy after SRS. METHODS: Patients with st-BMs from four gamma knife centers who developed secondary epilepsy after SRS were retrospectively studied between January 1, 2017 and June 31, 2023. The incidence and clinical characteristics of the patients with secondary epilepsy were analyzed. The predictive role of baseline clinical-demographic variables was evaluated according to univariate and multivariate logistic regression model. The impact of secondary epilepsy on patients' OS was evaluated as well by log-rank test. RESULTS: 11.3 % (126/1120) of the patients with totally 158 st-BMs experienced secondary epilepsy after SRS in median 21 days. 61.9 % (78/126) of the patients experienced simple partial seizures. 91.3 % (115/126) patients achieved good seizure control after received 1-2 kinds of AEDs for median 90 days, while 7.1 % (9/126) of the patients suffered from refractory epilepsy. Patients had higher risk of secondary epilepsy if the tumor located in cortex and/or hippocampus, peri-tumor edema larger than 20.3 cm3 before SRS, had epilepsy history, and failed to receive bevacizumab prior to SRS. There was no difference in the OS of patients who experience secondary epilepsy or not after SRS. CONCLUSIONS: The incidence of SRS-related secondary epilepsy is 11.3 % in patients with st-BMs in this retrospective study. The risk of secondary epilepsy is higher in patients with st-BM located in cortex and/or hippocampus area, peri-tumor edema larger than 20.3 cm3 before SRS, and epilepsy history. Bevacizumab is suggested prior to SRS therapy, as it could be used for the control of peri-tumor edema and SRS-related damage, hence reduce the risk of secondary epilepsy. However, whether or not patients suffered from secondary epilepsy after SRS does not affect their OS.

Response to first-line pembrolizumab in metastatic KRAS-mutated non-small-cell lung cancer.

Aims: This retrospective study aims to identify a possible predictive role of KRAS mutations in non-small-cell lung cancer in response to first-line pembrolizumab, either as monotherapy or combined with chemotherapy. Methods: Patients received pembrolizumab alone (n = 213) or associated with chemotherapy (n = 81). Results: A mutation in the KRAS gene was detected in 27% of patients. In patients on pembrolizumab alone, median progression-free survival in KRAS-mutated cases was longer than in wild-type cases (11.3 vs 4.4 months; p = 0.019), whereas median overall survival did not reach statistical significance (22.1 vs 12.5 months; p = 0.119). Patients receiving chemo-immunotherapy with KRAS-positive tumors had a similar progression-free survival (9.7 vs 7.3 months; p = 0.435); overall survival data were immature. Conclusion: This study suggests a correlation between KRAS status and response to pembrolizumab.

Analysis of trajectory changes and predictive factors of sense of coherence in patients after colorectal cancer surgery.

OBJECTIVE: To investigate the trajectories and potential categories of changes in the sense of coherence (SOC) in patients after colorectal cancer surgery and to analyze predictive factors. METHODS: From January to July 2023, 175 patients with colorectal cancer treated at a tertiary Grade A oncology hospital in Jiangsu Province were selected as the study subjects. Prior to surgery, SOC-13 scale, Patient-Generated Subjective Global Assessment (PG-SGA), Brief Illness Perception Questionnaire (BIPQ), and Social Support Rating Scale (SSRS) were used to survey the patients. SOC levels were measured multiple times at 1 week, 1 month, and 3 months post-surgery. Growth Mixture Modeling (GMM) was applied to fit the trajectory changes of SOC in patients after colorectal cancer surgery. Multinomial logistic regression was used to analyze the predictive factors of SOC trajectory changes. RESULTS: The SOC scores of patients at points T1-T4 were (65.27 ± 9.20), (63.65 ± 10.41), (63.85 ± 11.84), and (61.56 ± 12.65), respectively. Multinomial logistic regression results indicated that gender, employment status, disease stage, household monthly income, intestinal stoma, nutritional status, illness perception, and social support were predictors of SOC trajectory changes (P < 0.05). CONCLUSION: There is heterogeneity in the trajectory changes of SOC in patients after colorectal cancer surgery. Healthcare professionals should implement early precision interventions based on the patterns of changes and predictive factors in each trajectory category.

Discharge Outcomes of Hospitalized Patients with New Onset Decompensated Cirrhosis.

INTRODUCTION: There are a lack of data describing outcomes and follow-up after hospital discharge for patients with newly diagnosed cirrhosis with complication on index admission. This study examines factors that influence outcomes such as readmission, follow-up, and mortality for patients with newly diagnosed cirrhosis. METHODS: We conducted a single-center retrospective chart review study of 230 patients with newly diagnosed cirrhosis from January 1st, 2020 through December 31st, 2021. We obtained demographics, clinical diagnoses, admission, and discharge MELD-Na, disposition, mortality, appointment requests rate, appointment show rate, and readmission. RESULTS: The primary complications on admission were GI bleed (27%), ascites (25.7%), and hepatic encephalopathy (HE) (10.4%). Overall, the median length of stay (LOS) was 6 days, and the readmission rate was 27%. Out of 230 patients, 25 (10.9%) patients died while hospitalized while another 43 (18.6%) died after initial discharge within the two-year study period. Although there was a significant reduction of the MELD-Na from admission to discharge (p < 0.05), admission MELD-Na did not correlate with LOS and discharge MELD-Na did not predict readmission. Patients with HE had the highest median LOS, while patients with ascites had the highest readmission rate. The median time to an appointment was 32 days. When comparing discharge destinations, most patients were discharged to home (63%), to facilities (13.9%), or expired (10.9%). The average appointment show rate was 38.5%, although 70% of patients had appointment requests. Readmission rate and mortality did not differ based on appointment requests. No significant differences in outcomes were observed based on race, sex, or insurance status. CONCLUSION: New diagnosis of decompensated was found to have high mortality and high readmission rates. Higher MELD-Na score was seen in patients who died within 30 days. Routine appointment requests did not significantly improve readmission, mortality, increase appointment show rate, or decrease time to appointment. A comprehensive and specialized hepatology-specific program may have great benefits after cirrhotic decompensation, especially for those with newly diagnosed cirrhosis.

Examining associations between disordered eating and harmful substance use in a nationally representative sample of US veterans.

OBJECTIVE: The association between eating disorders (EDs) and harmful substance use (substance use that causes psychosocial impairment) is well recognized in the literature, and military veterans may be at heightened risk for both issues due to deployment-related stressors. However, little is known about which ED-related symptoms are associated with harmful substance use in veterans, and whether gender plays a differential role in this relationship. Our aims were to: (1) examine gender differences in ED-related symptoms; and (2) examine whether ED-related symptoms differentially predict harmful substance use in US veteran men and women who had recently separated from service. METHOD: This study was based on a nationally representative four-wave longitudinal sample of post-9/11 veterans (N = 835; 61.2% female). Longitudinal mixed modeling was used to test whether specific ED-related behaviors at baseline predicted harmful substance use at follow-ups. RESULTS: We replicated gendered patterns of ED-related symptoms observed in civilian populations, wherein men had higher weight-and-body-related concerns (including excessive exercise and muscle building) and negative attitude toward obesity, and women had higher bulimic and restricting symptoms. For women, alcohol, drug, and marijuana problems were predicted by higher bulimic symptoms, whereas for men, these problems were predicted by higher restricting symptoms. CONCLUSION: Gender played a differential role in the relationship between EDs and harmful substance use. Bulimic symptoms were the most robust predictor for harmful substance use among veteran women, whereas restricting was the most robust predictor for harmful substance use among veteran men. PUBLIC SIGNIFICANCE: The current study found that veteran women had higher bulimic symptoms (characterized by binge eating and purging) and restricting than veteran men. In women, bulimic symptoms predicted future harmful use of alcohol, marijuana, and other drugs. In contrast, veteran men had higher weight-and-body-related concerns (characterized by excessive exercise and muscle building) than veteran women. In men, restricting symptoms predicted future harmful use of alcohol, marijuana, and other drugs.