Systemic Disease Status Research Articles

Comprehensive comorbidity assessment for the ECOPD: a long-term multi-centre retrospective study

BackgroundExacerbation of chronic obstructive pulmonary disease (ECOPD) results in severe adverse outcomes and mortality. It is often associated with increased local and systemic inflammation. However, individual susceptibility to exacerbations remains largely unknown. Our study aimed to investigate the association between comorbidities and exacerbation outcomes.MethodsWe included patients with the primary discharge diagnosis of exacerbation for more 10 years in China. Data on all comorbidities were collected and analysed to determine the impact of the comorbidities on 1-year exacerbation readmission, length of hospital stay, and hospital cost. Univariable and multivariable logistic regression analyses were performed, and predictive models were developed.ResultsThis extensive investigation evaluated a total of 15,708 individuals from five prominent locations in China, revealing notable variations in the prevalence of comorbidities and healthcare expenses among different regions. The study shows that there is a high rate of readmission within one year, namely 15.8%. The most common conditions among readmitted patients are hypertension (38.6%), ischemic heart disease (16.9%), and diabetes mellitus (16.6%). An extensive multivariable study revealed that age, gender, and particular comorbidities such as malnutrition and hyperlipidemia are important factors that can significantly predict greater readmission rates, longer hospital stays or increased healthcare costs. The multivariable models show a moderate to good ability to predict patient outcomes, with concordance index ranging from 0.701 to 0.752. This suggests that targeted interventions in these areas could improve patient outcomes and make better use of healthcare resources.ConclusionsThe results regarding the association between severe exacerbations and systemic disease status support the integration of systematic evaluation of comorbidities into the management of exacerbations and the intensification of treatment of important comorbidities as a appropriate measure for prevention of further exacerbations. Our models also provide a novel tool for clinicians to determine the risk of the 1-year recurrence of severe ECOPD in hospitalised patients.

Impact of systemic disease on CNS disease control after stereotactic radiosurgery to breast cancer brain metastases (The SYBRA Study)

The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints [CNS failure-free survival (cFFS), overall survival (OS)] were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months). Patients were categorized into early and non-early progression (EP, NEP) groups depending on SD status before LMs. Median survivals from LM were assessed with Kaplan Meier plots, compared with Log-Rank test. EP was associated with worse median cFFS and OS vs NEP in both LM analyses (cFFS- LM1: 3.6 vs. 9.7 months, p = 0.0016; LM2: 2.3 vs. 12.5 months, p < 0.0001; OS- LM1: 3.6 vs. 24.3 months, p < 0.0001; LM2: 5.3 vs. 30.2 months, p < 0.0001). In multivariate analyses, EP was associated with shorter cFFS [LM1: Hazard Ratio (HR) with 95% confidence interval (CI) 3.16, 1.46–6.83, p = 0.0034; LM2: 5.32, 2.33–12.15, p = <0.0001] and shorter OS (LM1: HR with 95% CI 4.28, 1.98–9.12, p = 0.0002; LM2: 7.40, 3.10–17.63, p = <0.0001) vs NEP. Early systemic disease progressions after 1st SRS to brain is associated with worse cFFS and OS in patients with BCBM.

Radiosurgery to 5 or more newly diagnosed brain metastases in the systemic therapy era.

2026 Background: Stereotactic radiosurgery (SRS) is an ablative modality for focal treatment of brain metastases (BM) and is standard of care for limited BM. Suitability for SRS has historically been linked to number of BM, with up to 4 BM considered amenable to SRS. JLGK0901 revealed no difference in overall survival (OS) and similar rates of adverse events for patients with 5-10 vs. 2-4 BM. Evidence supporting for SRS for &gt;10 BM is limited. As systemic treatments have evolved to include agents with improved central nervous system (CNS) efficacy and OS, the role of SRS warrants re-evaluation. Methods: We retrospectively reviewed patients from a single institution with ≥5 BM treated with SRS with no prior history of brain radiation 2015-2022 on an IRB-approved protocol. Clinical history, including sex, histology, Karnofsky performance status (KPS), extracranial disease status and systemic regimen used before and after diagnosis of BM, was reviewed. Systemic regimens were categorized based on potential for CNS efficacy as 1) none: no evidence, 2) weak: single agent immunotherapy or known but limited data on CNS efficacy, or 3) strong: multiple agents with known CNS efficacy, single agents with strong CNS efficacy. Kaplan-Meier method was used to estimate survival with log-rank test used to evaluate differences in survival curves. Cox proportional hazards modeling was used to evaluate differences in CNS progression-free survival (CNS-PFS) and OS. Results: 558 patients (48% female) who received SRS to ≥5 BM (range 5-23) were identified. Primary histologies included: 36% non-small cell lung cancer; 22% melanoma; 14% breast; 7% renal; 5% gastrointestinal; 15% other. Median OS was 11.0 months and did not differ between patients with 5-9 (n=441) vs ≥10 BM (n=117) (median OS 11.1 vs. 10.0 months; p=0.53). Median CNS-PFS was 6.6 months and did not differ between 5-9 vs ≥ 10 BM (median CNS-PFS 6.4 vs. 7.7 p=0.86). On univariate analysis, high KPS (HR 0.96; p&lt;0.001) was associated with improved OS. Histology ( p=0.14), BM number ( p=0.53); average BM volume ( p=0.48), and systemic disease status ( p=0.17) were not associated with OS. Change of systemic therapy at time of SRS was associated with improved OS (HR 0.58; p&lt;0.001) and CNS-PFS (HR 0.63; p&lt;0.001). Amongst patients with systemic therapy change, regimens with increased CNS efficacy compared to prior therapy were associated with improved OS (HR 0.59; p&lt;0.001) and CNS-PFS (HR 0.65; p=0.002). Conclusions: In this large, retrospective analysis of patients with ≥ 5 previously untreated BM treated with SRS, we found no association between BM number and CNS-PFS or OS. Change in systemic therapy, particularly to agents with CNS efficacy, was associated with improved outcomes. While limited by biases inherent to retrospective analyses, these results suggest patients with larger number of BM (≥10) are appropriate for SRS, especially when changing to systemic therapy with CNS penetrance.

Is Tonsillolith a Protective Factor Against Covid-19 ?

Object: Tonsilloliths are the most common calcifications of the head and neck region and are also caused by inflammation of the pharyngeal lymphoid tissue. Changes that may occur in the lymphoid tissue due to tonsilloliths may affect the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This radiological study aims to investigate the potential effect of tonsilloliths on Coronavirus disease 2019 (COVID-19). Material and Methods: This study, which has a cross-sectional retrospective design, was carried out by evaluating the digital panoramic radiographs taken before the pandemic period of the patient group (n=402) who had COVID -19, who applied to the Akdeniz University Faculty of Dentistry Oral, Dental and Maxillofacial radiology clinic, and the control group (n:400) who did not have COVID -19, in terms of the presence of tonsilloliths. All Statistical analyzes were performed with SPSS version 22.0 and P &amp;lt;0.05 was considered to indicate statistical significance. The Chi-square test and Student's t-test were performed. Results: The incidence of tonsillolith was significantly lower in the patient group (29.1%) than in the control group (45%) (p &amp;lt;0.01). Both groups were similar in terms of age, gender, and systemic disease status (p = 0.1, 0.08, and 0.08, respectively). Tonsilotiths were located both uni and bilaterally (p = 0.09), but unilateral ones were more common on the right side (p = 0.04). Conclusions: The results of this study showed that high-frequency tonsilloliths may have a protective effect against COVID -19.

Investigation of the reasons for delayed presentation in proliferative diabetic retinopathy patients.

To investigate reasons for delayed presentation in patients with proliferative diabetic retinopathy (PDR). A questionnaire was designed to investigate consecutive PDR patients with delayed presentation who visited our center between January 2021 and December 2021. The questionnaire was divided into four sections: knowledge regarding diabetic retinopathy (DR), attitude toward DR treatment, difficulties adhering to follow-up plans, and medical care. The systemic disease status and severity of DR were recorded. Logistic analysis was undertaken to investigate DR treatment refusal and delay factors. A total of 157 patients were included in this study, with an average age of 50.0 ± 11.6 years. The median glycated hemoglobin level (HbA1c) was 7.8% (IQR 2.5%). Among the 157 eyes, most required vitrectomy intervention (144, 91.7%); 17 developed neovascular glaucoma (NVG), while only 13 required additional photocoagulation. Among the 36 patients with undiagnosed DM, the reason for delayed DR presentation was a lack of awareness of DM status among these patients (36 cases, 100.0%). Most of the patients with a known history of DM exhibited inadequate DR knowledge (29, 24.0%), believed their good visual acuity did not require DR screening (98, 81.0%), and had poorly controlled diabetes (113, 93.3%). Factors related to refusing DR treatment were patients with an inability to receive regular diabetes treatment in internal medicine clinics (OR 6.78, 95% CI 1.73-26.59, p = 0.006), patients who could not tolerate discomfort during ophthalmic examination and treatment (OR 15.15, 95% CI 2.70-83.33, p<0.001), and patients who did not have any retinal abnormalities detected and were not informed about the need for regular screening (OR 2.05, 95% CI 1.36-3.09, p<0.001). This study investigated the factors contributing to delayed presentation among patients with PDR. Many individuals in the delayed population were found to have undiagnosed DM. Among patients already aware of their DM status, reasons for delay included insufficient knowledge about DR, negative attitudes toward screening and treatment, and difficulties seeking medical care in real-life situations. Furthermore, there needed to be more improvements in the detection, treatment, and follow-up of DR by internal medicine practitioners and ophthalmologists.

Examining the Frequency of Systemic Diseases in Patients Referring to the Dental Surgery Department

Background: Considering the relatively high prevalence of systemic diseases, the present study investigated the frequency of systemic diseases in patients referring to the surgery department of the Zahedan Faculty of Dentistry. Methods: In this descriptive-analytical cross-sectional study, 463 patients referring to the surgery department of the Zahedan Faculty of Dentistry in 2021 - 2022 were investigated. The required information, including the type of systemic disease, age, gender, and marital status, was extracted from the patient's medical file and recorded in the designed checklist. Next, the frequency of systemic disease was compared in terms of age, gender, and marital status. Results: The frequency of systemic diseases was obtained at 27.4%. The most common systemic diseases were hypertension (8.6%), diabetes (6.6%), and anemia (4%). The frequency of systemic diseases in terms of gender and marital status did not differ significantly (P = 0.567 and P = 0.193, respectively), while it was significantly higher in those above 45 years of age compared to those younger than 45 (P &lt; 0.001). Conclusions: The prevalence of systemic diseases in patients referring to the surgery department of the Zahedan Faculty of Dentistry is relatively low compared to other studies. Hypertension, diabetes, and anemia had the highest frequency among systemic diseases.

Pachymeningeal disease: a systematic review and metanalysis.

Pachymeningeal disease (PMD) is a newly recognized pattern of brain metastasis (BrM) failure that specifically occurs following surgery with adjuvant stereotactic radiosurgery (SRS) and has unique prognostic implications relative to leptomeningeal disease (LMD). Here, we report its prevalence, prognostic implications, and associated risk factors. A literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses on PUBMED and Cochrane from January 2000 to June 2023. We identified 12 studies that included a total of 3992 BrM patients, 659 (16.5%) of whom developed meningeal disease (MD) following surgery plus adjuvant SRS, including either PMD or LMD. The mean prevalence of MD across studies was 20.9% (7.9-38.0%), with PMD accounting for 54.6% of this prevalence and LMD comprising the remaining 45.4%. Mean of the median overall survivals following diagnosis of PMD and LMD was 10.6 months and 3.7 months p = 0.007, respectively, a significant difference. Only 2 risk factors for PMD were reported in ≥ 2 studies and also identified as statistically significant per our meta-analysis: infratentorial location and controlled systemic disease status. While PMD has a superior prognosis to LMD, it is nevertheless a critical oncologic event associated with significant mortality and remains poorly recognized. PMD is predominantly observed in patients with controlled systemic disease status and infratentorial location. Future treatment strategies should focus on reducing surgical seeding and sterilizing surgical cavities.

P13.06.A RADIOMIC FEATURES FOR RISK-STRATIFICATION IN PATIENTS WITH BRAIN METASTASES

Abstract BACKGROUND Recently, non-invasive characterization of brain tumors on MRI has emerged as a promising field of research. The identification of quantitative imaging biomarkers, also known as radiomics, may complement molecular characterization and thereby improve clinical management of neuro-oncologic patients. In this study we aimed to identify imaging predictors with improved performance over clinical parameters in order to stratify patients with brain metastases into high and low risk groups for overall survival (OS). MATERIAL AND METHODS 422 patients (allocated in a 3:1 ratio to a discovery [n=317] and test [n= 105] set) with first diagnosis of brain metastases from different primary tumors from two neuro-oncologic centers were included. In each patient, eight clinical features (age, gender, KPS, systemic disease status, presence of extracranial metastases, number of cerebral metastases, primary tumor and available individual prognostic molecular status eg HER2, BRAF,⋯) were gathered and a total of 321 radiomic MRI features (including shape, first-order and higher-order features) from cerebral MRI (contrast T1-weighted and apparent diffusion coefficient maps) were extracted. Radiomic and clinical features of patients in the discovery set were subjected to different machine learning models in order to classify patients into low- and high-risk groups for OS. By performing a comprehensive grid search the best machine learning model according to the macro-evaluated score and accuracy was identified and evaluated on the testing set. In addition, a subgroup analysis, based on the primary tumor entity was done and confusion matrices were calculated in order to evaluate final predictions. RESULTS With an extra trees classifier including all clinical and 30 radiomic features, we were able to stratify patients into a high- and low-risk group for OS (test set: macro-evaluated = 0.60, accuracy = 0.67). The best performing model was a gradient boosting model only including clinical features (test set: macro-evaluated = 0.62, accuracy = 0.72), while the radiomic features alone led to the poorest results (test set: macro-evaluated = 0.52, accuracy = 0.63). Interestingly, in the subgroup of melanoma patients, the predictive power of radiomic features outperformed the clinical and the combined (radiomics and clinical) features. With a prediction solely based on radiomic features, 80% and 67% of patients were correctly classified into the low- and the high-risk group for OS, respectively. CONCLUSION In conclusion, we found that in the entire study population of patients with brain metastases radiomic features did not allow for a better prediction of the clinical outcome compared to the clinical parameters alone. However, in the subgroup of melanoma patients the predictive power of radiomic features alone was superior compared to clinical features or all features combined.

Identification of risk factors associated with leptomeningeal disease after resection of brain metastases.

Resection of brain metastases (BMs) may be associated with increased risk of leptomeningeal disease (LMD). This study examined rates and predictors of LMD, including imaging subtypes, in patients who underwent resection of a BM followed by postoperative radiation. A retrospective, single-center study was conducted examining overall LMD, classic LMD (cLMD), and nodular LMD (nLMD) risk. Logistic regression, Cox proportional hazards, and random forest analyses were performed to identify risk factors associated with LMD. Of the 217 patients in the cohort, 47 (21.7%) developed postoperative LMD, with 19 cases (8.8%) of cLMD and 28 cases (12.9%) of nLMD. Six-, 12-, and 24-month LMD-free survival rates were 92.3%, 85.6%, and 71.4%, respectively. Patients with cLMD had worse survival outcomes from the date of LMD diagnosis compared with nLMD (median 2.4 vs 6.9 months, p = 0.02, log-rank test). Cox proportional hazards analysis identified cerebellar/insular/occipital location (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.73-6.11, p = 0.0003), absence of extracranial disease (HR 2.49, 95% CI 1.27-4.88, p = 0.008), and ventricle contact (HR 2.82, 95% CI 1.5-5.3, p = 0.001) to be associated with postoperative LMD. A predictive model using random forest analysis with an area under the receiver operating characteristic curve of 0.87 in a test cohort identified tumor location, systemic disease status, and tumor volume as the most important factors associated with LMD. Tumor location, absence of extracranial disease at the time of surgery, ventricle contact, and increased tumor volume were associated with LMD. Further work is needed to determine whether escalating therapies in patients at risk of LMD prevents disease dissemination.

Outcome for Children and Young Adults With T-Cell ALL and Induction Failure in Contemporary Trials.

Historically, patients with T-cell acute lymphoblastic leukemia (T-ALL) who fail to achieve remission at the end of induction (EOI) have had poor long-term survival. The goal of this study was to examine the efficacy of contemporary therapy, including allogeneic hematopoietic stem cell transplantation (HSCT) in first remission (CR1). Induction failure (IF) was defined as the persistence of at least 5% bone marrow (BM) lymphoblasts and/or extramedullary disease after 4-6 weeks of induction chemotherapy. Disease features and clinical outcomes were reported in 325 of 6,167 (5%) patients age 21 years and younger treated in 14 cooperative study groups between 2000 and 2018. With a median follow-up period of 6.4 years (range, 0.3-17.9 years), the 10-year overall survival (OS) was 54.7% (SE = 2.9), which is significantly higher than the 27.6% (SE = 2.9) observed in the historical cohort from 1985 to 2000. There was no significant impact of sex, age, white blood cell count, central nervous system disease status, T-cell maturity, or BM disease burden at EOI on OS. Postinduction complete remission (CR) was achieved in 93% of patients with 10-year OS of 59.6% (SE = 3.1%) and disease-free survival (DFS) of 56.3% (SE = 3.1%). Among the patients who achieved CR, 72% underwent HSCT and their 10-year DFS (with a 190-day landmark) was significantly better than nontransplanted patients (63.8% [SE = 3.6] v 45.5% [SE = 7.1]; P = .005), with OS of 66.2% (SE = 3.6) versus 50.8% (SE = 6.8); P = .10, respectively. Outcomes for patients age 21 years and younger with T-ALL and IF have improved in the contemporary treatment era with a DFS benefit among those undergoing HSCT in CR1. However, outcomes still lag considerably behind those who achieve remission at EOI, warranting investigation of new treatment approaches.

Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases

Preoperative stereotactic radiosurgery (SRS) has been demonstrated as a feasible alternative to postoperative SRS for resectable brain metastases (BMs) with potential benefits in adverse radiation effects (AREs) and meningeal disease (MD). However, mature large-cohort multicenter data are lacking. To evaluate preoperative SRS outcomes and prognostic factors from a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases-PROPS-BM). This multicenter cohort study included patients with BMs from solid cancers, of which at least 1 lesion received preoperative SRS and a planned resection, from 8 institutions. Radiosurgery to synchronous intact BMs was allowed. Exclusion criteria included prior or planned whole-brain radiotherapy and no cranial imaging follow-up. Patients were treated between 2005 and 2021, with most treated between 2017 and 2021. Preoperative SRS to a median dose to 15 Gy in 1 fraction or 24 Gy in 3 fractions delivered at a median (IQR) of 2 (1-4) days before resection. The primary end points were cavity local recurrence (LR), MD, ARE, overall survival (OS), and multivariable analysis of prognostic factors associated with these outcomes. The study cohort included 404 patients (214 women [53%]; median [IQR] age, 60.6 [54.0-69.6] years) with 416 resected index lesions. The 2-year cavity LR rate was 13.7%. Systemic disease status, extent of resection, SRS fractionation, type of surgery (piecemeal vs en bloc), and primary tumor type were associated with cavity LR risk. The 2-year MD rate was 5.8%, with extent of resection, primary tumor type, and posterior fossa location being associated with MD risk. The 2-year any-grade ARE rate was 7.4%, with target margin expansion greater than 1 mm and melanoma primary being associated with ARE risk. Median OS was 17.2 months (95% CI, 14.1-21.3 months), with systemic disease status, extent of resection, and primary tumor type being the strongest prognostic factors associated with OS. In this cohort study, the rates of cavity LR, ARE, and MD after preoperative SRS were found to be notably low. Several tumor and treatment factors were identified that are associated with risk of cavity LR, ARE, MD, and OS after treatment with preoperative SRS. A phase 3 randomized clinical trial of preoperative vs postoperative SRS (NRG BN012) has began enrolling (NCT05438212).

SURG-05. SUPERVISED MACHINE LEARNING IDENTIFIES RISK FACTORS ASSOCIATED WITH LEPTOMENINGEAL DISEASE AFTER SURGICAL RESECTION OF BRAIN METASTASES

Abstract INTRODUCTION Predictors of postoperative leptomeningeal disease (LMD) after resection of brain metastases (BMs) are not well defined. OBJECTIVE This study examined rates and predictors of LMD, including subtypes, in patients who underwent resection of a BM followed by postoperative radiation.Method: A retrospective, single-center study was conducted examining overall LMD, classical LMD (cLMD), and nodular LMD (nLMD) risk. Logistic regression and a Cox proportional hazards analyses were performed to identify risk factors associated with LMD. Random forest models were constructed to predict LMD and differentiate cLMD versus nLMD. Accuracy and the area under the receiver operating characteristic curve (AUROC) were calculated to evaluate the models.Result: Of the 217 patients in the cohort, 47 (21.7%) developed postoperative LMD with 19(8.8%) cLMD cases and 28(12.9%) nLMD cases . Six-, 12-, and 24-month LMD-free survival rates were 92.3%, 85.6%, and 71.4%, respectively. Patients with cLMD had worse survival outcomes from LMD diagnosis compared to nLMD (2.4 vs 6.9 mo, Log-rank p=0.02), and treatment of LMD was associated with improved survival for both cLMD and nLMD subtypes. Multivariate Cox hazard analysis identified cerebellar/insular/occipital location (HR 3.25, 95% CI 1.73-6.11, p=0.0003), absence of extracranial disease (HR 2.49, 95% CI 1.27-4.88, p=0.008), and ventricle contact (HR 2.82, 95% CI 1.5-5.3, p=0.001) to be associated with postoperative LMD. A predictive model using random forest analysis with an AUROC of 0.87 in a test cohort identified tumor location, systemic disease status, and tumor volume as the most important factors associated with LMD. Both regression analysis and random forest analysis identified postoperative systemic therapy exposure as the main factor differentiating cLMD from nLMD development. CONCLUSION Tumor location, absence of extracranial disease at the time of surgery, contact with a ventricle, and increased tumor volume are associated with LMD. Classical LMD is associated with worse prognosis compared to nLMD.

CHOROIDAL AMYLOID DEPOSITION: A Multicenter Study of Amyloid Lesions Identified in Late Indocyanine Green Angiography.

To characterize choroidal amyloid angiopathy (CAA) using late-phase indocyanine green angiography (ICGA). This was a multicenter retrospective observational case series on patients with transthyretin (ATTR) and AL amyloidosis who underwent ICGA. The timing of hyperfluorescence and longitudinal changes were analyzed. Thirty-two patients (27 with ATTR and 5 with AL) with mean age of 58.9 ± 17.4 years were included. Hyperfluorescent spots in the very late phases of ICGA, corresponding to CAA, were observed in 49 of 55 eyes (89%). The median time to maximal staining was 672 (95% confidence interval, 644-752) seconds, which was significantly later than the initial staining (503 [95% confidence interval, 447-521], P < 0.0001; Wilcoxon signed rank test). In seven patients with ATTR amyloidosis who underwent follow-up of ICGA, the CAA was stable in two patients and improved in five patients during treatment. However, 3 patients (43%) had worsening vitreous opacities in both eyes, and 4 patients (57%) developed secondary open-angle glaucoma. Most patients with amyloidosis were found to have CAA on ICGA. Up to 12.5 minutes is required for maximal ICG staining. Choroidal amyloid angiopathy improved in most patients with systemic treatment and may serve as a marker of systemic disease status.

Surgery for brain metastases: radiooncology scores predict survival-score index for radiosurgery, graded prognostic assessment, recursive partitioning analysis

BackgroundRadiooncological scores are used to stratify patients for radiation therapy. We assessed their ability to predict overall survival (OS) in patients undergoing surgery for metastatic brain disease.MethodsWe performed a post-hoc single-center analysis of 175 patients, prospectively enrolled in the MetastaSys study data. Score index of radiosurgery (SIR), graded prognostic assessment (GPA), and recursive partitioning analysis (RPA) were assessed. All scores consider age, systemic disease, and performance status prior to surgery. Furthermore, GPA and SIR include the number of intracranial lesions while SIR additionally requires metastatic lesion volume. Predictive values for case fatality at 1 year after surgery were compared among scoring systems.ResultsAll scores produced accurate reflections on OS after surgery (p ≤ 0.003). Median survival was 21–24 weeks in patients scored in the unfavorable cohorts, respectively. In cohorts with favorable scores, median survival ranged from 42 to 60 weeks. Favorable SIR was associated with a hazard ratio (HR) of 0.44 [0.29, 0.66] for death within 1 year. For GPA, the HR amounted to 0.44 [0.25, 0.75], while RPA had a HR of 0.30 [0.14, 0.63]. Overall test performance was highest for the SIR.ConclusionsAll scores proved useful in predicting OS. Considering our data, we recommend using the SIR for preoperative prognostic evaluation and counseling.

Analysis of vanishing endometrial cancer by pathological types.

We asked why endometrial cancer sometimes vanishes. A total of 454 patients diagnosed with endometrioid-type endometrial cancer (EC) (via endometrial sampling) and treated in our clinic over the past 5 years were enrolled. The patients were divided into two groups: vanishing and residual, depending on whether a tumor was detected in the postoperative hysterectomy specimen. Patient age, numbers of pregnancies and deliveries, menopausal status, systemic disease status, hemogram parameters, International Federation of Gynecology and Obstetrics (FIGO) grade, and invasion status (evident on magnetic resonance imaging [MRI]) were compared between the groups. ECs vanished in 42 (9.25%) patients. The vanishing rates were 19.7% (37/187) in FIGO grade 1 patients, 2.1% (5/238) in grade 2 patients, and 0% (0/29) in grade 3 patients. The average age was lower in the vanishing than the residual group, but the premenopausal status and grade 1 tumor rates were higher (both p < 0.001). An absence of invasion (as revealed by MRI) was more common in the vanishing group (p < 0.001). No recurrence developed in the vanishing group, but recurrences were noted in 3.3% (14/412) of the residual group. There were no significant between-group differences in any of the numbers of pregnancies or births, systemic disease status, or hemogram parameters (all p > 0.05). Vanishing EC is more likely in premenopausal women with endometrioid grade 1 EC (as revealed by endometrial biopsy) who lack myometrial invasion on MRI.

Co-Infection of Oral Candida albicans and Porphyromonas gingivalis Is Associated with Active Periodontitis in Middle-Aged and Older Japanese People

Background and Objectives: Candida albicans can be detected in subgingival sites of patients with periodontitis. However, the association between oral Candida albicans and periodontitis has not been fully elucidated in Japanese adults. The aim of this study is to clarify the relationship between oral Candida albicans infection/co-infection of oral C. albicans and Porphyromonas gingivalis and periodontitis among middle-aged and older Japanese people. Materials and Methods: Eighty-six patients (mean age 70.4 years) who visited the Hiroshima University Hospital from April to September 2021 were investigated in this study. Oral swab samples were collected from the tongue surface. C. albicans and P. gingivalis DNA was detected by real-time PCR using specific DNA primer sets. C. albicans-positive participants were classified into two groups according to the presence or absence of intron insertion of C. albicans DNA by PCR analysis. Results: C. albicans was detected in 22 (25.6%) of the 86 patients. Patients in their 80s recorded a higher C. albicans-positive rate (35.3%) compared with other participants. However, there was no significant association between the C. albicans positivity rate and clinical parameters such as sex, age, systemic disease, denture use, or oral health status. Of the 22 C. albicans-positive participants, 10 participants (45.5%) had C. albicans with intron insertion; 70% of participants who had C. albicans with intron insertion exhibited ≥6 mm probing depth. C. albicans/P. gingivalis co-infection was found in 12 patients (14%). Importantly, binomial logistic regression analysis revealed that C. albicans/P. gingivalis co-infection was significantly associated with ≥6 mm periodontal pockets with bleeding on probing (p = 0.02). Conclusions: Co-infection of C. albicans and P. gingivalis is involved in active periodontitis in middle-aged and older people.

Comprehensive summary and retrospective evaluation of prognostic scores for patients with newly diagnosed brain metastases treated with upfront radiosurgery in a modern patient collective

BackgroundNumerous prognostic scores (PS) for patients with brain metastases (BM) have been developed. Recently, PS based on laboratory parameters were introduced to better predict overall survival (OS). A comprehensive comparison of the wide range of scores in a modern patient collective is still missing. Materials and methodsTwelve PS considering clinical parameters only at the time of BM diagnosis were calculated for 470 patients receiving upfront SRS between January 2014 and March 2020. In a subcohort of 310 patients where a full laboratory dataset was available five additional prognostic scores were compared. Restricted mean survival time (RMST), partial likelihood and c-index were calculated as metrics for performance evaluation. Univariable and multivariable analysis were used to identify prognostic factors for OS. ResultsThe median OS of the whole cohort was 15.8 months (95% C.I.: 13.4–20.1). All prognostic scores performed well in separating patients into different prognostic groups. RPA achieved the highest c-index, whereas GGS achieved highest partial likelihood with evaluation in the total cohort. With incorporation of the laboratory scores the recently suggested EC-GPA achieved highest c-index and highest partial likelihood. A prognostic score solely based on the assessment of performance status achieved considerable high performance as either 3- or 4-tiered score. Multivariable analysis revealed performance status, systemic disease status and laboratory parameters to be significantly associated with OS among variates included in prognostic scores. ConclusionAlthough recent PS incorporating laboratory parameters show convincing performance in predicting overall survival, older scores relying on clinical parameters only are still valid and appealing as they are easier to calculate, and as overall performance is almost equal. Moreover, a score just based on performance status is not significantly inferior and should at least be assessed for informed decision making.

Determination of estrogen receptor alpha gene (ESR1) polymorphism and its relation to systemic lupus erythematosus disease status

BackgroundSystemic lupus erythematosus (SLE) is a chronic inflammatory disease with variable clinical manifestations that can affect various organs and tissues. Estrogen is an important element that performs a vital role in the pathology of SLE. It acts on target cells through binding to estrogen receptors (ERs). This study aimed to assess the effect of ER alpha gene polymorphism on SLE disease activity and clinical manifestations. This study included 30 SLE female patients and 20 healthy subjects as controls. ERα gene (pvull and xbal) polymorphisms were genotyped using the real-time polymerase chain reaction (RT-PCR) and correlated with clinical and laboratory manifestations of SLE as well as the activity and severity scores.ResultsRegarding ERα (rs1 2234693 Pvull) polymorphism, the TC and CC genotypes were mainly associated with SLE patients, with a high frequency of the mutant C allele. The TT genotype was found mainly in the control group. Concerning rs2 9340799 Xbal polymorphisms, the AG, AA, and GG genotypes frequencies were not significantly different between patient and controls. The TC/AA, CC/GG, and CC/GG genotypes were the most prevalent combinations among SLE patients, while the later combination is completely absent from the control group. There was a significant statistical association with the AA genotype with the neurological disorders and/or hematological affection in SLE patients. The TC genotype was more related to serositis, leucopenia and pyuria, while the AA polymorphism was associated only with leucopenia.ConclusionsWe conclude that the study offers a clue to the associations of ERα gene polymorphisms in SLE disease, and the combinations relevant to certain clinical manifestations. Estrogen level itself does not affect SLE susceptibility or activity but the mutations in its receptors are the main pathogenic factor.

EFFICACY OF MYCOPHENOLATE MOFETIL VERSUS CYCLOPHOSPHAMIDE IN THE TREATMENT OF LUPUS NEPHRITIS

Objective: Despite the prevalence of SLE, lupus nephritis (LN) is the primary cause of morbidity and mortality. This study objective was to assess the efficacy and safety of the induction treatment with mycophenolate mofetil (MMF) and cyclophosphamide (CYC). Methods: This was a prospective observational study enrolled 100 LN patients who were treated with MMF and cyclophosphamide. In this study, 6 male and 44 female patients were treated with MMF and 3 male and 47 female patients were treated with cyclophosphamide. To estimate drug efficacy, patients were evaluated for 24-h urinary protein excretion estimation, serum creatinine, protein-creatinine ratio (PCR), Proteinuria, Serum complement C3, Serum complement C4, and Serum albumin. The primary end point was a prespecified decrease in urine PCR and stabilization of serum creatinine. Secondary end points were complete renal remission, systemic disease status and safety. Results: The results indicated a potential small advantage of MMF over CYC although the results were not significant. Serum creatinine, 24-h urine protein, and serum albumin were also similar between the MMF and CYC groups after induction therapy. Leukopenia was significantly reduced in MMF treated patients. Both groups suffered from upper gastrointestinal symptoms, but the MMF group’s symptoms were mild and self-limited. MMF therapy was effective in reducing proteinuria and boosting serum complement levels. Conclusion: MMF and CYC were not significantly different in remission induction therapies for LN. Clinical improvement was seen in most patients in both treatment groups.

Survival Outcomes and Symptom Benefit From Palliative Radiotherapy in Breast Cancer Patients With Leptomeningeal Disease

The benefit of radiotherapy (RT) in poor-prognosis patients with leptomeningeal disease (LMD) is not well characterized. This study assessed the overall survival (OS) and clinical improvement of a largely symptomatic cohort of breast cancer patients with LMD, to identify patient subsets most likely to benefit from palliative RT.Patients with breast cancer and classic radiographic LMD (36% cytology-confirmed) treated with palliative whole brain and/or partial spine RT between 2000-2020 at a single academic institution were included in this retrospective analysis. OS was calculated from date of LMD diagnosis using the Kaplan-Meier method, and differences in subgroups were determined using the log-rank test. Multivariate Cox proportional hazards models adjusting for estrogen receptor (ER), progesterone receptor (PR), HER2, ECOG performance status (ECOG), and systemic disease status assessed factors associated with OS. Domain-specific and any symptom improvement were ascertained by chart review of patient- and physician-report, and a multivariate logistic regression model developed incorporating ER/PR status, HER2 status, ECOG and steroid use to identify factors associated with symptom benefit.Among 64 patients of median age 50 years (IQR 31-69), the radiographic distribution of LMD was in the brain (58%), spine (22%), or both (20%). A total of 63% had concurrent brain metastases, and 57% of patients had ER+ and/or PR+ tumors, 22% HER2+, and 38% triple-negative disease. Among 92% of symptomatic patients whose primary symptom domains were cranial nerve deficit (34%), sensory/motor deficits due to intracranial disease (25%) sensory/motor deficits due to spine disease (27%), and headaches/nausea (14%), 42% had > 1 reported symptom domain. Two-thirds of patients were on steroids prior to RT, and only 13% of patients received intrathecal therapy. Following a median dose of 30 Gy in 10 fractions, symptom improvement in any domain was noted in 59% of patients with symptoms pre-RT, with similar improvement rate across domains (12%, 15%, 19%, 14%, respectively); 21% of patients had improvement in > 1 symptom domain. Overall survival was only 2.1 months (95% CI 1.8-3.3) in the triple-negative subgroup, and higher among patients with HER2+ disease (5.2 months, 95% CI 3.8-NR, P = 0.003). On multivariate analysis, ER+ (HR 0.4, 95% CI 0.2-0.8, P = 0.009) and HER2+ (HR 0.4, 95% CI 0.2-0.9, P = 0.018) disease were associated with improved OS. Hormone receptor positivity was independently associated with symptom improvement following RT (OR 3.5, 95% CI 1.2-11, P = 0.029).Even in this poor-prognosis cohort of breast cancer patients with LMD, palliative RT yields symptomatic improvement, and may especially be of benefit among better-prognosis patients with hormone receptor-positive or HER2-positive disease.J. Takayesu: None. E. Sapir: Research Grant; LipoMedix, BioProtect. Consultant; AstraZeneca, MSD, Belong.Life. J. Xie: None. Y. Sun: None. A. Morikawa: Institutional research; Novartis, Lilly, Takeda, Eisai/H3b, Pfizer/National Comprehensive Cancer Network. L. Junck: Advisory Board; Orbus Therapeutics. D. Leung: None. Y. Umemura: None. J. Heth: None. W. Al-Holou: None. D.R. Wahl: Research Grant; Agios Inc, Innocrin Inc, American Cancer Society, NIH. Stock Options; Lycera Inc. Advisory Board Member; Agios Inc. T.S. Lawrence: None. C. Mayo: None. J.A. Hayman: Research Grant; Blue Cross Blue Shield of Michigan. M.M. Kim: Research Grant; Blue Earth Diagnostics.