Pretreatment Factors Research Articles

SURG-23. THE INFLUENCE OF PRE-OPERATIVE VARIABLES ON SURVIVAL OF PATIENTS WITH GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma (GBM) is both the most common and most aggressive brain tumor in adults. Despite treatment advances, prognosis remains poor and is influenced by numerous factors. METHODS Patients treated at our institution for glioblastoma were reviewed to identify pre-treatment factors that could increase survival time. 183 treated for high-grade GBM between 2017 and 2021 with complete follow-up data were included. Overall (OS) and progression-free survival (PFS) were calculated with Kaplan-Meier analysis. Cox regression analysis identified the influence of several pre-treatment factors (age, Karnofsky performance status (KPS), radiographic distribution of tumor, and MGMT methylation status) on survival time. RESULTS Average age was 64.9 years. At presentation, 69.9% of patients had KPS > 80. Multifocal tumors occurred in 24.6% of patients, involving an average of 2 distinct regions (either multifocal or unifocal lesions). MGMT methylation was confirmed in 17.5% of patients. Recurrence occurred in 46.4% of patients. Median OS was 21.6 (14.3 – 28.9) months and PFS was 13.4 (10.6 – 16.1) months. MGMT methylation was associated with significantly longer median OS (36.9 vs. 17.0 months, p = 0.012) and PFS (20.0 vs. 10.3 months, p = 0.002) compared to those without. Cox regression confirmed MGMT methylation to be significantly associated with longer PFS (HR -0.883, p = 0.004) and OS (HR -0.785, p = 0.014). Age (HR 0.03, p = 0.003) and KPS > 80 (HR -0.7, p = 0.006) significantly impacted OS, but not PFS. Tumor extent did not impact survival. CONCLUSIONS We found that multifocal tumor, greater number of involved regions. and older age were associated with shorter OS, while MGMT methylation was associated with longer OS. Similar correlations were found for PFS. In upcoming trials, these factors may need to be controlled for between groups in order to accurately determine the effect of new treatments.

Countertransference in the treatment of patients with personality disorders: A longitudinal study

ABSTRACT Objective This study examines how therapist emotional response/countertransference (CT) develops during treatment for patients with personality disorders (PDs) and how pre-treatment patient factors (severity of personality pathology, PD category, level of symptom distress) predict CT responses. Secondly, we explored associations between patient clinical outcome and CT. Method A longitudinal, observational study including 1956 patients with personality pathology treated at psychotherapy units within specialist mental health services. Therapists’ emotional response was repeatedly assessed by the Feeling Word Checklist—Brief Version (FWC-BV) with three subscales—Inadequate, Confident, and Idealized. Results Levels of Inadequate CT were lowest and stable over time while Confident and Idealized increased over time. Greater severity of personality pathology and borderline PD predicted higher initial Inadequate, lower initial Confident and decreasing Inadequate over time. Antisocial PD predicted decreasing Confident. Number of PD criteria had higher impact on therapist CT than level of symptom distress. Clinical improvement was associated with decreasing Inadequate. Conclusion Therapists reported predominantly Confident CT when working with PD patients. More severe personality pathology, and borderline PD, specifically, predicted more negative CT initially, but the negative CT decreased over time. Patients who did not improve were associated with increasing Inadequate.

Predictors of therapeutic response to peginterferon α‑2a and nucleos(t)ide analog combination therapy for HBeAg‑negative chronic hepatitis B: 1‑year follow‑up after treatment.

Chronic hepatitis B (CHB) is a major global health concern. Guidelines for the management of hepatitis B virus (HBV) indicate that the loss of hepatitis B surface antigen (HBsAg) is a key endpoint of interest. The present study aimed to examine long-term changes in HBsAg levels in HBV-DNA-negative, hepatitis B e-antigen (HBeAg)-negative patients treated with peginterferon (Peg-IFN) α-2a and nucleos(t)ide analog (NA), and to examine the conditions that make them susceptible to HBsAg decline. A total of 17 patients with CHB treated with NA and Peg-IFN were observed for 96 weeks (48 weeks of Peg-IFN therapy and 48 weeks of post-treatment follow-up). In this study, responders were defined as those with a 50% or greater decrease in HBsAg levels from baseline at week 96. Beginning at week 16 of Peg-IFN therapy, there was a significant difference in the decrease in HBsAg levels from baseline between the responders and non-responders. In responders, HBsAg levels tended to be >60% lower 16 weeks after Peg-IFN initiation than before initiation. Age at the start of NA use and the duration of NA use before Peg-IFN treatment initiation were significant pretreatment factors associated with HBsAg response. In conclusion, Peg-IFN was revealed to be more effective in HBeAg-negative patients with CHB who started NA at a young age and have been on long-term treatment, particularly if the HBsAg levels decreased to less than 60% of the starting level at week 16 after starting Peg-IFN treatment.

Single Cell RNA Sequencing of Sequential Samples before and after BCMA-Directed CAR-T Reveal Features Associated with Non-Durable Response, Exhausted T-Cells and Decreased Expression of Genes Encoding Key Surface Targets in Particular in Patients with Extramedullary Disease

Introduction Single cell sequencing confers a unique opportunity to study the complex interplay between the malignant plasma cells (PCs) and the host tumor microenvironment (TME) within the bone marrow niche. Pre-treatment factors associated with the achievement of durable responses from anti-B-cell maturation antigen (BCMA) directed CART cell therapy remain poorly understood. Herein, we performed a longitudinal single cell analysis to identify factors associated with response, or therapeutic failure, to FDA approved BCMA-directed CART cell therapy. Methods We performed single-cell RNA sequencing (scRNA-seq) to comprehensively characterize both the cellular and molecular properties of malignant plasma cells and TME. Separated CD138+ and CD138- components were universally encapsulated within hours of pre-CART baseline (BL) and day 90 post treatment with commercial CAR-T using 10x Genomics. Libraries were sequenced separately on an Illumina NovaSeq 6000 instrument. Cell Ranger pipelines with default parameters were used to trim reads, align, count unique molecular identifiers, and call cells. Downstream processing was carried out using Seurat. Batch effects were corrected using canonical correlation analysis (CCA) integration. After quality control for feature counts and mitochondrial gene expression, there were a total of 110,923 single cells, including 48,150 plasma cells (PC) and 62,773 TME cells. In addition, we integrated these data with an internal repository of bulk RNA sequencing (RNAseq) (N=844 CD138+ MM cells) to evaluate co-regulation of genes (Renatino-Canevarolo et al, ASH 2022). Patients were split into two broad groups, durable (DR) vs non-durable response (NDR) based on PFS cutoff of 9 months. Given its negative impact on outcomes, we also examined differences between those with or without extra-medullary disease (EMD). Results Median PFS for the total cohort of N=13 at the time of data cutoff was 332 days (range 279-569) for DR and 28 days (12-197) for NDR. Malignant cells were identified based on inferred copy number alterations and comparison to benign plasma cell controls from sequenced healthy donors. Single-cell expression profiles of plasma cells are primarily clustered by patient, whereas expression of non-plasma cells largely clustered by cell types. In DR, expression of BL malignant PCs revealed enriched expression of genes encoding several known surface markers, including FCRL5, CD38, TACI and BCMA, and genes associated with a more plasma-cell-like phenotype, such as XBP1, whereas EEF2 and CD48/SLAMF2 were increased in BL PCs from NDR.Pathway analysis of DR vs NDR revealed upregulated activity genes involved in the interleukin-6 pathway, interferon γ and oxidative phosphorylation (padj <0.1). In contrast, MYC pathways and unfolded protein response genes (padj < 0.1) were significantly upregulated in NDR ( Figure 1). Analysis of the BL TME illustrated fewer CD4 naïve, CD4 effector memory (EM), T effector memory RA-positive (TEMRA) cells and higher CD8 central memory (CM) cells in NDR vs DR patients. Exhaustion signatures were higher among BL CD4 and CD8 cells pre-CART in NDR relative to DR, and in D90 samples this was also more pronounced among CD4 cells in NDR vs DR samples. Comparing D90 to BL, DR patients had fewer Tregs, increased numbers of trafficking monocytes and more proliferating CD8 T-cells. Finally, looking at patients with EMD, differences in surface target gene expression were noted with decreased expression of BCMA, TACI, FCRL5, and CD38 observed, although CD44 and Ly9 expression appeared equivalent or enriched in those with known EMD (Figure 2). Interrogation of bulk RNAseq revealed that several of these genes, including BCMA, PRDM1/Blimp-1, XBP1, CD138 are co-regulated in a common geneset. This geneset was significantly downregulated in patients with NDR vs DR. Conclusion These data highlight the pre-treatment features of both tumor and T-cell that can pre-dispose real-world patients with RRMM to early relapse after anti-BCMA CAR-T, notably pre-existing T-cell exhaustion, and the presence of highly proliferative plasma cells with underlying resistance mechanisms, including downregulation of several known immunotherapy targets, especially in those with co-existing EMD. Ciara L Freeman, Xiaohong Zhao & Mark B Meads contributed equally

Development and Validation of Oral Health-Related Quality of Life Scale for Patients Undergoing Endodontic Treatment (OHQE) for Irreversible Pulpitis

An oral health-related quality of life measure specific to patients undergoing endodontic treatment has not been developed. This study aimed to validate the oral health-related quality of life scale for patients undergoing endodontic treatment (OHQE) for irreversible pulpitis, comprised of 42 questions. Sixty-two patients with irreversible pulpitis, comprising 23 (37.1%) males and 39 (62.9%) females, were enrolled between August 2022 and February 2023. Data were collected at three time points: pretreatment, post-treatment, and at the second week post-treatment. Factor analysis revealed physical, psychological, and expectations as subscales of OHQE. Cronbach’s alpha coefficients ranged from 0.87 to 0.95 for each subscale. Each subscale of the General Oral Health Assessment Index (GOHAI) was moderately correlated with the OHQE subscales. Good–poor analysis revealed a significant difference between the high-scoring and low-scoring groups for each OHQE subscale. The intraclass correlation coefficients of the OHQE subscales ranged from 0.89 to 0.95. Multivariate linear regression analysis revealed a significant correlation between the pretreatment and post-treatment psychological factors (p < 0.05). Thus, OHQE will help researchers and policymakers understand the impact of oral health on the quality of life of patients with irreversible pulpitis undergoing endodontic treatment. OHQE could contribute to the appropriate planning, treatment decisions, and management of dental treatment.

Analysis of Artificial Intelligence-Based Automated Phenotyping of Coronary Artery Disease Diagnoses for Patients who Received Radiotherapy for Thoracic Malignancies.

Coronary artery disease (CAD) is a critical risk factor and toxicity endpoint in thoracic radiation oncology. The recent advent of artificial intelligence (AI) algorithms - specifically natural language processing (NLP) - allows for automated extraction of this data from electronic health records (EHR) more efficiently and at scale. We report on the application and performance characteristics of an EHR-based automated phenotyping tool to a cohort of lung cancer patients receiving radiation therapy (RT). We applied to this radiation oncology use-case an AI-based disease phenotyping tool developed by other researchers for phenotyping CAD from the EHR. The CAD model was trained on 191,187 patients with at least one ICD code and validated with 158 gold-standard patients (Sensitivity: 73%, Specificity: 93%, PPV: 90%). NLP disease definitions were determined by UMLS and were employed with ICD codes through PheNorm classification method to create the phenotype algorithm (Yue et al., J Am Med Inform Assoc. 2018 Jan 1; 25(1):54-60). We applied the CAD phenotyping tool to two independent cohorts of RT treated lung cancer patients: 1) an annotated set of 677 patients who received RT from 1998 to 2014 and were studied in prior cardiac toxicity research; 2) an independent set of 209 patients who received RT from 1998 to 2018 and were annotated separately. Only 7.7% of the AI training population had a CAD diagnosis code, compared to 32.5% and 65.0% in the 677 patient and 209 patient cohorts, respectively. Validation of the AI predicted CAD is shown in the table below. Performance on the 209 patient cohort best matched the AI training set. The 677-patient cohort differed from the 209-patient cohort in that its CAD definition included patients with radiographic coronary artery calcifications, which accounted for the difference in cohort sensitivities, F-scores, and NPVs. The AI calculated CAD was somewhat accurate in detecting whether a patient had CAD and was very accurate in confirming no CAD. The differences in sensitivity and NPV reflect differences in defining CAD, but this study demonstrates the potential for automated AI-phenotyping to detect pre-treatment risk factors and cardiac toxicity events from the EHR.

Factors associated with diagnostic and pre-treatment intervals among breast cancer patients attending care at the Uganda Cancer Institute: A cross-sectional study.

Most breast cancer (BC) patients in Uganda are diagnosed with advanced-stage disease and experience poor outcomes. This study examined the diagnostic and pre-treatment intervals and factors associated with these intervals among BC patients attending care at the Uganda Cancer Institute (UCI). This was a cross-sectional, facility-based study. Data were collected using structured questionnaire administered by trained research assistants and analyzed using STATA version 14.0. Modified Poisson regressions models were used to determine the strength of associations between independent variables and diagnostic and pre-treatment intervals. The mean age (±SD) of the 401 participants was 47.1 ± 11.7 years. Four in 10 participants had stage III (41.9%; n = 168) and over a third (34.7%; n = 140) stage IV cancers. The median interval from first consultation to diagnosis, i.e. diagnostic interval (DI) was 5.6 months (IQR: 1.5-17.0), while the median interval from histological diagnosis to start of chemotherapy, i.e. pre-treatment interval (PTI) was 1.7 months (IQR: 0.7-4.5). Majority (85%, n = 341) of participants were diagnosed at ≥3 months from first consultation with clinicians. Participants with tertiary education and those who lived within 100-199 km from the UCI were about four times and twice more likely to be diagnosed early (DI <3 months from first consultation) ([aPR = 3.88; 95% CI: 1.15-13.0] and [aPR = 2.19; 95% CI: 1.06-4.55]), respectively. About half (48.3%; n = 176) of participants started chemotherapy within 1 month of cancer diagnosis. Patients who lived more than 300 km from the UCI were less likely to start chemotherapy within 1 month of histology diagnosis of cancer. [Correction added on October 17, 2023 after first online publication. The term ', i.e.' has been included in the results section in this version.] CONCLUSION: Majority of breast cancer patients are diagnosed late and in advanced stages. There is need to promote all efforts toward timely diagnosis when cancers are still in early stages by identifying factors responsible for prolonged diagnostic intervals among breast cancer patients.

Pre-treatment risk factors to predict early cisplatin-related nephrotoxicity in locally advanced head and neck cancer patients treated with chemoradiation: A single Institution experience

ObjectivesCisplatin is essential in the curative treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients. The assessment of risk factors to predict an early cisplatin-induced nephrotoxicity could help in better managing one of the most relevant cisplatin-related dose-limiting factors. Material and methodsWe retrospectively collected data of LA-HNSCC patients treated at our Institution from 2008 to 2019. Patients received cisplatin in a curative setting concurrently with radiation. Acute Kidney Injury (AKI) was assessed as a dichotomous variable (CreaIncr) based on pre-treatment values, and values recorded at days 6–20 post-first cycle of cisplatin. Univariable logistic regression models were performed to investigate associations between CreaIncr and clinical characteristics. A multivariable logistic model on a priori selected putative covariates was performed. ResultsOf the 350 LA-HNSCC treated patients, 204 were analyzed. Ninety (44 %) suffered from any grade AKI (grade I 51.1 %): out of them, 84.4 % received high-dose cisplatin (100 mg/m2 q21). On the univariable logistic regression model, male sex, age, serum uric acid, creatinine, concomitant drugs, and cisplatin schedule were significantly associated with a higher rate of AKI. At multivariable model, age (p = 0.034), baseline creatinine (p = 0.027), concomitant drugs (p = 0.043), and cisplatin schedule (one-day bolus or fractionated high-dose vs. weekly; p = 0.001) maintained their significant association. ConclusionsIdentifying pre-treatment risk factors in LA-HNSCC patients may improve decision-making in a setting where cisplatin has a curative significance. A strict monitoring of AKI could avoid cisplatin dose adjustments, interruptions, and treatment delays, thus limiting a negative impact on outcomes.

Functional Outcomes and Toxicities Associated with SBRT to Bone Metastases Involving the Joint Space

Metastatic spread to bone is a common occurrence in advanced malignancies. Stereotactic Body Radiation Therapy (SBRT) is increasingly used for management of bone metastases in both the palliative and oligometastatic settings, especially for radioresistant histologies. Historically, therapeutic radiation to joints has been avoided whenever possible to minimize toxicities such as joint fibrosis and stiffness. Very little data exists to guide the treatment of bone metastases involving or adjacent to the joint space using SBRT. The purpose of this study is to report functional outcomes and toxicities associated with SBRT to metastatic bone lesions involving the joint space. Patients with solid tumor bone metastases involving the joints of long bones who were treated with SBRT (≥500 cGy/fraction; BED10 ≥37.5) who had ≥30 days follow up were identified from our institutional electronic health record using an IRB approved protocol. Pre-treatment and post-treatment pain assessments and toxicities were collected and scored retrospectively. Toxicities were categorized as acute (≤30 days post treatment) or late (>30 days post-treatment). Weidentified 40 evaluable patients with 54 lesions treated with SBRT. Lesions treated included those involving the hip (29/54, 54%), shoulder (11/54, 20%), elbow (8/54, 14%), and knee (6/54, 11%). The most common patient histology treated was renal cell carcinoma (13/40, 33%), followed by prostate adenocarcinoma (7/40, 18%), non-small cell lung cancer (4/40, 10%), and breast cancer (4/40, 10%). The remainder (12/40) had other histologies. Median follow up time was 7.7 months (range = 1.3-55.0). Median prescribed dose was 650 cGy/fraction (range = 500-1300 cGy) and most lesions received 4000 cGy in 5 fractions (18/54, 33%). At >30 days, of the 42 sites where pain was reported pre-treatment, 30/42 (71%) had complete or partial pain relief, while 10/42 (24%) experienced no pain relief during available follow up. Patients reported worsening pain after SBRT in 2/54 (3.7%) of treated lesions. Seven of 54 (14.0%) treated lesions led to complaints of joint stiffness requiring physical therapy. A minority of patients developed insufficiency fractures or treatment failures after SBRT requiring surgery (4/54, 7.4%). Three of 54 patients (5.6%) developed symptomatic radiation myositis confirmed on imaging. Toour knowledge, this is the first study to report functional and toxicity outcomes of SBRT to lesions involving the joints of long bones. While SBRT appears to have acceptable toxicities at the doses reported in this analysis, further study is warranted to identify pre-treatment factors predictive of toxicity. Limitations of the study include its small sample size, retrospective nature, and single institution design. Future studies will focus on dosimetric and clinical factors associated with toxicities which may allow for more personalized treatments and assist with informed consent.

Risk factors of low-level viremia in chronic hepatitis B patients receiving Entecavir monotherapy: a retrospective cohort study.

Low-level viremia (LLV), a special case of poor response to antiviral therapy, has become a focus of liver disease research; however, most studies have focused on poor response to antiviral therapy, and little attention has been paid to LLV. Therefore, this study aimed to investigate the factors influencing LLV in patients with chronic hepatitis B (CHB) receiving entecavir (ETV) monotherapy. Clinical data of CHB patients receiving ETV treatment for at least 1year at the outpatient department of the Affiliated Hospital of Xuzhou Medical University from November 2018 to June 2020 were collected. Patients were divided into LLV (180 cases) and sustained virological response (SVR) groups (337 cases) according to the hepatitis B virus (HBV) DNA load at the end of the observation period. Demographic features and laboratory markers were also examined. Univariate and multivariate logistic regression analyses were performed to examine factors influencing LLV in patients receiving long-term ETV monotherapy. Significant differences were noted between the LLV and SVR groups in terms of age, sex, presence or absence of cirrhosis, HBeAg positivity rate, baseline HBV DNA load, and baseline HBsAg level before treatment. Multivariate logistic regression analysis showed that baseline HBeAg status, HBV DNA load, and HBsAg quantification were pretreatment risk factors for LLV in long-term ETV antiviral therapy. CHB patients with a high HBV DNA load, high HBsAg quantification, and positive HBeAg results tend to have a high risk of LLV despite long-term ETV antiviral treatment and should be dynamically monitored.

Accelerated fixation is associated with fewer pulmonary embolism in patients with isolated and unilateral femoral shaft fractures: A TQIP analysis

IntroductionThe optimal time to intramedullary internal fixation for patients with isolated and unilateral femoral shaft fractures was investigated by the American College of Surgeons-Trauma Quality Improvement Program (ACS-TQIP). Material and methodsAdult patients from the TQIP between 2017 and 2019 were eligible for inclusion. The associations between time to fixation and target outcomes (pulmonary embolism [PE], deep vein thrombosis [DVT], acute respiratory distress syndrome [ARDS], and mortality) were assessed. Maximization of the sum of sensitivity and specificity was used to determine the optimal cut point. The patients were divided into three groups according to different time to fixation intervals. A multinomial propensity scores weighting using generalized boosted models was performed for all unbiased pre-treatment factors between the groups. Multivariate logistic regression was used to clarify the outcomes predictors. ResultsThe univariate and multivariate analysis before weighting showed that only PE was significantly associated with time to fixation (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.09; p = 0.012). The optimal cut point of time to fixation was 13.88 h. The patients were divided into accelerated (≤ 13.88 h), standard (> 13.88 and ≤ 24 h), and delayed (> 24 and < 36 h) groups. After weighting for all unbiased pre-treatment factors between the groups, multivariate logistic regression showed that standard group significantly increased the risk of PE compared with accelerated group (OR, 4.436; 95% CI, 1.844-10.672; p = 0.001). ConclusionAccelerated intramedullary internal fixation within 13.88 h was associated with a significantly decreased risk of PE compared with standard fixation in patients with isolated and unilateral femoral shaft fractures without additional mortality risks.

A predictive survival model for patients with stage IV oropharyngeal squamous cell carcinoma treated with chemoradiation.

To evaluate the pre-treatment and post-treatment clinical factors associated with rate of survival at 1, 3, and 5years in stage IV oropharyngeal cancer patients treated with concurrent chemoradiation with/without neoadjuvant chemotherapy. This retrospective cohort study involved 128 Stage IV oropharyngeal cancer patients that were treated at our tertiary referral center between 2008 and 2020. The pre-treatment and post-treatment clinical parameters including nutritional status and inflammatory markers were retrospectively reviewed. The 5-year overall survival rate for all patients was 36.72%. The disease-specific survival (DSS) at 1-year and 3-year were 80% and 63%, whereas the disease-free survival (DFS) at 1-year and 3-year were 49% and 40%, respectively. In multivariate analyses, pretreatment hemoglobin (Hb) < 12g/dL (hazard ratio [HR] 2.551, 95% confidence interval [CI] 1.366-4.762, p = 0.003), pretreatment systemic immune inflammation (SII) ≥ 1751 (HR 2.173, 95% CI 1.015-4.652, p = 0.046), and posttreatment systemic inflammation response index (SIRI) ≥ 261 (HR 2.074, 95% CI 1.045-4.115, p = 0.037) were independent indicators for worsened DSS. Pretreatment Hb < 12g/dl (HR 1.692, 95% CI 1.019-2.809, p = 0.032), pretreatment SII ≥ 1751 (HR 1.968, 95% CI 1.061-3.650, p = 0.032), and posttreatment SII ≥ 1690 (HR 1.922, 95% CI 1.105-3.345, p = 0.021) were independent indicators for worsened DFS. A nomogram was developed using pretreatment Hb, pretreatment SII, and posttreatment SIRI to forecast DSS. The pretreatment Hb, pretreatment SII, posttreatment SII, and posttreatment SIRI are associated with survival in patients with stage IV oropharyngeal cancers. The developed nomogram aids in survival prediction and treatment adjustment.

Predictors of treatment efficacy with nucleos(t)ide analogues for chronic hepatitis B

Chronic hepatitis B virus (HBV) infection remains a global public health problem. Patients with chronic HBV infection are at increased risk of progression to cirrhosis and development of hepatocellular carcinoma (HCC). The primary goal of therapy is to improve quality of life and survival by preventing disease progression to cirrhosis, HCC, and death. Induction of long-term suppression of HBV replication represents the most important goal of current treatment strategies, and clearance of hepatitis B surface antigen (HBsAg) is its optimal endpoint. Long-term administration of potent nucleos(t)ides analogues (NA) with a high barrier to resistance (entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide) is the therapy of choice. However, factors associated with response to NA-based antiviral therapy (ART) are not clear and have not been included in treatment recommendations. The purpose of this review is to summarize the results of studies evaluating the influence of factors on the effectiveness of NA-based ART. The study examined the significance of baseline pre-treatment factors (demographic, histological, virological, biochemical) as well as dynamic changes in viral load and HBsAg levels during ART in predicting treatment efficacy.

Partial ulnar ostectomy, stereotactic body radiation therapy, and palliative radiation therapy as local limb sparing treatment modalities for ulnar tumors in dogs.

Information on dogs that undergo limb preserving local treatment for ulnar tumors is currently limited. To describe the clinical characteristics and outcomes in dogs that underwent partial ulnectomy or radiation therapy (RT) for ulnar bone tumors, and to evaluate potential risk factors for outcomes as well as pre-treatment factors for association with treatment modality selected. Forty client-owned dogs that underwent partial ulnectomy or RT for an ulnar tumor from July 2006 to July 2021. The medical records database from a single institution were retrospectively reviewed, and data were recorded and analyzed. Radiation therapy was performed in 24 dogs, with 12 stereotactic body RT (SBRT) and 12 palliative RT (PRT) plans, and partial ulnectomy was performed in 16 dogs. Biomechanical complications occurred in 6/12 (50%) dogs that underwent SBRT, 6/12 (50%) dogs that underwent PRT, and 3/16 (18.8%) dogs that underwent ulnectomy. The majority of dogs had a good functional outcome following partial ulnectomy, and no dogs required surgical stabilization of the carpus even with lateral styloid process excision. Pathologic fracture occurred in 4/12 (33.3%) dogs following SBRT and 5/12 (41.7%) dogs following PRT. Local progression or recurrence was documented in 5/12 (41.7%) dogs that underwent SBRT, 2/12 (16.7%) dogs that underwent PRT, and 2/16 (12.5%) dogs that underwent ulnectomy. The overall median survival time was 198 days, and factors that were significantly associated with improved survival time included adjuvant chemotherapy administration and partial ulnectomy as local treatment method for dogs that received chemotherapy. Both RT and ulnectomy were effective and well tolerated local treatment modalities for dogs with ulnar tumors.

Post-treatment neutrophil to lymphocyte ratio as a prognostic tool in patients treated with tocilizumab for severe COVID-19 pneumonia - a single center experience.

Tocilizumab is used in patients with severe COVID-19 pneumonia and high concentration of IL-6. We studied potential prognostic role of neutrophil and lymphocyte count regarding tocilizumab treatment. We enrolled 31 patients with severe COVID-19 pneumonia and higher serum IL-6 concentration. The samples were taken on the day of tocilizumab administration and five days later. We used ROC analysis to investigate the association between the analysed parameters and 30-day mortality in order to determine the best pre-treatment and post-treatment prognostic factor. Kaplan-Meier curves and log-rank test were used to present and to analyse the difference in survival. Patients had a median age of 63 (55-67) years and were treated with a median tocilizumab dose of 800 mg. During the 30-day follow-up period, 17 patients died (30-day mortality 54%). Among pre-treatment variables, neutrophil count had the best prognostic accuracy (AUC 0.81, 95%CI: 0.65-0.96, P = 0.004), while neutrophil to lymphocyte ratio (NLR) had the highest accuracy among post-treatment variables in predicting 30-day mortality (AUC 0.94, 95%CI: 0.86-1.00, P < 0.001). Among post-treatment parameters, neutrophil count and NLR were equally good prognostic factors. Post-treatment NLR cut-off of 9.8 had the sensitivity of 81% and specificity of 93%. Patients with NLR ≥ 9.8 had the median survival of 7.0 (3-10) days vs. median survival not reached in patients with NLR < 9.8 (P < 0.001). Pre-treatment and post-treatment neutrophil count with post-treatment NLR may represent prognostic tools for patients with higher IL-6 concentration in severe COVID-19 pneumonia treated with tocilizumab.

Real-world treatment outcomes of patients with penile cancer in the Kyushu-Okinawa area of Japan in the pre-guideline era.

To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter≥30mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status≥1, cT≥3, cN≥2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN≥2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P=0.0002), Eastern Cooperative Oncology Group performance status≥1 (4.42; 1.79-10.9; P=0.0012) and cT≥3 (3.34; 1.11-10.1; P=0.0319) were identified as independent prognostic factors. The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN≥2, Eastern Cooperative Oncology Group performance status≥1 and cT≥3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.

FRI-440 - Histological inflammation in severe alcohol-related hepatitis is the main pre-treatment factor associated to glucocorticoid response

FRI-440 - Histological inflammation in severe alcohol-related hepatitis is the main pre-treatment factor associated to glucocorticoid response

A Photodynamic Therapy Index for Central Serous Chorioretinopathy to Predict Visual Prognosis Using Pretreatment Factors

This study aimed to establish a treatment index based on functional outcomes of photodynamic therapy (PDT) for central serous chorioretinopathy (CSC). A retrospective clinical case-control study. This was a single-institute study. Eighty eyes with CSC, who are treated by PDT and whose subretinal fluid resolves within six months, were divided into two groups: those with poor visual outcome (PVO) (best-corrected visual acuity [BCVA] ≤0.5 six months post-PDT), and the remaining eyes (better visual outcome [BVO]). The areas under the curve (AUC) and cutoff values from receiver operating characteristic curves were examined. This was used to predict the groups using pretreatment BCVA and the thickness of each retinochoroidal layer. Twenty-one eyes were in the PVO group and 59 eyes in the BVO group. The AUCs were 0.959 for BCVA, 0.959 for the thickness from the internal limiting membrane to the external limiting membrane (IET), 0.820 for the thickness from the external limiting membrane to the photoreceptor outer segment layer, 0.715 for the subfoveal retinal thickness, and 0.515 for the subfoveal choroidal thickness. The BCVA and IET cut-off values were 0.267 logMAR and 71.5 μm, respectively. Using the combination of the cutoff values of BCVA and IET, the highest values for the sensitivity, specificity, positive predictive value, and negative predictive value were 95.2%, 94.9%, 85.0%, and 98.0%, respectively. The combination of pre-PDT BCVA and IET in CSC can accurately predict the post-treatment visual prognosis. These values could be used as a treatment index of PDT for CSC.

Pretreatment and Posttreatment Factors Associated with Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

Hydrocephalus is a common complication after aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to evaluate novel preoperative and postoperative risk factors for shunt-dependent hydrocephalus (SDHC) after aSAH via a systematic review and meta-analysis. A systematic search was conducted using PubMed and Embase databases for studies pertaining to aSAH and SDHC. Articles were assessed by meta-analysis if the number of risk factors for SDHC was reported by >4 studies and could be extracted separately for patients who did or did not develop SDHC. Thirty-seven studies were included, comprising 12,667 patients with aSAH (SDHC 2214 vs. non-SDHC 10,453). In a primary analysis of 15 novel potential risk factors, 8 were identified to be significantly associated with increased prevalence of SDHC after aSAH, including high World Federation of Neurological Surgeons grades (odds ratio [OR], 2.43), hypertension (OR, 1.33), anterior cerebral artery (OR, 1.36), middle cerebral artery (OR, 0.65), and vertebrobasilar artery (2.21) involvement, decompressive craniectomy (OR, 3.27), delayed cerebral ischemia (OR, 1.65), and intracerebral hematoma (OR, 3.91). Several new factors associated with increased odds of developing SDHC after aSAH were found to be significant. By providing evidence-based risk factors for shunt dependency, we describe an identifiable list of preoperative and postoperative prognosticators that may influence how surgeons recognize, treat, and manage patients with aSAH at high risk for developing SDHC.

MP43-03 CLOMIPHENE CITRATE IN IDIOPATHIC NON-OBSTRUCTIVE AZOOSPERMIA

You have accessJournal of UrologyCME1 Apr 2023MP43-03 CLOMIPHENE CITRATE IN IDIOPATHIC NON-OBSTRUCTIVE AZOOSPERMIA Mohamed S. Kattan, Bader Akroof, Katherine Lajkosz, Ethan Grober, Keith Jarvi, and Kirk Lo Mohamed S. KattanMohamed S. Kattan More articles by this author , Bader AkroofBader Akroof More articles by this author , Katherine LajkoszKatherine Lajkosz More articles by this author , Ethan GroberEthan Grober More articles by this author , Keith JarviKeith Jarvi More articles by this author , and Kirk LoKirk Lo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003289.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Clomiphene citrate (CC) is a selective estrogen receptor modulator (SERM). Empirical off-label use of CC in men with infertility has existed for almost 50 years, yet there is not enough evidence to support its use in non-obstructive azoospermia (NOA) patients. This study aims to evaluate the efficacy of CC in sperm production in NOA, and determine the predictors for success. METHODS: A prospective study was conducted on patients who presented with idiopathic NOA from 2015-2022. Patients were evaluated with history, physical examination, karyotyping, scrotal ultrasound, semen and hormonal assessment pre and at least 3 months post treatment. Patients were treated with CC. Patients with abnormal karyotype, positive Y micro-deletion or history of testosterone use were excluded. Patients with cryptospermia were included but analyzed separately. Differences in pre-treatment characteristics by response status were evaluated using Mann-Whitney U tests. ROC analysis was conducted to select the optimal cut-offs for predicting response. 60 patients met the inclusion criteria; 48 azoospermic patients (group A), 12 cryptospmic patients (group B). Response is defined as presence of any sperm in the ejaculate for (group A) and as sperm concentration ≥10000 sperm/ml for (group B). RESULTS: 8/48 (16.6%) in group A had sperm in the ejaculate with CC (concentration mean 0.51×106/mL: sd 0.77×106 /mL: range 0.02–2.14). 8/12 (66.6%) in group B had ≥10000 sperm/mL (mean 1.4×106 /mL: sd 1.83×106/mL: range 0.1-5.90). Of the 8 responders in group A: 3 responded within 3 months, 3 responded at 3-6 months 2 responded at 6-9 months. Median time to response was 3.6 months (IQR: 2.8-6.0, range: 0.7-6.8 months). Among all pre-treatment factors analyzed, only testosterone level trended towards statistical significance (p-value: 0.08). The optimal cut-off levels are shown in Table1. CONCLUSIONS: Approximately 1 in 6 patients with idiopathic NOA treated with CC showed sperm in the ejaculate. Those patients could potentially avoid surgical sperm extraction for in vitro fertilization (IVF). Pre-treatment hormonal levels seem to be the best indicator for response with the optimal levels shown in this study. The duration of response may vary where some patients require more than 3-6 months of treatment. Future studies should focus on the success of IVF results in men with NOA on CC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e602 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed S. Kattan More articles by this author Bader Akroof More articles by this author Katherine Lajkosz More articles by this author Ethan Grober More articles by this author Keith Jarvi More articles by this author Kirk Lo More articles by this author Expand All Advertisement PDF downloadLoading ...