Treatment Outcomes In Patients Research Articles

Yap methylation-induced FGL1 expression suppresses anti-tumor immunity and promotes tumor progression in KRAS-driven lung adenocarcinoma.

Despite significant strides in lung cancer immunotherapy, the response rates for Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven lung adenocarcinoma (LUAD) patients remain limited. Fibrinogen-like protein 1 (FGL1) is a newly identified immune checkpoint target, and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients. This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS-mutated cancer. The expression levels of FGL1 and SET1 histone methyltransferase (SET1A) in lung cancer were assessed using public databases and clinical samples. Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models. The effects of FGL1 and Yes-associated protein (Yap) on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry. Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A-directed transcriptional program. Upregulation of FGL1 expression in KRAS-mutated cancer was inversely correlated with the infiltration of CD8+ T cells. Mechanistically, KRAS activated extracellular signal-regulated kinase 1/2 (ERK1/2), which subsequently phosphorylated SET1A and increased its stability and nuclear localization. SET1A-mediated methylation of Yap led to Yap sequestration in the nucleus, thereby promoting Yap-induced transcription of FGL1 and immune evasion in KRAS-driven LUAD. Notably, dual blockade of programmed cell death-1 (PD-1) and FGL1 further increased the therapeutic efficacy of anti-PD-1 immunotherapy in LUAD patients. FGL1 could be used as a diagnostic biomarker of KRAS-mutated lung cancer, and targeting the Yap-FGL1 axis could increase the efficacy of anti-PD-1 immunotherapy.

Evaluating ECM stiffness and liver cancer radiation response via shear-wave elasticity in 3D culture models

BackgroundThe stiffness of the tumor microenvironment (TME) directly influences cellular behaviors. Radiotherapy (RT) is a common treatment for solid tumors, but the TME can impact its efficacy. In the case of liver cancer, clinical observations have shown that tumors within a cirrhotic, stiffer background respond less to RT, suggesting that the extracellular matrix (ECM) stiffness plays a critical role in the development of radioresistance.MethodsThis study explored the effects of ECM stiffness and the inhibition of lysyl oxidase (LOX) isoenzymes on the radiation response of liver cancer in a millimeter-sized three-dimensional (3D) culture. We constructed a cube-shaped ECM-based millimeter-sized hydrogel containing Huh7 human liver cancer cells. By modulating the collagen concentration, we produced two groups of samples with different ECM stiffnesses to mimic the clinical scenarios of normal and cirrhotic livers. We used a single-transducer system for shear-wave-based elasticity measurement, to derive Young’s modulus of the 3D cell culture to investigate how the ECM stiffness affects radiosensitivity. This is the first demonstration of a workflow for assessing radiation-induced response in a millimeter-sized 3D culture.ResultsIncreased ECM stiffness was associated with a decreased radiation response. Moreover, sonoporation-assisted LOX inhibition with BAPN (β-aminopropionitrile monofumarate) significantly decreased the initial ECM stiffness and increased RT-induced cell death. Inhibition of LOX was particularly effective in reducing ECM stiffness in stiffer matrices. Combining LOX inhibition with RT markedly increased radiation-induced DNA damage in cirrhotic liver cancer cells, enhancing their response to radiation. Furthermore, LOX inhibition can be combined with sonoporation to overcome stiffness-related radioresistance, potentially leading to better treatment outcomes for patients with liver cancer.ConclusionsThe findings underscore the significant influence of ECM stiffness on liver cancer’s response to radiation. Sonoporation-aided LOX inhibition emerges as a promising strategy to mitigate stiffness-related resistance, offering potential improvements in liver cancer treatment outcomes.

Treatment of Symptomatic Carotid Webs

The present study aims to describe the clinical characteristics and treatment outcomes of patients with symptomatic carotid web treated at a single institution in South America. Retrospective study of a single-center experience of patients with carotid webs surgically treated from September 2019 to September 2023. 10 patients had carotid webs, six (60%) were females. Median age was 54.5 years (range: 35-77 years). All patients were symptomatic. Diagnosis was made in 90% (n=9) of the patients with either computed tomography angiography or magnetic resonance alone. One (10%) patient underwent angiography for definite diagnosis. The median interval from the first neurological event to intervention was 90 months (range: 3 days- 108 months). Four (40%) patients underwent surgical treatment within one month from symptom onset and carotid web diagnosis, with a median of 3.5 days (range: 3-9 days). Six (60%) patients underwent delayed surgical treatment since the cause of the neurological event was uncertain, with a median of 54 months (range: 6 - 108 months). These six patients had recurrent neurological events. Three (30%) patients underwent carotid endarterectomies with polyurethane patch and three (30%) by eversion technique. Three (30%) patients underwent segmental resection and reanastomosis of the internal carotid artery. One underwent internal carotid artery plasty with saphenous vein. At a median follow-up of 30 months (range: 6-46 months), one patient persists with mild aphasia, another patient has severe aphasia and right hemiparesis, both as sequalae of their initial strokes, and another patient has suffered 3 non-ischemic episodes of brief transient right hemiparesis attributed to epileptic seizures. The other seven patients remain without new neurological events. Neurological events of carotid distribution deserve accurate imaging work up, keeping in mind the diagnosis of carotid web. Surgical treatment for carotid web seems effective for preventing recurrences; nevertheless, further studies are warranted to define the best management for these patients.

Survival of Children with Acute Lymphoblastic Leukemia with Risk Group-Based Protocol Changes: A Single Center Experience with 460 Patients over a 20-Year Period.

Recent treatments for pediatric acute lymphoblastic leukemia (ALL) are founded on risk stratification. We examined the survival rates and prognostic factors of patients over a 20-year period at a single institution. This study analyzed patients diagnosed with ALL and treated at the Pediatric Department of Samsung Medical Center (SMC). Patients were categorized into standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. The SMC protocol for the HR group underwent two changes during the study period: A modified Children's Cancer Group (CCG)-1882 protocol was used from 2000 to 2005, the Korean multicenter HR ALL-0601 protocol from 2006 to 2014, and the Korean multicenter HR ALL-1501 protocol from 2015 to 2019. Of the 460 patients, complete remission was achieved in 436 patients (94.8%). The 10-year overall survival rate (OS) was 83.8±1.9% for all patients. OS according to the SMC risk group was as follows: 95.9±1.4% in the SR group, 83.8±3.6% in the HR group, and 66.2±6.9% in the VHR group. The 5-year OS within the HR group varied according to the treatment protocol: 73.9±7.5%, in the modified CCG-1882 protocol, 83.0±3.9%, in the 0601 protocol, and 96.2±2.6%, in the 1501 protocol. For those aged 15 years and older, the OS was only 56.5±13.1%. Relapse occurred in 71 patients (15.4%), and the OS after relapse was 37.7±6.0%. The treatment outcomes of patients with ALL improved markedly. However, there is a need to further characterize adolescents and young adult patients, as well as those who have experienced relapses.

The prognostic impact of the pan-immune-inflammation value (PIV) on the efficacy of treatment and clinical outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC)

Aims: This study aimed to assess the prognostic and predictive implications of pre-treatment pan-immune-inflammation value (PIV) on treatment efficacy and clinical outcomes in patients with extensive-stage small-cell lung cancer (ES-SCLC), comparing it with established indices such as the systemic immune-inflammation index (SII) and neutrophil to lymphocyte ratio (NLR). Methods: A retrospective cohort study included 70 patients diagnosed with ES-SCLC treated with standard chemotherapy with or without immune checkpoint inhibitors. PIV was calculated as PIV=(neutrophils×platelets×monocytes)÷lymphocytes. Patients were categorized into low PIV (

Assessment of Zygomaticomaxillary Suture Maturation in Patients With Unilateral Cleft Lip and Palate: Implications for Orthodontic Treatment Planning.

Introduction The zygomaticomaxillary suture (ZMS) is vital for craniofacial development and orthodontic treatment planning. Located at the junction of the zygomatic and maxillary bones, the ZMS undergoes significant changes during growth, affecting midfacial morphology and stability. Understanding ZMS maturation is essential for optimizing orthodontic interventions, especially in patients with cleft lip and palate (CLP), who often exhibit altered craniofacial growth patterns due to congenital deformities and surgical interventions. Methodology A retrospective analysis was conducted with 50 participants, including 25 patients with unilateral CLP and 25 age-matched controls. Clinical and radiographic data, including lateral cephalometric radiographs and cone-beam computed tomography (CBCT) scans, were collected to assess ZMS maturation stages. The stages, ranging from immature (stage 0) to fully mature (stage 4), were evaluated using established radiographic criteria. Statistical analyses, including Chi-square tests and logistic regression, were performed to compare the distribution of maturation stages between groups. Results Significant differences were observed in ZMS maturation stages between the cleft side, non-cleft side, and control group. The cleft side exhibited a higher prevalence of immature (stage 0) and early maturation (stage 1) stages compared to the control group, with mean values of 4 ± 1.2 and 5 ± 1.3, respectively. The control group showed a higher prevalence of fully mature (stage 4) sutures, with a mean value of 8 ± 1.4. The p-values for stages 0, 1, and 4 were 0.045, 0.034, and 0.039, respectively, indicating statistical significance. The findings highlight distinct maturation patterns in CLP patients, with delayed ZMS maturation on the cleft side. This suggests the need for tailored orthodontic interventions to accommodate prolonged growth phases in CLP patients. The study underscores the importance of detailed ZMS assessments for personalized treatment planning. Future research should focus on longitudinal studies to further understand CLP's impact on craniofacial development. Conclusion Assessing ZMS maturation provides critical insights for optimizing orthodontic and surgical treatment outcomes in CLP patients. By identifying specific developmental delays and tailoring interventions accordingly, clinicians can improve the effectiveness and stability of treatments. This study contributes to the growing body of evidence supporting individualized treatment plans based on precise developmental assessments.

The impact of digital inequities on salivary gland cancer disparities in the United States.

Technology and internet access have become increasingly integrated into healthcare as the primary platform for health-related information and provider-patient communication. Disparities in access to digital resources exist in the United States and have been shown to impact health outcomes in various head and neck malignancies. Our objective is to evaluate the associations of digital inequity on health outcomes in patients with salivary gland cancer (SGC). The Digital Inequity Index (DII) was developed using 17 census-tract level variables obtained from the American Community Survey and Federal Communications Commission. Variables were categorized as digital infrastructure or sociodemographic (e.g., non-digital) and scored based on relative rankings across all US counties. Scores were assigned to patients from the Surveillance-Epidemiology-End Results (SEER) database diagnosed with SGC between 2013 and 2017 based on county-of-residence. Regressions were performed between DII score and outcomes of surveillance time, survival time, tumor stage at time of diagnosis, and treatment modality. Among 9306 SGC-patients, increased digital inequity was associated with advanced-staging at presentation (OR: 1.04, 95% CI: 1.01-1.07, p = 0.033), increased odds of chemotherapy receipt (OR: 1.05, CI: 1.01-1.10, p = 0.010), and decreased odds of surgical intervention (OR: 0.94, 95% CI: 0.91-0.98, p = 0.003) after accounting for traditional sociodemographic factors. Increased digital inequity was also associated with decreased surveillance time and survival periods. Digital inequity significantly and independently associates with negative health and treatment outcomes in SGC patients, highlighting the importance of directed efforts to address these seldom-investigated drivers of health disparities.

Recent developments in the field of radiotherapy for the management of lung cancer.

Lung cancer has a poor prognosis, and further improvements in outcomes are needed. Radiotherapy plays an important role in the treatment of unresectable lung cancer, and there have been recent developments in the field of radiotherapy for the management of lung cancer. However, to date, there have been few reviews on the improvement in treatment outcomes associated with high precision radiotherapy for lung cancer. Thus, this review aimed to summarize the recent developments in radiotherapy techniques and indicate the future directions in the use of radiotherapy for lung cancer. Stereotactic body radiotherapy (SBRT) for unresectable stage I lung cancer has been reported to improve local control rates without severe adverse events, such as radiation pneumonitis. For locally advanced lung cancer, a combination of chemoradiotherapy and adjuvant immune checkpoint inhibitors dramatically improves treatment outcomes, and intensity-modulated radiotherapy (IMRT) enables safer radiation therapy with less frequent pneumonitis. Particle beam therapy, such as carbon-ion radiotherapy and proton beam therapy, has been administered as advanced medical care for patients with lung cancer. Since 2024, it has been covered under insurance for early stage lung cancer with tumors ≤ 5cm in size in Japan. In addition to chemotherapy, local ablative radiotherapy improves treatment outcomes in patients with oligometastatic stage IV lung cancer. A particular problem with radiotherapy for lung cancer is that the target location changes with respiratory motion, and various physical methods have been used to control respiratory motion. Recently, coronavirus disease has had a major impact on lung cancer treatment, and cancer treatment during situations, such as the coronavirus pandemic, must be performed carefully. To improve treatment outcomes for lung cancer, it is necessary to fully utilize evolving radiotherapy modalities, and the role of radiotherapy in lung cancer treatment is expected to increase.

Diagnosis, Treatment Patterns, and Outcomes in Real-World Patients with RET Fusion-Positive Non-small Cell Lung Cancer in China.

Epidemiological studies on non-small cell lung cancer (NSCLC) have noted RET fusions as an oncogenic driver. However, real-world data on RET biomarker testing and treatment patterns in China remain limited. This study aimed to examine demographics, clinical and molecular features, and RET testing and treatment patterns and outcomes in patients with RET fusion-positive NSCLC. Utilizing real-world data from the Chinese Multi-center Lung Cancer Precision Medicine Registry, this retrospective cohort study focused on Chinese patients diagnosed with RET fusion-positive NSCLC between January 1, 2016, and November 30, 2021. The cohort was divided into early-stage and advanced-stage subgroups. Demographics, clinical and molecular profiles, treatment received, and outcomes including real-world event free survival (rwEFS), real-world progression free survival (rwPFS), and overall survival (OS) were assessed. The study included 121 patients with RET fusion-positive NSCLC, comprising 80 early-stage and 58 advanced-stage patients. High biomarker testing rates were observed at diagnosis (75% for early-stage, 78% for advanced-stage). RET testing was often conducted via tissue samples (95.9%) and next-generation sequencing (89.3%). KIF5B (57.0%) and CCDC6 (20.7%) were the most common gene fusion partners. The most frequent oncogenic mutations were TP53 (15.7%) and EGFR (6.6%). Platinum-based chemotherapy was the most common first-line treatment among advanced-stage patients. Median rwPFS was 9.22months for advanced-stage patients on first-line chemotherapy, and median OS was 30.7months for all advanced-stage patients. The 2-year rwEFS rate for early-stage patients was 86.0%, with a median OS of 91.9months. The study observed high biomarker testing rates at initial diagnosis for early- and advanced-stage RET fusion-positive NSCLC patients in China. The heterogeneous treatment pattern of advanced patients suggests the need for more precise, evidence-based treatment to guide clinical decisions. Given the existing therapeutic regimens fall short of adequately addressing treatment needs, targeted therapies are essential to improve outcomes.

Tolerability and Outcomes for Treatment of Older Myxoid Liposarcoma Population.

Myxoid liposarcoma predominantly affects young and middle-aged individuals, and little is known regarding treatment tolerability and outcomes in older patients. This study aims to better understand this older patient population. This single institution retrospective study included patients aged 70 years and older with localized (non-metastatic) myxoid liposarcoma. Sixteen patients were included. The median age was 75 years, and 9 (56%) were female. Fourteen (88%) were extremity tumors and two (12%) were trunk. The median tumor size was 10.4 cm (range, 3.6 to 28 cm). Five (31%) tumors had a round cell component. All patients had surgery. Fourteen (88%) had perioperative radiation, and three (19%) had perioperative chemotherapy. One patient had postoperative infection, and one patient had neutropenic fever from preoperative chemotherapy. The median follow up from surgery was 6.3 years. Eight (50%) patients died from MLPS. The median relapse-free survival and overall survival were 34 months and 75 months, respectively. Most older patients with localized MLPS received perioperative radiation therapy with surgery, and few serious toxicities were reported. Even with treatment, half of the patients relapsed.

Abstract PR011: Investigating the interplay among allostatic load, social determinants of health, and treatment outcomes in chronic myeloid leukemia patients

Abstract Introduction. The advent of tyrosine kinase inhibitors (TKIs) has transformed chronic myeloid leukemia (CML) into a chronic condition, allowing many patients (pts) to achieve survival rates comparable to the general population. Yet, most pts patients require lifelong therapy, regular follow-up, and management of TKI side effects, posing challenges within the healthcare system alongside structural and financial barriers. We have previously found that CML pts with an allostatic load (AL) burden indicating cumulative stress, experience worse treatment outcomes. In light of this, we investigated whether AL is a biological indicator of social determinants of health (SDH) and its correlation with CML treatment outcomes. Methods. We conducted a single-institution retrospective study, enrolling CML pts and assessing 23 biomarkers across four domains (cardiovascular, metabolic, immunologic, and neuroendocrine) required to calculate the AL score at the time of the first visit. Pts were sorted into low and high AL groups using the cohort's median score of 5 as the threshold. SDH was evaluated at both individual and population levels by integrating data from medical records with the SDH database from the Agency for Healthcare Research and Quality. Statistical analyses, including chi-square and Fisher’s exact tests, were conducted with significance set at p<0.05. Results. Between 2003 and 2023, data from 108 CML pts undergoing first-line treatment were retrieved. Pts with high AL were more likely to be older (mean age 53.8 vs. 47.2 years, p=0.03), and a greater proportion were identified as Black compared to those in the low AL cohort (25.5% vs. 12.3%, p=0.01). We identified an association between high AL and overall mortality (13.7% vs. 1.8%, p=0.02), with effects trending towards a higher risk of CML-specific death (6.4% vs. 0, p=0.05). Higher AL was correlated with adverse SDH, such as reliance on public health insurance (32% vs. 52.2%, p=0.04), living alone (67.7% vs. 86.8%, p=0.05), and lack of regular exercise (38.9% vs. 7.4%, p=0.01). Geographic inequality was identified, as patients with high AL were more likely to reside in Georgia (GA) compared to South Carolina and other states (66.7% vs. 27.5% vs. 5.9%, p=0.01). Indeed, pts in GA who traveled shorter distances to the treatment facility and resided in areas with higher particulate matter levels, as an indicator of air pollution, were less likely to achieve major molecular response (p=0.011 and p=0.008, respectively). SDH such as regular exercise, home environment, and health insurance were associated with overall and CML-specific survival. However, birth country, language, household income, and education, were not associated with either AL or treatment outcomes. Conclusion. Adverse SDH significantly amplifies the burden of AL, serving as a comprehensive indicator of chronic stress, health behaviors, and environmental conditions. Our findings highlight the intricate interplay between social, economic, and environmental factors in shaping treatment outcomes among CML patients. Citation Format: Marisol Miranda-Galvis, Muhannad Sharara, Kellen C. Tjioe, McKenzie Maloney Maloney, Vamsi Kota, Anand Jillella, Locke Bryan, Amany R. Keruakous, Jorge E. Cortes. Investigating the interplay among allostatic load, social determinants of health, and treatment outcomes in chronic myeloid leukemia patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr PR011.

Abstract C079: Investigating the interplay among allostatic load, social determinants of health, and treatment outcomes in chronic myeloid leukemia patients

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR011) of the Conference Program/Proceedings. Citation Format: Marisol Miranda-Galvis, Muhannad Sharara, Kellen C. Tjioe, McKenzie Maloney Maloney, Vamsi Kota, Anand Jillella, Locke Bryan, Amany R. Keruakous, Jorge E. Cortes. Investigating the interplay among allostatic load, social determinants of health, and treatment outcomes in chronic myeloid leukemia patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C079.

Real-World Treatment Patterns, Sequencing, and Outcomes in Patients with Locally Advanced or Metastatic Urothelial Carcinoma Receiving Avelumab First-Line Maintenance in the United States.

For patients with locally advanced/metastatic urothelial carcinoma (la/mUC), first-line (1L) treatment with platinum-based chemotherapy (PBC) followed by avelumab 1L maintenance (1LM) is a recommended therapy per treatment guidelines in patients without disease progression. However, contemporary real-world (rw) data among patients receiving this treatment are necessary to understand clinical outcomes and optimal treatment sequencing. This retrospective cohort study analyzed rw treatment patterns and clinical outcomes, including overall survival (rwOS) and progression-free survival (rwPFS), in patients with la/mUC receiving avelumab 1LM. From the Flatiron Health database, 214 patients who received avelumab 1LM following 1L PBC were included. From the start of avelumab 1LM, median rwOS was 23.8 months (95% CI: 18.2-not estimable [NE]) and median rwPFS was 5.1 months (95% CI: 4.1-7.0). A total of 96 patients received second-line (2L) therapy, with 53 receiving enfortumab vedotin (EV). From the start of 2L EV, median rwOS was 11.2 months (95% CI: 6.8-NE) and median rwPFS was 4.9 months (95% CI: 3.9-8.8). Treatment patterns and clinical outcomes in this study align with guidelines and outcomes observed in the JAVELIN Bladder 100 and EV-301 clinical trials and other rw studies, supporting the use of 1L PBC followed by avelumab 1LM and 2L EV for eligible patients.

OxcarNet: sinc convolutional network with temporal and channel attention for prediction of oxcarbazepine monotherapy responses in patients with newly diagnosed epilepsy

Objective.Monotherapy with antiepileptic drugs (AEDs) is the preferred strategy for the initial treatment of epilepsy. However, an inadequate response to the initially prescribed AED is a significant indicator of a poor long-term prognosis, emphasizing the importance of precise prediction of treatment outcomes with the initial AED regimen in patients with epilepsy.Approach. We introduce OxcarNet, an end-to-end neural network framework developed to predict treatment outcomes in patients undergoing oxcarbazepine monotherapy. The proposed predictive model adopts a Sinc Module in its initial layers for adaptive identification of discriminative frequency bands. The derived feature maps are then processed through a Spatial Module, which characterizes the scalp distribution patterns of the electroencephalography (EEG) signals. Subsequently, these features are fed into an attention-enhanced Temporal Module to capture temporal dynamics and discrepancies. A channel module with an attention mechanism is employed to reveal inter-channel dependencies within the output of the Temporal Module, ultimately achieving response prediction. OxcarNet was rigorously evaluated using a proprietary dataset of retrospectively collected EEG data from newly diagnosed epilepsy patients at Nanjing Drum Tower Hospital. This dataset included patients who underwent long-term EEG monitoring in a clinical inpatient setting.Main results.OxcarNet demonstrated exceptional accuracy in predicting treatment outcomes for patients undergoing Oxcarbazepine monotherapy. In the ten-fold cross-validation, the model achieved an accuracy of 97.27%, and in the validation involving unseen patient data, it maintained an accuracy of 89.17%, outperforming six conventional machine learning methods and three generic neural decoding networks. These findings underscore the model's effectiveness in accurately predicting the treatment responses in patients with newly diagnosed epilepsy. The analysis of features extracted by the Sinc filters revealed a predominant concentration of predictive frequencies in the high-frequency range of the gamma band.Significance. The findings of our study offer substantial support and new insights into tailoring early AED selection, enhancing the prediction accuracy for the responses of AEDs.

Newly diagnosed multiple myeloma with bleeding and coagulation abnormalities caused by a thrombin-inhibiting substance.

Approximately 7% of patients with newly diagnosed multiple myeloma (MM) experience bleeding complications with varying causes, but few reports have described these complications. Here we report the case of a patient with newly diagnosed MM who presented with a bleeding tendency and various coagulation abnormalities. Chromogenic assays, thrombin time, and reptilase time revealed the presence of a thrombin-inhibiting substance that inhibited release of fibrinopeptide A from fibrinogen. The coagulation abnormalities improved after treatment with daratumumab, lenalidomide, and dexamethasone. As the thrombin inhibition mechanism remains unclear, no previous studies have reported recent treatment outcomes in older patients producing thrombin-inhibiting substances, which can hinder clinical treatment. Therefore, we believe that the diagnosis and the treatment course of this case provide valuable information. Moreover, such case reports provide significant insights into the pathophysiology of bleeding complications associated with MM.

Real-world treatment patterns and outcomes of patients with advanced melanoma treated with nivolumab plus relatlimab

Abstract The use of programmed death-1 (PD-1) inhibitors has been a pivotal advancement in treating advanced melanoma, yet their efficacy is limited. The approval of relatlimab (RELA), a lymphocyte activation gene 3 protein (LAG-3) antibody, in combination with nivolumab (NIVO), a PD-1 inhibitor, marked a significant stride toward enhancing treatment efficacy for metastatic and unresectable stage 3 and 4 melanoma. This combination has been shown to synergistically improve antitumor activity and effector T-cell activity in the tumor microenvironment, despite limited data on real-world outcomes. Our retrospective review at a tertiary cancer center of patients with stage 3 and 4 melanoma treated with NIVO-RELA revealed an overall response rate (ORR) of 39%, with notable improvements in median PFS and ORR, especially in first-line treated patients. Our study highlights the superior efficacy of NIVO-RELA over previous reports, demonstrating its significant potential in the treatment landscape of advanced melanoma.

Alcohol consumption in cancer patients receiving psycho-oncologic care analysis of socio-demographic, health-related and cancer-related factors.

The carcinogenic effects of alcoholic beverages and the negative impact of alcohol consumption on cancer progression and treatment outcomes are well established in oncology research. Many cancer patients experience significant psychological distress, often manifesting as elevated levels of depression and anxiety. In the general population, alcohol consumption is commonly used as a coping mechanism for such distress. For cancer patients facing substantial psychological challenges, psycho-oncology care is available to help manage their symptoms and the overall impact of their condition. However, there is limited understanding of the alcohol consumption patterns in this particularly vulnerable group of patients, as well as the disease-related factors that may influence their drinking behavior. This study aims to examine the prevalence of potentially risky alcohol consumption in cancer patients receiving psycho-oncology care and to identify sociodemographic, health-related, and psychosocial factors associated with alcohol consumption after cancer diagnosis. By understanding drinking patterns and the factors associated with them, we aim to promote healthier behaviors and enhance treatment outcomes for cancer patients receiving psycho-oncology care. A consecutive sample of 1.225 patients from the psycho-oncology outpatient clinic of the University Medical Center Hamburg Eppendorf (UKE) was analyzed with regard to their alcohol consumption behavior using the Alcohol Use Disorders Identification Test-Consumption Items (AUDIT-C). Self-report questionnaires were employed to assess sociodemographic, health-related, and cancer-specific information. For statistical analysis, multiple linear regression was utilized. In the sample of cancer patients receiving psycho-oncology support one in six of both female and male patients showed risky alcohol drinking behavior (e.g. AUDIT-C above three for women and four for men). In the analysis (R-Square: 0.056) male gender (regression coefficient B 0.686, 95% CI: 0.453-0.919) and patientsreporting a higher physical health-related quality of life (SF8-PCS) (B 0.021, 95% CI: 0.011-0.032) were associated with higher levels of alcohol consumption, whereas having children (B -0.481, 95%CI: -0.700- -0.262) was associated with lower alcohol consumption. With regard to cancer type, a single-factor analysis of variance with gender as the centered covariate showed that patients with gastrointestinal cancer had had lower average consumption levels compared to the groups of patients with breast cancer, melanoma, genitourinary cancer, and lymphoma. Also, patients with sarcoma had lower average consumption levels than patients with lymphoma. The results allow to identify patient characteristics and cancer types associated with higher or lower alcohol consumption levels and higher likelihood of risky consumption behavior in this sample of cancer patients receiving psycho-oncological support. Cancer patients are particularly susceptible to the hazardous effects of alcohol consumption. The results of this study help to identify cancer patients at risk of worsening prognosis due to alcohol consumption and to develop intervention programs to minimize alcohol consumption in this group.

Attention-Enhanced Guided Multimodal and Semi-Supervised Networks for Visual Acuity (VA) Prediction after Anti-VEGF Therapy

The development of telemedicine technology has provided new avenues for the diagnosis and treatment of patients with DME, especially after anti-vascular endothelial growth factor (VEGF) therapy, and accurate prediction of patients’ visual acuity (VA) is important for optimizing follow-up treatment plans. However, current automated prediction methods often require human intervention and have poor interpretability, making it difficult to be widely applied in telemedicine scenarios. Therefore, an efficient, automated prediction model with good interpretability is urgently needed to improve the treatment outcomes of DME patients in telemedicine settings. In this study, we propose a multimodal algorithm based on a semi-supervised learning framework, which aims to combine optical coherence tomography (OCT) images and clinical data to automatically predict the VA values of patients after anti-VEGF treatment. Our approach first performs retinal segmentation of OCT images via a semi-supervised learning framework, which in turn extracts key biomarkers such as central retinal thickness (CST). Subsequently, these features are combined with the patient’s clinical data and fed into a multimodal learning algorithm for VA prediction. Our model performed well in the Asia Pacific Tele-Ophthalmology Society (APTOS) Big Data Competition, earning fifth place in the overall score and third place in VA prediction accuracy. Retinal segmentation achieved an accuracy of 99.03 ± 0.19% on the HZO dataset. This multimodal algorithmic framework is important in the context of telemedicine, especially for the treatment of DME patients.

Complete Skin Clearance is Associated with the Greatest Benefits to Health-Related Quality of Life and Perceived Symptoms for Patients with Psoriasis.

With newer biologics, the achievement of complete skin clearance has become an attainable treatment goal for patients with plaque psoriasis. We evaluate how improvements in Psoriasis Area and Severity Index (PASI) responses, particularly at incremental improvements approaching complete skin clearance (PASI 100), translate into improvements in health-related quality of life (HRQoL) and patient-perceived symptoms. Data from the BE RADIANT phase 3b trial (NCT03536884) and its open-label extension (OLE), pooled across all study visits and treatments over 16weeks (randomised patients) and 2years (patients entering the OLE), were analysed using mixed-effects logistic regression models. Proportions of patients achieving a Dermatology Life Quality Index (DLQI) of 0/1, DLQI item scores of 0, and Psoriasis Symptoms and Impacts Measure (P-SIM) item scores of 0 for itching, scaling, and skin pain at specific PASI improvement levels were estimated. Seven hundred andforty-three patients were randomised to treatment; 654 entered the OLE. Using 16-week pooled data, there were incremental improvements in the proportions of patients estimated by our model to achieve DLQI 0/1 with PASI 100 compared with 95% (PASI = 95%) and 90% (PASI = 90%) improvements in PASI (93.0%, 89.3%, and 83.8% achieving DLQI 0/1, respectively). Estimated proportions achieving DLQI item scores of 0 had the greatest increases at higher PASI improvement levels for Items 1 (itchy, sore, painful, or stinging skin), 2 (embarrassment), and 4 (choice of clothing). Estimated proportions of patients achieving P-SIM = 0 were also higher for PASI 100 (itching: 61.7%; scaling: 82.2%; skin pain: 96.9%) than for PASI = 95% (50.8%; 72.3%; 95.7%) and PASI = 90% (39.8%; 59.5%; 94.0%). Similar benefits of incremental PASI improvements were estimated using 2-year data. Complete skin clearance translated into the greatest benefits to HRQoL and patient-perceived symptoms, over and above skin clearance between 90% and 100%, highlighting the importance of targeting PASI 100 as a treatment outcome for patients with psoriasis. NCT03536884. Complete skin clearance is associated with the greatest benefits to health-related quality of life and perceived symptoms for patients with psoriasis: KeyResults and Conclusions (MP4 72828 kb).

Pharmacokinetics-pharmacodynamics of first-line antitubercular drugs: a comparative study in tuberculosis patients with and without concomitant diabetes mellitus.

To observe the variability in the plasma concentrations and pharmacokinetic-pharmacodynamic (PK-PD) profiles of first-line antitubercular drugs in pulmonary tuberculosis (TB) patients with and without diabetes mellitus (DM). Newly diagnosed pulmonary TB patients aged 18-60years with or without DM were included in the study. Group I (n = 20) included patients with TB, whereas group II (n = 20) included patients withboth TB and DM. After 2 weeks of therapy, plasma concentrations and other PK-PD parameters were determined. Improvements in clinical features, X-ray findings, sputum conversion, and adverse drug reactions (ADRs) were assessed after 2 months of therapy. Isoniazid displayed non-significantly higher plasma concentrations in diabetic patients, along with a significantly (P < 0.05) longer elimination half-life (t1/2). Rifampicin plasma concentrations at 4, 8, and 12 h were significantly (P < 0.05) lower, and it displayed significantly (P < 0.05) lower area underthe curve (AUC0-12 and AUC0-∞), shorter t1/2, higher clearance (Cl), and a lower AUC0-∞/MIC ratio in diabetic patients. Pyrazinamide and ethambutol showed non-significantly higher plasma concentrations, AUC0-12, AUC0-∞, and t1/2 in diabetic patients. The improvements in clinical features, X-ray findings, sputum conversion, and ADRs were comparable in both groups. The presence of DM in TB patients affects the PK-PD parameters of isoniazid, rifampicin, pyrazinamide, and ethambutol variably in the Indian population. Studies with a larger number of patients are required to further elucidate the role of DM on the PK-PD profile of first-line antitubercular drugs and treatment outcomes in TB patients with concomitant DM. CTRI/2021/08/035578 dated 11/08/2021.