Efficacy Of Different Treatments Research Articles

RADT-01. PRE-OPERATIVE SINGLE FRACTION VERSUS FRACTIONATED STEREOTACTIC RADIOTHERAPY: A SINGLE-INSTITUTION ANALYSIS OF 299 RESECTED METASTASES

Abstract The treatment standard for patients with large or symptomatic brain metastases and limited intracranial disease is surgical resection followed by post-operative (post-op) stereotactic radiosurgery (SRS). The multicenter PROPS-BM cohort showed how pre-operative (pre-op) SRS may lead to a reduced incidence of radiation necrosis (RN), local failure (LF), and meningeal disease (MD) compared to historical controls. Fractionated treatments can deliver a higher biological effective dose and may reduce the incidence of LF and MD. We hypothesize that pre-op fractionated stereotactic radiation therapy (FSRT) will reduce the incidence rate of RN, MD, and LF when compared to patients who receive pre-op SRS. Patients who had surgical resection and pre-operative radiation to at least one brain metastasis at a single institution were retrospectively analyzed. Outcomes were evaluated on a per-lesion basis. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. 260 patients with 299 resected brain metastases were eligible for analysis. 64 metastases received SRS and 235 metastases received FSRT. 38 patients had multiple metastases resected pre-operatively. The median gross tumor volume was 4 ccs for SRS and 10 ccs for FSRT (p<0.001). Overall, 4 (6.3%) SRS and 6 (2.6%) FSRT patients experienced LF. 4 (6%) SRS and 21 (8.9%) FSRT patients experienced Grade 2 or higher RN. 3 (4.7%) SRS and 11 (4.7%) FSRT patients were diagnosed with MD. 14% of both SRS and FSRT patients experienced the composite endpoint. There were no statistically significant differences in outcome between these two treatment groups. In our study, pre-op SRS and FSRT both appear to be safe and effective options to treat resectable brain metastases. It is important to prospectively compare pre-op SRS and FSRT in matched cohorts to assess any differences in treatment efficacy and toxicity.

Cachexia and efficiency of trifluridine/thymidine phosphorylase inhibitor + bevacizumab in metastatic colorectal cancer

In later-line treatment of metastatic colorectal cancer (mCRC), there may be large differences in treatment efficacy depending on cancer cachexia. Recently, the cachexia index (CXI), which was calculated from the skeletal muscle mass index (SMI), serum albumin concentration, and neutrophil-to-lymphocyte ratio, was developed to evaluate cancer cachexia. We retrospectively examined the CXI of 80 patients who were treated with trifluridine/thymidine phosphorylase inhibitor (FTD/TPI) + bevacizumab (Bmab) therapy as a later-line treatment for mCRC, and assessed the impact of cancer cachexia on chemotherapeutic efficacy using CXI. Progression-free and overall survival rates were significantly worse in the low CXI group than in the high CXI group, although there were no marked differences in tumor factors, such as the number of metastatic organs or gene mutations, between the two groups. As the cross-sectional area of the iliopsoas muscle was significantly associated with that of the skeletal muscle, the accuracy of the CXI based on the psoas mass index (P-CXI), which is easier to calculate than the SMI, in predicting treatment outcomes was equivalent to that of the CXI based on the SMI (S-CXI). Cancer cachexia is an important factor related to treatment efficacy in later-line treatments, such as FTD/TPI + Bmab therapy.

Simulation-free prediction of atrial fibrillation inducibility with the fibrotic kernel signature

Computational models of atrial fibrillation (AF) can help improve success rates of interventions, such as ablation. However, evaluating the efficacy of different treatments requires performing multiple costly simulations by pacing at different points and checking whether AF has been induced or not, hindering the clinical application of these models. In this work, we propose a classification method that can predict AF inducibility in patient-specific cardiac models without running additional simulations. Our methodology does not require re-training when changing atrial anatomy or fibrotic patterns. To achieve this, we develop a set of features given by a variant of the heat kernel signature that incorporates fibrotic pattern information and fiber orientations: the fibrotic kernel signature (FKS). The FKS is faster to compute than a single AF simulation, and when paired with machine learning classifiers, it can predict AF inducibility in the entire domain. To learn the relationship between the FKS and AF inducibility, we performed 2371 AF simulations comprising 6 different anatomies and various fibrotic patterns, which we split into training and a testing set. We obtain a median F1 score of 85.2% in test set and we can predict the overall inducibility with a mean absolute error of 2.76 percent points, which is lower than alternative methods. We think our method can significantly speed-up the calculations of AF inducibility, which is crucial to optimize therapies for AF within clinical timelines. An example of the FKS for an open source model is provided in https://github.com/tbanduc/FKS_AtrialModel_Ferrer.git.

Sex-Specific Cardiovascular Risk Factors and Treatment in Females With T2DM and CVD: Developments and Knowledge Gaps

Abstract Purpose There are large disparities in the impact of diabetes on cardiovascular disease (CVD) risk and outcomes by sex and gender. Achieving health equity requires understanding risks and medication efficacy in female patients, especially now, as novel pharmacologic treatments are transforming the diabetes and CVD treatment landscape. This review examines 2 bodies of research that can inform sex differences in CVD in patients with diabetes: female-specific risk factors for CVD and sex-related limitations of clinical trial research in evaluating novel diabetes and CVD treatments. Methods Two literature searches were performed using Ovid Medline(R) All. The first retrieved manuscripts covering sex and gender differences related to CVD risk and therapies and diabetes. The second focused on randomized controlled trial data on sex/gender differences and GLP-1/SGLT-2/DPP-4 drugs. Results Female-specific risk factors for CVD include early menarche, premature or early menopause, irregular cycles and polycystic ovary syndrome; pregnancy; adverse pregnancy outcomes; history of breast cancer; and autoimmune diseases. Clinical trials of novel pharmacological treatments for diabetes and CVD have undersampled female populations, and clinical characteristics of male and female participants have differed significantly. Thus, evidence to evaluate potential sex differences in treatment efficacy and side effects has been lacking. Conclusion To improve health of female patients with diabetes, sex-specific cardiovascular risk factors should be taken into account in screening and treatment decisions. Further, studies of cardiovascular and diabetes medications must ensure adequate representation by sex and report participant characteristics and outcomes by sex.

Development and validation of a novel immune‒metabolic-Based classifier for hepatocellular carcinoma

The heterogeneity of immune cells and metabolic pathways in hepatocellular carcinoma (HCC) patients has not been fully elucidated, leading to diverse clinical outcomes. Accurately distinguishing different HCC subtypes and recommending appropriate treatments is are highly important. In this study, we conducted a comprehensive analysis of 28 immune cells and 85 metabolic pathways in the TCGA-LIHC and GSE14520 datasets. Metabolism-related first principal component (MRPC1) and cytotoxic T lymphocyte (CTL) infiltration were used to assess the metabolic and immune infiltration levels of HCC patients, respectively. These two quantifiable indicators were then used to construct an immune‒metabolic classifier, which categorized HCC patients into three distinct groups. The potential biological mechanisms were explored through multiomics analysis, revealing that group S1 exhibited high metabolic activity and a high level of immune infiltration, that group S2 presented a low level of immune infiltration, and that group S3 presented low metabolic activity. This new immune‒metabolic classifier was well validated in a pancancer cohort of 9296 patients. The efficacy of multiple treatment approaches was assessed in relation to different immune‒metabolic groups, indicating that group S1 patients may benefit from immunotherapy, that group S2 patients are suitable for transcatheter arterial chemoembolization (TACE), and that group S3 patients are appropriate candidates for tyrosine kinase inhibitors. In conclusion, this immune‒metabolic classifier is anticipated to address the differences in treatment efficacy among HCC patients due to the heterogeneity of the tumor microenvironment, and to help refine the individualized treatment choices for clinical patients.

Why Have We Not Been Able to Demonstrate Reduced Mortality in Patients With HFmrEF/HFpEF?

No randomized controlled trial has yet demonstrated a statistically significant reduction in mortality in patients with heart failure and mildly reduced ejection (HFmrEF) or heart failure and preserved ejection fraction (HFpEF), in contrast to the benefits observed in heart failure with reduced ejection fraction (HFrEF). However, this probably reflects the statistical power of trials to date to show an effect on mortality rather than mechanistic differences between HFmEF/HFpEF and HFrEF or differences in treatment efficacy. Compared to patients with HFrEF, those with HFmrEF/HFpEF have lower mortality rates and a smaller proportion of potentially modifiable cardiovascular deaths (as opposed to unmodifiable noncardiovascular deaths). In addition, some causes of cardiovascular deaths may not be reduced by treatments for HF. Therefore, the low rate of potentially modifiable deaths in patients with HFmrEF/HFpEF, compared with HFrEF, has made it challenging to demonstrate a reduction in death (or cardiovascular death) in trials to date.

Which intervention is optimal to control blood glucose and improve physical performance in the elderly living with type 2 diabetes mellitus? A network meta-analysis.

This study aimed to find the optimal intervention available to both control blood glucose and improve physical function in the geriatric population with T2DM. A systemic review and network meta-analysis (NMA) was conducted to assess and rank the comparative efficacy of different interventions on glycosylated hemoglobin A1c (HbAc1), fasting blood glucose (FBG), muscle mass, grip strength, gait speed, lower body muscle strength, and dynamic balance. A total of eight databases were searched for eligible randomized controlled trials (RCTs) that the elderly aged more than 60 years or with mean age ≥ 55 years, the minimal duration of the RCT intervention was 6 weeks, and those lacking data about glycemic level and at least one indicator of physical performance were excluded. The Cochrane risk of bias tool was used to assess the bias of each study included. Bayesian NMA was performed as the main results, the Bayesian meta regression and the frequentist NMA as sensitivity analysis. Of the 2266 literature retrieved, 27 RCTs with a total of 2289 older adults were included. Health management provided by health workers exerts beneficial effects that is superior to other interventions at achieving glycemic control, but less marked improvement in physical performance. Exercise combined with cognitive training showed more pronounced improvement in muscle strength, gait speed, and dynamic balance, but ranked behind in decreasing the HbAc1 and FBG. Personalized health management combined with physical and cognitive training might be the optimal intervention to both accomplish glycemic control and improvement of physical performance. Further RCTs are needed to validate and assess the confidence of our results from this NMA.

Efficacy of eHealth Versus In-Person Cognitive Behavioral Therapy for Insomnia: Systematic Review and Meta-Analysis of Equivalence.

Insomnia is a prevalent condition with significant health, societal, and economic impacts. Cognitive behavioral therapy for insomnia (CBTI) is recommended as the first-line treatment. With limited accessibility to in-person-delivered CBTI (ipCBTI), electronically delivered eHealth CBTI (eCBTI), ranging from telephone- and videoconference-delivered interventions to fully automated web-based programs and mobile apps, has emerged as an alternative. However, the relative efficacy of eCBTI compared to ipCBTI has not been conclusively determined. This study aims to test the comparability of eCBTI and ipCBTI through a systematic review and meta-analysis of equivalence based on randomized controlled trials directly comparing the 2 delivery formats. A comprehensive search across multiple databases was conducted, leading to the identification and analysis of 15 unique randomized head-to-head comparisons of ipCBTI and eCBTI. Data on sleep and nonsleep outcomes were extracted and subjected to both conventional meta-analytical methods and equivalence testing based on predetermined equivalence margins derived from previously suggested minimal important differences. Supplementary Bayesian analyses were conducted to determine the strength of the available evidence. The meta-analysis included 15 studies with a total of 1083 participants. Conventional comparisons generally favored ipCBTI. However, the effect sizes were small, and the 2 delivery formats were statistically significantly equivalent (P<.05) for most sleep and nonsleep outcomes. Additional within-group analyses showed that both formats led to statistically significant improvements (P<.05) in insomnia severity; sleep quality; and secondary outcomes such as fatigue, anxiety, and depression. Heterogeneity analyses highlighted the role of treatment duration and dropout rates as potential moderators of the differences in treatment efficacy. eCBTI and ipCBTI were found to be statistically significantly equivalent for treating insomnia for most examined outcomes, indicating eCBTI as a clinically relevant alternative to ipCBTI. This supports the expansion of eCBTI as a viable option to increase accessibility to effective insomnia treatment. Nonetheless, further research is needed to address the limitations noted, including the high risk of bias in some studies and the potential impact of treatment duration and dropout rates on efficacy. PROSPERO CRD42023390811; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=390811.

Efficacy and feasibility analysis of compound fluocinolone acetonide cream combined with guaiazulene in the treatment of neurodermatitis.

To evaluate the effectiveness and feasibility of combined treatment with compound fluocinolone acetonide cream and guaiazulene in patients with neurodermatitis. A prospective study was conducted on 92 outpatient patients diagnosed with neurodermatitis at our dermatology department from January 2022 to December 2023. Using a random number table, these patients were evenly divided into a control group and an experimental group, with 46 individuals in each group. The control group received treatment with compound fluocinolone acetonide alone, while the experimental group additionally received oral guaiazulene tablets. Clinical symptom and sign scores, Visual Analog Scale (VAS) scores, skin lesion itching scores, comprehensive efficacy, treatment onset time, adverse reactions, and quality of life were monitored, recorded, and compared. In the 2-week treatment period, patients in the experimental group showed significant improvement in skin symptoms and signs, with scores significantly lower than those in the control group (P < 0.05). After treatment, VAS and skin lesion itching scores in the experimental group were significantly reduced (P < 0.05), demonstrating a more pronounced therapeutic advantage compared to the control group (P < 0.05). Although the effective rate in the experimental group was as high as 86.96%, there was no significant advantage compared to the control group, and the difference in treatment efficacy was not significant (P > 0.05). The treatment onset time in the experimental group was significantly shorter than that in the control group (P < 0.05), and the incidence of adverse reactions was lower (P < 0.05). The quality of life in the experimental group improved significantly after treatment, with DLQI scores lower than those in the control group (P < 0.05). Combined treatment with compound fluocinolone acetonide cream and guaiazulene demonstrates excellent efficacy and feasibility in the management of neurodermatitis. Compared to standard treatment alone, it yields superior clinical outcomes.

Efficacy of surgical treatments for the management of solitary rectal ulcer syndrome: a network meta-analysis.

Solitary rectal ulcer syndrome (SRUS) is a benign and poorly understood disorder with complex management. Typical symptoms include straining during defaecation, rectal bleeding, tenesmus, mucoid secretion, anal pain and a sense of incomplete evacuation. Diagnosis is based on characteristic clinical symptoms and endoscopic/histological findings. Several treatments have been reported in the literature with variable ulcer healing rates. This study aimed to evaluate the efficacy of different treatments for SRUS. A systematic review and network meta-analysis were performed according to the PRISMA guidelines. Studies in English, French and Spanish languages were included. Papers written in other languages were excluded. Other exclusion criteria were reviews, case reports or clinical series enrolling less than five patients, study duplications, no clinical data of interest and no article available. A systematic literature search was conducted from January 2000 to March 2024 using the following databases: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus. The biases of the studies were assessed using the Newcastle-Ottawa scale or the Jadad scale when appropriate. Types of treatment and their efficacy for the cure of SRUS were collected and critically assessed. The study's primary outcome was to estimate the rate of patients with ulcer healing. A total of 22 studies with 911 patients (men 361, women 550) diagnosed with SRUS were analysed in the final meta-analysis. The pooled effect estimates of treatment efficacy revealed that surgery showed the highest ulcer healing rate (70.5%; 95% CI 0.57-0.83). Surgery was superior in the cure of ulcers with respect to medical therapies and biofeedback (OR 0.09 and OR 0.14). Solitary rectal ulcer syndrome is a challenging clinical entity to manage. Proficient results have been reported with the surgical approach, suggesting its positive role in cases refractory to medical and biofeedback therapy. Further studies in homogeneous populations are required to evaluate the efficacy of surgery in this setting. (PROSPERO registration number CRD42022331422).

The Role of Different Medical Therapies in the Management of Adenomyosis: A Systematic Review and Meta-Analysis.

Background/Objectives: Adenomyosis is a benign condition characterized by the presence of endometrial tissue within the myometrium. Despite surgery being a valuable approach, medical options are considered as the first-line approach and have been investigated in the treatment of adenomyosis, although strong evidence in favor of these is still lacking. This study aims to gather all available data and determine the effectiveness of the aforementioned medical options in patients with associated pain and not currently seeking pregnancy, both in comparison to placebo and to one another. Methods: For this study, PubMed and EMBASE were used as data sources, searched up to January 2024. A systematic review and meta-analysis were performed in accordance to guidelines from the Cochrane Collaboration. The primary outcomes investigated were changes in dysmenorrhea, quantified by means of VAS scores, HMB in terms of number of bleeding days, and changes in uterine volume determined at ultrasound. Twelve eligible studies were selected. Results: The results highlighted that dienogest yields a reduction in dysmenorrhea that is significantly superior to that of the rest of the medical treatments investigated (p-value of <0.0002). On the other hand, GnRH agonists seem to play a more prominent role in reducing uterine volume (p-value of 0.003). While it was not possible to determine which medical treatment better decreased the number of bleeding days, it was observed that COC performed significantly worse than the other treatments studied (p-value of 0.02). Conclusions: While this meta-analysis provides valuable insights in the comparative efficacy of different treatments, the paucity of relevant studies on the topic might impact the reliability of some of the conclusions drawn.

Comparison of efficacies of different treatments for nontuberculous mycobacterial pulmonary disease in Anhui Province, China.

Although nontuberculous mycobacterial (NTM) infection is a common cause of pulmonary disease worldwide, few studies have focused on epidemiological and therapeutic factors related to NTM cases in Anhui Province, China. This retrospective study aimed to identify aetiological and clinical factors, and treatment outcomes of patients with NTM pulmonary disease (NTMPD) in Anhui. Retrospective clinical data obtained from medical records of NTMPD patients seeking care at Anhui Chest Hospital from July 2019 to June 2022 were analyzed. Treatment outcomes were compared between two patient groups: one receiving a standardised NTM treatment regimen and the other receiving precision treatment regimens. Genotypic analysis of 672 clinical NTMPD-associated isolates revealed that most were Mycobacterium intracellulare, while drug-susceptibility test results demonstrated diverse antibiotic resistance profiles for these isolates. Cough was the most common symptom for 101 NTMPD patients. After patients of both groups received treatment, symptoms improved, sputum culture conversion was observed for some patients, imaging findings stabilised; however, no statistically significant intergroup differences in treatment outcomes were found. In this study, M. intracellulare was the predominant NTM species identified in isolates obtained from NTMPD patients. Drug resistance profiles of our patient isolates were complex, highlighting the need for administration of timely, more effective, standardised treatments for patients with NTMPD in Anhui Province, China.

Abstract PO5-03-07: Impact of age and stage on pathologic complete response rates in Black vs White patients with triple negative breast cancer

Abstract Background Triple-negative breast cancer (TNBC) accounts for approximately 10-15% of breast cancers. Women with TNBC have worse survival outcomes, increased rates of relapse, and distant metastasis as compared to women with non-TNBC. Regardless of subtype, Black women have worse breast cancer outcomes than White women. Early stage treatment of TNBC has focused on neoadjuvant therapy (NACT) with a goal of achieving a pathologic complete response (pCR), which is associated with longer event-free survival and overall survival in TNBC patients. NACT with pembrolizumab was presented at the San Antonio Breast Cancer Symposium in December 2019 and FDA approved in July 2021. The Keynote-522 Trial found that patients who received NACT + pembrolizumab were more likely to achieve pCR than women who received NACT + placebo, regardless of stage. The KEYNOTE-522 trial did not examine race or age differences in treatment efficacy. Since TNBC disproportionately affects younger women and Black women, optimizing pCR rates in these groups is essential. Our objective is to examine racial differences in pCR rates by cancer stage and age among patients with TNBC who completed NACT/pembrolizumab. Methods Patient records from Ochsner Health, a regional network, were reviewed for those with early stage TNBC who had completed treatment with NACT/pembrolizumab from January 2020 to January 2022. Exclusion criteria included no surgical treatment for TNBC, unknown receptor status, and age &amp;lt; 18 years-old. Chi-square and Fisher’s Exact tests were used to examine the relationship between race and pCR stratified by stage at diagnosis and age. Risk ratios and 95% confidence intervals were also estimated to examine the strength of these relationships. Results We identified 92 patients with TNBC who completed treatment with NACT/pembrolizumab and underwent surgery. 52 patients (56%) were Black and 40 patients (43%) were White. 53.85% of Black patients had pCR and 67.50% of White patients experienced pCR (p=0.19). Among patients with stage III disease, only 37.50% of Black patients experienced pCR compared to 69.23% of White patients (p=0.09). Notably, Black patients were 46% less likely to experience pCR than = White patients (RR: 0.54, 95% CI: 0.28-1.02) in the stage III group. Among patients less than 50 years of age, 41.18% of Black patients experienced pCR compared to 84.21% of White patients (p=0.01), where younger Black patients were 51% less likely to experience pCR than younger White patients (RR: 0.49, 95% CI: 0.27-0.89) There were no observed racial differences in pCR rates for stage I/II patients (p=1.00) or patients aged 50 years or older (p=0.64). Discussion These data demonstrate that Black women are at a pCR rate disadvantage receiving NACT/pembrolizumab. This is primarily driven by advanced stage and young age. Black patients with stage III cancers had significantly lower pCR rates than their White counterparts after having received the same treatment. Additionally, young patients who are Black have significantly lower pCR rates. For older patients and those with stage I/II disease, there was no statistically significant difference in pCR rates between Black vs White race. Conclusion While NACT/pembrolizumab offers overall increased rates of pCR, Black women, especially those who are young or with more advanced disease at presentation, still have worse outcomes. Further research is needed to determine underlying predictors or alternative treatments to benefit these populations. Table 1 Distribution of Pathological Complete Response Following NACT/pembrolizumab treatment (Nf91) Table 2 Crude Risk Ratios for the Relationship between Race and Pathological Complete Response by Age and Stage (Nf92) Citation Format: Melanie Sheen, Caitlin Taylor, Rabia Cattie, Melyssa Bratton, Meredith Lakey, Victoria Chung, Erin Biggs. Impact of age and stage on pathologic complete response rates in Black vs White patients with triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-03-07.

Abstract PO1-15-06: Serum thymidine kinase activity as a “real-time” clinical biomarker of tumor response to CDK4/6 inhibition in hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer

Abstract Background: CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) are standard first-line (1L) treatment for hormone receptor positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC). Despite general improvements in long-term outcome, not all patients benefit equally from these drugs. The average duration of 1L CDK4/6i therapy is ~2 years. However, 10-15% of patients will progress within 6 months of therapy initiation, while others will derive durable clinical benefit of years. Differences in treatment efficacy cannot be easily explained by clinical-pathological features. No predictive biomarkers are currently available to determine tumor sensitivity to CDK4/6i. There is an unmet need for a complementary diagnostic to identify patients that will or will not respond to these treatments in order to better inform therapy management. Thymidine kinase (TK) is an E2F-regulated enzyme that plays a key role in DNA replication during cell division. The expression and activity of TK is strongly linked to the cell cycle. TK is first expressed in late G1, peaks during S-phase, and then is degraded during mitosis. Because of the restricted expression of TK (only during S phase of the cell cycle) combined with the mechanism of action of CDK4/6i, the measurement of TK activity (TKa) may serve as an ideal pharmacodynamic biomarker to assess a tumor’s response to CDK4/6i-based therapy. DiviTum® TKa is an FDA cleared assay that can quantitate TKa from human serum (sTKa) and is intended to be used as a disease progression monitoring tool for patients with HR+, HER2- MBC. TK IMPACT is a prospective, single arm trial designed to assess the impact of incorporation of DiviTum® TKa on the physician’s decision regarding subsequent timing of routine disease monitoring modalities in patients with advanced HR+, HER2- MBC receiving 1L ET plus CDK 4/6i (NCT04968964). As a part of this ongoing study, DiviTum® TKa values are serially assessed relative to imaging findings and other circulating tumor biomarkers, such as CA15-3 and ctDNA. The primary endpoint is any physician-reported intended change in imaging testing interval post TKa by study cohort, within the first 48-week period of study participation, assessments for which are ongoing. Here we report real-world data and examples of the clinical utility of sTKa as a companion diagnostic from patients treated at Washington University Siteman Cancer Center, St. Louis, MO. Methods: Patients with HR+, HER2- MBC receiving 1L ET + any FDA-approved CDK 4/6i (palbociclib, ribociclib, or abemaciclib) had blood serum samples collected at baseline, weeks 2, 4, 6, 8, every 4 weeks up to week 24, and then every 12 weeks thereafter until disease progression. Samples were analyzed for TKa levels in real-time using the DiviTum® TKa assay. Optional repeat TKa within 2-4 wks (+/- 3 days) is permitted in case of rising TKa. Other standard monitoring assessments were carried out according to institutional guidelines and/or treating clinician discretion. Results: Pre-treatment and early on-therapy TKa levels predicted response to CDK4/6i therapy more accurately than a patient’s clinical characteristics. Rising TKa levels also identified patients with clinically occult disease progression ahead of imaging, and in some cases where radiographic interpretation and serum tumor markers such as CA15-3 were ambiguous. Measurement of TKa levels following CDK4/6i dose reduction was able to confirm continued optimal therapy response at the lower dose. A rise in TKa levels aligned with the re-emergence of ESR1 mutation as identified by ctDNA in one patient and may herald molecular progression. Conclusion: sTKa was able to predict tumor sensitivity and resistance (both intrinsic and acquired) to CDK4/6i + ET therapy in patients with HR+, HER2- MBC. We believe these findings help support the role of sTKa as a non-invasive pharmacodynamic biomarker that can assess in real-time a tumor’s response to CDK4/6i based therapy. Citation Format: Nusayba Bagegni, Amy Williams, Isabella Grigsby, Mattias Bergqvist, Katherine Clifton, Cynthia Ma. Serum thymidine kinase activity as a “real-time” clinical biomarker of tumor response to CDK4/6 inhibition in hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-06.

In vitro Evaluation of Botanical Extracts against Mycelial Growth of Alternaria solani

An experiment was conducted at the laboratory of the Department of Plant Pathology, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, Uttar Pradesh. To test the efficacy of different treatments viz., Neem (Azadirachta indica), Onion (Allium cepa), Garlic (Allium sativum), Castor (Ricinus communis), Amaltas (Cassia fistula), Henna (lawsonia inermis), Madar (Calotropis gigantea) against Alternaria solani under in vitro condition. Botanicals were tested through the poisoned food technique at 5% and 10 % concentrations and 168 hours of incubation. The Minimum radial growth of observed in Neem (Azadirachta indica) seed kernel extract @ 5% (14.8mm) followed by Henna (lawsonia inermis) leaf extract @ 10% (43.36mm), Amaltas (Cassia fistula) leaf extract @ 10% (67.13mm), Castor (Ricinus communis) leaf extract @ 10% (67.6mm), Madar (Calotropis gigantea) leaf extract @ 10% (69.6mm), Onion (Allium cepa) extract @ 10 % (70.8mm), Garlic (Allium sativum) extract @ 10 % (72.2mm) as compared to Control (89.4mm) untreated check.

Comparative efficacy of different interventions on executive function in adolescents with internet use disorder

BackgroundThe formation and relapse of Internet use disorder (IUD) are related to the decline in executive function. Previous studies have indicated that exercise intervention and high-definition transcranial direct current stimulation (HD-tDCS) can improve the cognitive abilities of adolescents with IUD. However, the combined intervention's impact on executive function in these adolescents remains unclear. Therefore, this study aims to explore the effects and differences of multimodal exercise, HD-tDCS intervention, and combined intervention on the executive function of adolescents with IUD. MethodsForty-eight adolescents with IUD were randomly assigned to the multimodal exercise group, HD-tDCS intervention group, combined intervention group, and control group. The intervention groups received 4 weeks of moderate-intensity multimodal exercise, HD-tDCS intervention (2 mA, 20min/session, 3 times/week), or combined multimodal exercise with HD-tDCS intervention. The control group received conventional educational learning. Executive function measurements were taken before intervention, after intervention, and 2 weeks post-intervention. ResultsCompared to pre-intervention, different interventions effectively improved the behavioral performance of adolescents with IUD in executive function tasks. In comparison to single interventions, the combined intervention significantly outperformed multimodal exercise and HD-tDCS intervention in influencing the executive function (especially inhibitory control and working memory) in adolescents with IUD. ConclusionCombined multimodal exercise with HD-tDCS intervention proves to be an effective means of enhancing executive function in adolescents with IUD, particularly contributing to the improvement of explicit behavioral performance related to executive function.

Docetaxel, cyclophosphamide, and epirubicin: application of PBPK modeling to gain new insights for drug-drug interactions.

The new adjuvant chemotherapy of docetaxel, epirubicin, and cyclophosphamide has been recommended for treating breast cancer. It is necessary to investigate the potential drug-drug Interactions (DDIs) since they have a narrow therapeutic window in which slight differences in exposure might result in significant differences in treatment efficacy and tolerability. To guide clinical rational drug use, this study aimed to evaluate the DDI potentials of docetaxel, cyclophosphamide, and epirubicin in cancer patients using physiologically based pharmacokinetic (PBPK) models. The GastroPlus™ was used to develop the PBPK models, which were refined and validated with observed data. The established PBPK models accurately described the pharmacokinetics (PKs) of three drugs in cancer patients, and the predicted-to-observed ratios of all the PK parameters met the acceptance criterion. The PBPK model predicted no significant changes in plasma concentrations of these drugs during co-administration, which was consistent with the observed clinical phenomenon. Besides, the verified PBPK models were then used to predict the effect of other Cytochrome P450 3A4 (CYP3A4) inhibitors/inducers on these drug exposures. In the DDI simulation, strong CYP3A4 modulators changed the exposure of three drugs by 0.71-1.61 fold. Therefore, patients receiving these drugs in combination with strong CYP3A4 inhibitors should be monitored regularly to prevent adverse reactions. Furthermore, co-administration of docetaxel, cyclophosphamide, or epirubicin with strong CYP3A4 inducers should be avoided. In conclusion, the PBPK models can be used to further investigate the DDI potential of each drug and to develop dosage recommendations for concurrent usage by additional perpetrators or victims.

Efficacy of Different Treatment Approaches (Insulin and Metformin) in Women with Gestational Diabetes Mellitus (GDM)

Background and Purpose: The pharmacotherapy options in patients with gestational diabetes mellitus (GDM) are insulin or oral antihyperglycemic agents. Insulin is the preferred medication for treating hyperglycemia, but in recent years, metformin has been increasingly used in the treatment of GDM. Aim: The aim is to assess the efficacy of different treatments (insulin and metformin) in women with GDM. Methods: Screening for GDM was performed in 2422 pregnant women and revealed GDM in 119 women [75 g oral glucose tolerance test (OGTT) was performed at 24–28 weeks of gestation]. All patients started treatment at 24–29 weeks of gestation. The patients were divided into two groups (Gr.): Gr. 1 had 68 patients treated with diet and insulin therapy. Gr. 2 had 51 patients treated with diet and metformin. Results: In the 2nd trimester, HbA1c (%) levels for Gr. 1 and Gr. 2 were 6.7 (0.05) and 6.4 (0.6), respectively. By term, HbA1c levels statistically decreased in both groups, but we did not find a statistical difference between the groups. Women from Gr. 2 gained less weight compared to Gr. 1 (1.89 ± 3.88 vs. 4.53 ± 3.67 kg; P = 0.003). In Gr. 1, the percentage of preeclampsia was 2.9%, and in Gr. 2, 3.9% (P = 0.7773, OR – 1.33). We did not find a statistical difference between the groups. The incidence of preterm delivery before 37 weeks of gestation in Gr. 1 was lower than in Gr. 2 (P = 0.7311, OR – 1.33), and we also did not find a statistical difference between the groups. Perinatal mortality was observed in Gr. 1 – 1.4% and in Gr. 2 – 1.9% (P = 0.8402, OR – 1.33). In both groups, we observed a high percentage of cesarean section (Gr. 1 – 32.3% and Gr. 2 – 29.4% (P = 0.7651, OR -1.0909), but we did not find a statistical difference between the groups. In both groups, the percentage of macrosomia was high, despite good glycemic control maintained through pregnancies: 20.0% and 23.0% for Gr. 1 and Gr. 2, respectively (P = 0.9236, OR – 1.0256), and again no statistical difference was found between the groups. Percent of neonatal hypoglycemia was lower in Gr. 2 (1.9%) than in Gr. 1 (4.41%) (P = 0.9236, OR – 1.0256). Percent of respiratory distress syndrome was 2.94% and 3.92% for Gr. 1 and Gr. 2, respectively (P = 0.9694, OR – 0.9893), with no statistical difference between the groups. Conclusion: We did not find differences between patients treated with diet and insulin therapy and patients treated with diet and metformin. The percentage of preeclampsia, preterm delivery, macrosomia, and perinatal death were similar in both groups; only maternal weight gain was lower in the metformin group.

A Bayesian Network Meta-Analysis of the Effect of Targeted Therapies on the Total Length of Hospital Stay in Children with Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare potentially life-threatening hypersensitivity disorders characterized by widespread skin and mucosal involvement. However, there is no standardized evidence-based treatment to reduce the complications of SJS/TEN. This article aims to compare the efficacy of different treatments for pediatric SJS/TEN in terms of length of hospital stay (LOS) using a Bayesian network meta-analysis (NMA). A Bayesian NMA is used to compare and combine evidence from multiple studies and allows clinicians to estimate the relative effectiveness of different treatments/interventions while accounting for heterogeneity in the available evidence. Methods: We conducted a comprehensive electronic database search for studies compatible with our inclusion criteria. Six studies with 103 patients were included in the NMA; of them, 37 patients were treated with intravenous immunoglobulin (IVIG), 37 with systemic corticosteroids (CS), 23 with IVIG + CS, and 3 with Etanercept (ET) + CS. Patients with a median age of 10 years were included in the study. Results: CS had the highest probability of being the most optimal treatment for SJS/TEN in terms of shorter LOS based on the Surface Under the Cumulative Ranking curve levels, and CS + IVIG was associated with a statistically nonsignificant trend toward shorter LOS than IVIG alone. Remarkably, none of the treatments showed a significant benefit over the other interventions in terms of LOS. Conclusion: Current evidence suggests that coadministration of CS and IVIG may be associated with a shorter LOS than IVIG alone. Further research with larger randomized controlled trials is needed to reach a definitive conclusion about the efficacy of specific therapy on LOS in pediatric SJS/TEN and to establish more definitive treatment guidelines.

External treatment of traditional Chinese medicine for cancer pain: A systematic review and network meta-analysis.

Cancer pain is one of the most intolerable and frightening symptoms of cancer patients. However, the clinical effect of the three-step analgesic ladder method (TSAL) is not satisfactory. The combination of external treatment of traditional Chinese medicine (TCM) can improve the clinical effect. This study used network meta-analysis to compare the effects of different external treatment methods of TCM combined with TSAL on cancer pain. Databases searched by our team included Google Scholar, Web of Science, Scopus, Embase, PubMed, and Cochrane Library. Randomized controlled trials related to the external treatment of TCM combined with TSAL for cancer pain were screened from the establishment of the database till now. The above literature extracted clinical efficacy, NRS score, KPS score, analgesic onset time, and duration as the main results after the screening. The 95% confidence interval (95% CI) of OR value and SMD value was used as the effect index to compare the difference in efficacy of different interventions, and the ranking was conducted. STATA 17.0 software was used for the statistical analysis of the above data. A total of 78 studies were included, including 8 interventions and 5742 participants. Based on ranking probability, the clinical effective rate of manual acupuncture combined with TSAL was the best when the intervention time was set at 4 weeks [OR = 5.42, 95% CI (1.99,14.81)], and the improvement effect on KPS score was also the best [SMD = 0.97, 95% CI (0.61, 1.33)]. Acupoint external application was the best intervention in reducing NRS score [SMD = -1.14, 95% CI (-1.90, -0.93)]. Acupoint moxibustion combined with TSAL was considered to be the most effective intervention to prolong the duration of analgesia [SMD = 1.69, 95% CI (0.84, 2.54)] and shortening the onset time of analgesia [SMD = -3.00, 95% CI (-4.54, -1.47)]. TSAL combined with manual acupuncture is the best in terms of clinical efficacy and improvement of patients' functional activity status. With the extension of treatment time, the intervention of this kind of treatment on the clinical effect is more pronounced. Acupoint external application also has a unique advantage in reducing the pain level of patients. From the point of view of analgesic duration and duration of analgesia, combined acupoint moxibustion has the best effect.