Treatment Outcomes In Patients Research Articles

Abstract 1115: Enhancing lung cancer sensitivity to chemotherapy, radiation, and chemo-radiation through inhibition of a mitotic checkpoint kinase BUB1

Abstract Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) represent two major subtypes of lung cancer, marked by challenging treatment resistance. Our study explores the inhibition of BUB1, a critical mitotic checkpoint kinase, in conjunction with radiotherapy and chemotherapy. This approach has the potential to overcome resistance, thus enhancing the efficacy of treatment and improving treatment outcomes for lung cancer patients. We analyzed BUB1 expression in lung cancer using TCGA datasets and patient tissue microarrays (TMAs). In vitro experiments used four NSCLC and two SCLC cell lines with BUB1 inhibitor (BAY1816032), Paclitaxel, Cisplatin and Olaparib. Cells were irradiated (2, 4, or 6 Gy), and assays measured proliferation, long-term effects, DNA damage, and repair. Bioinformatic analysis in NSCLC subtype, lung adenocarcinoma (LUAD) demonstrated marked overexpression of BUB1, correlated with cancer stage, tumor grade and survival. Lung cancer TMAs revealed elevated expression of BUB1 protein in SCLC that correlated with poorer survival. BUB1 inhibition (BUB1i) induced cytotoxicity in LUAD cell lines at micromolar concentrations, while nanomolar concentrations enhanced cell death significantly when combined with radiation. Furthermore, BUB1i sensitized LUAD cells to different classes of chemotherapy (Paclitaxel, Cisplatin), and PARP inhibitor (Olaparib) alone (chemo-sensitization) or with radiation therapy (chemo-radiosensitization). H2030 and H1975 demonstrated higher chemo-radiosensitization efficacy compared to A549, likely due to genetic differences, potentially including a p53 mutation that improves sensitivity by affecting DNA repair and cell cycle regulation. Preliminary investigations revealed DNA double-strand breaks, indicated by prolonged γH2AX foci, and the inhibition of the NHEJ DNA damage repair pathway after BUB1 ablation. Among SCLC cell lines, NCI-H1876 demonstrated higher radiosensitivity upon BUB1 ablation compared to NCI-H2198, potentially due to genetic differences/mutations affecting radiation response. The study highlights the potential of BUB1i in enhancing the sensitivity of NSCLC and SCLC cells to radiotherapy and chemotherapy and provide rationale to explore BUB1i as a novel approach to enhance lung cancer therapy in clinical trials. Citation Format: Shivani Thoidingjam, Sushmitha Sriramulu, Stephen L. Brown, Farzan Siddiqui, Benjamin Movsas, Shirish Gadgeel, Shyam Nyati. Enhancing lung cancer sensitivity to chemotherapy, radiation, and chemo-radiation through inhibition of a mitotic checkpoint kinase BUB1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1115.

Abstract 4652: Combined inhibition of MCL-1 and MEK reduces tumor growth in a triple-negative/inflammatory breast cancer, MEK-resistant xenograft mouse model

Abstract Background: Triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) are highly aggressive subtypes of invasive breast cancer. Our previous work showed that the MEK inhibitor (MEKi) selumetinib (AZD6244) prevents lung metastasis in a xenograft model. However, clinical studies have shown that MEKi’s as single agents have only modest activity against solid tumors. Using a genome-wide synthetic lethal siRNA screening, we identified myeloid cell leukemia-1 (MCL1) as a potential contributor to selumetinib resistance. MCL-1 is an anti-apoptotic protein associated with cell immortalization, transformation, and chemoresistance in numerous cancers. We hypothesized that MCL-1 promotes MEKi resistance in TNBC/IBC and inhibition of MCL-1 in the presence of AZD6244 overcomes this MEKi resistance. Methods & Results: To understand MCL1’s role in MEKi resistance, we established two AZD6244 -resistant TNBC/IBC cell lines: MDA-MB-231-R and SUM149-R. These cells showed increased cell viability, colony formation, migration, cells in G1 phase, CD44+CD24low, mammosphere count, anchorage-independent growth and high MCL-1 expression. MCL-1’s biological role was evaluated by transient and stably knock down (KD) of MCL-1 in the resistant cells which showed decreased cell viability, colony formation, and increased apoptosis. To understand the mechanism mediating apoptosis, we examined the expression of MCL-1’s binding partners in the MCL-1-KD-R cells in the presence of AZD6244. These cells showed a high expression of the PUMA, NOXA, BAK, and BAX in the presence of AZD6244. Further, we treated resistant cells with MEKi AZD6244 and an MCL-1i (AZD5991) that confirmed restoration of MEK sensitivity in both resistant cell lines, resulting in decreased cell viability, colony formation and increased apoptosis. We compared tumor formation capability between SUM149 parental and SUM149 resistant cells by injecting them in nu/nu mice and observed a time-dependent increase (avg. 4-fold) in tumor growth with SUM149-R cells compared to parental cells (P≤0.0001). Moreover, IHC analysis showed high expression of MCL-1 (P≤0.01), Ki67 (ns), CD44 (P≤0.0001), and ALDHA1 (P≤0.0001) in the mammary gland tumor tissues of SUM149-R-injected mice compared to SUM149-P-injected mice. Next, we evaluated the therapeutic effect of AZD6244 in mice harboring SUM149-R - MCL-1-deficient tumors. AZD6244 treatment significantly reduced tumor development in mice harboring SUM149-R - MCL-1-KD tumors compared to control mice (P<0.0001), suggesting that MCL-1 mediates MEK resistance in triple-negative/inflammatory breast cancer. Conclusion: Our results suggest that MCL-1 is important for inducing acquired MEK resistance and combining an MCL-1i with a MEKi could improve treatment outcomes of patients with TNBC or IBC who have developed resistance to single-agent MEKi. Citation Format: Mohd Mughees, Alex Tan, Lakesla Iles, Michael White, Debu Tripathy, Savitri Krishnamurthy, Jian Wang, Wendy A. Woodward, Geoffrey Bartholomeusz, Chandra Bartholomeusz. Combined inhibition of MCL-1 and MEK reduces tumor growth in a triple-negative/inflammatory breast cancer, MEK-resistant xenograft mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4652.

Abstract 5082: Novel TSHR CAR T therapy for targeting oncocytic carcinoma

Abstract Oncocytic carcinoma (Hurthle cell carcinoma) has the highest incidence of metastasis among the differentiated thyroid cancers. Metastatic disease is reported at the initial diagnosis in 10-20% of patients and 34% overall. Thyroid-stimulating hormone receptor (TSHR) expression is limited to the thyroid gland. It is abundantly expressed on thyroid tumor cells, making TSHR a compelling target for advanced thyroid cancer diagnostics and therapeutics. We developed a potent anticancer strategy for treating oncocytic carcinoma using a novel thyroid hormone stimulating receptor (TSHR)- targeted (chimeric antigen receptor) CAR T cell therapy. TSHR CAR T was generated by transducing T cells derived from healthy donors. In vitro effector functions (cytotoxicity, proliferation, degranulation) were tested in TSHR+ tumor models, and subsequent in vivo studies using NSG mice were performed to assess anti-tumor activity efficacy. We observed strong anti-tumor activity against metastatic oncocytic carcinoma cell line XCT.UC1 using the TSHR CAR T therapy in vivo. Re-challenging treated mice with XCT.UC1 cells reactivated TSHR CART cells with enhanced proliferation and complete suppression of tumor growth of the newly injected tumor cells. Our work represents a promising strategy to improve treatment outcomes of patients with metastatic oncocytic carcinoma that may provide a durable response. Citation Format: Justyna J. Gleba, Aylin Alasonyalilar-Demirer, Matthew Pawlush, Claudia Manriquez-Roman, Elizabeth L. Siegler, Robert C. Smallridge, Abba Zubair, Han W. Tun, Saad S. Kenderian, John A. Copland. Novel TSHR CAR T therapy for targeting oncocytic carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5082.

The Convention of Regular Treatment with Sphetic Conversion During Intensive Tuberculosis Treatment

Purpose: The primary objective of this research is to investigate the relationship between medication regularity and sputum conversion following the intensive treatment phase of pulmonary tuberculosis (TB) at Banyu Urip Public Health Center in Surabaya. Recognizing the importance of sputum conversion as a key determinant of treatment success in pulmonary TB, this study aims to assess the impact of medication regularity on the achievement of sputum conversion among TB patients. Methods: This study adopts an analytic correlation approach with a cross-sectional design. The study population comprises tuberculosis patients receiving treatment at the Public Health Center. Data collection involves simple random sampling of 51 respondents, focusing on variables related to medication regularity and sputum conversion. Questionnaires based on the Morisky Medication Adherence Scale-8 (MMAS-8) and observation sheets are utilized as instruments. Data analysis is conducted using logistic binary regression to examine the relationship between medication regularity and sputum conversion. Results and Discussion: Among the 51 respondents, 70.6% demonstrated regularity in treatment, with 76.5% achieving sputum conversion. The Spearman rank test analysis indicates a significant relationship between medication regularity and sputum conversion (p = 0.011; p < α = 0.05; r = 0.352). These findings suggest that adherence to medication is positively associated with successful sputum conversion following the intensive treatment phase of tuberculosis. Such results underscore the critical role of medication regularity in achieving positive treatment outcomes in TB patients. Implications of the Research: The research outcomes hold important implications for healthcare providers and policymakers involved in tuberculosis management and control. The findings highlight the significance of promoting medication regularity among TB patients to enhance treatment efficacy and increase the likelihood of sputum conversion. It underscores the importance of providing comprehensive counseling and support services to TB patients and their families, along with engaging other relevant stakeholders, to ensure adherence to treatment protocols throughout the course of therapy. Originality/Value: This study contributes to the existing literature by focusing on the relationship between medication regularity and sputum conversion specifically within the context of tuberculosis treatment. By employing logistic binary regression analysis and incorporating the MMAS-8 questionnaire, the research offers valuable insights into the factors influencing treatment outcomes in TB patients. The findings provide a basis for targeted interventions aimed at improving medication adherence and enhancing treatment success rates in pulmonary tuberculosis, thereby contributing to more effective tuberculosis management strategies.

Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review.

To review the pharmacokinetic (PK)-pharmacodynamic (PD) profiles, disease setting, dosing, and safety of oral and parenteral hypomethylating agents (HMAs) for the treatment of myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML), and to provide a multidisciplinary perspective on treatment selection and educational needs relating to HMA use. Clinical and real-world data for parenteral decitabine and azacitidine and two oral HMAs: decitabine-cedazuridine (DEC-C) for MDS and azacitidine (CC-486) for AML maintenance therapy. Differences in the PK-PD profiles of oral and parenteral HMA formulations have implications for their potential toxicities and planned use. Oral DEC-C (decitabine 35 mg and cedazuridine 100 mg) has demonstrated equivalent systemic area under the concentration-time curve (AUC) exposure to a 5-day regimen of intravenous (IV) decitabine 20 mg/m2 and showed no significant difference in PD. The AUC equivalence of oral DEC-C and IV decitabine means that these regimens can be treated interchangeably (but must not be substituted within a cycle). Oral azacitidine has a distinct PK-PD profile versus IV or subcutaneous azacitidine, and the formulations are not bioequivalent or interchangeable owing to differences in plasma time-course kinetics and exposures. Clinical trials are ongoing to evaluate oral HMA combinations and novel oral HMAs, such as NTX-301 and ASTX030. Treatment with oral HMAs has the potential to improve quality of life, treatment adherence, and disease outcomes versus parenteral HMAs. Better education of multidisciplinary teams on the factors affecting HMA treatment selection may help to improve treatment outcomes in patients with MDS or AML.

Internal mammary node abnormality in imaging studies and treatment outcomes in patients with breast cancer.

The clinical significance of mild internal mammary node (IMN) enlargement (Mild-IMN) is uncertain. This study aimed to evaluate the relationship between treatment outcomes and IMN status in patients with breast cancer who underwent postmastectomy radiation therapy between January 2010 and December 2018. Overall, 250 patients were categorized based on IMN status: Clinically normal IMN (Normal-IMN; n=172), Mild-IMN (n=39) and clinically metastatic IMN (cMet-IMN; n=39). None of the patients in the Normal- or Mild-IMN groups received IMN irradiation. In the cMet-IMN group, 25 patients underwent IMN irradiation with an IMN boost (10 Gy in 5 fractions), while 14 patients did not. The median follow-up time was 80.0 months (range, 7.2-147.6 months). The 7-year overall survival (OS), disease-free survival (DFS) and IMN recurrence-free survival (IRF) rates were 80.2, 73.0 and 93.4%, respectively. Multivariate analyses indicated that only cMet-IMN had a significant impact on OS [hazard ratio (HR), 1.66; 95% CI, 1.01-3.68; P=0.05] and DFS (HR, 1.91; 95% CI, 1.08-3.39; P=0.03), while cMet-IMN did not have a significant impact on IRF (HR, 1.66; 95% CI, 0.41-6.78; P=0.48). Additionally, receiving an IMN boost had no influence on OS (HR, 1.11; 95% CI, 0.37-2.34; P=0.84), DFS (HR, 1.28; 95% CI, 0.51-3.22; P=0.60) or IRF (HR, 1.94; 95% CI, 0.22-17.47; P=0.55). In conclusion, the impact of Mild-IMN on clinical outcomes was small. Although irradiation for cMet-IMN is important, the impact of the cMet-IMN boost with 10 Gy in 5 fractions on clinical outcomes may also be limited.

Factors determining the short-term clinical outcomes of conservative treatment in patients with supraspinatus tear

IntroductionTo identify factors influencing the better and worse changes in the Western Ontario Rotator Cuff Index of patients undergoing conservative treatment for supraspinatus tendon tear. MethodsThe study included 30 patients with supraspinatus tendon tear who underwent conservative treatment. The average duration of intervention was 35.4 days. The Western Ontario Rotator Cuff Index, shoulder range of motion, isometric muscle strength, supraspinatus tendon thickness, thickness of the supraspinatus, infraspinatus, and teres minor muscles, and acromiohumeral interval were assessed before and after the intervention. In the statistical analyses, change in the Western Ontario Rotator Cuff Index was the dependent variable, and the amount of change in each measurement variable before and after the intervention was the independent variable. ResultsThe average Western Ontario Rotator Cuff Index improved from 1067 at pre-treatment to 997 at post-treatment, but without a significant difference (p = 0.29). A multiple regression analysis revealed that supraspinatus tendon thickness and muscle strength in shoulder external rotation at 90° scaption had a significant effect on the change in the Western Ontario Rotator Cuff Index (R2 = 0.44, p < 0.01). ConclusionSupraspinatus tendon thickness and muscle strength in shoulder external rotation at 90° scaption were important factors for the Western Ontario Rotator Cuff Index score in the early stages of conservative treatment for patients with supraspinatus tendon tear.

Clot time ratio (CTR) and treatment outcomes in Apixaban-treated atrial fibrillation patients

There are clinical situations where information about the anticoagulant effects of Apixaban could be useful. Specialised methods for measuring Apixaban concentrations are not available at all medical laboratories while methods for measuring the functional effects of Apixaban, using clot time ratio (CTR), can be performed in most medical laboratories around the clock using well-established measurement procedures. The aim of this study was to investigate CTR in trough and peak samples during Apixaban treatment of atrial fibrillation and to correlate the findings to bleeds and thrombotic events. Three trough- and three peak samples from 61 patients (31 on Apixaban 5 mg twice daily and 30 on Apixaban 2.5 mg twice daily) were analysed with MRX PT DOAC. Patients were followed for 30 + /-15 months, and bleeds and thrombotic events were documented. The effect of Apixaban could be measured with MRX PT DOAC and there was a statistically significant difference between CTR in trough samples compared to peak samples (p < 0.001). A total of 21 patients suffered bleeds during follow-up; two patients suffered major bleeds, and 19 suffered minor bleeds. Patients with major bleeds had both mean peak- and mean trough CTR above the respective first to third quartile (Q1–Q3) range. Four patients suffered thromboembolic events. Generally, the peak CTRs were below or in the lower end of the peak Q1–Q3 for these patients. The new test MRX PT DOAC can be used to measure the effect of Apixaban during the treatment of atrial fibrillation. High mean peak- and mean trough CTR were seen in 2 patients with major bleeds, and low peak CTR was seen in 4 patients with thromboembolic events.

The role of molecular diagnostics in the choice of therapy for biliary tract cancers

The aim of the study was to assess the frequency and clinical significance of various molecular genetic aberrations in biliary tract tumors and to determine the optimal methods of their testing. Material and Methods. We searched the literature sources containing information on predictive molecular markers relevant for the choice of therapy in biliary tract tumors in PubMed and eLibrary databases for the period from 2010 to 2023. data from 60 studies were included in this review. Results. Biliary tract tumors are characterized by poor prognosis and low sensitivity to major systemic therapies. Nevertheless, the emergence of new targeting drugs and prescription of therapy based on the results of molecular genetic analysis can increase the life expectancy and improve the quality of life of a significant proportion of patients. The most frequently detected clinically significant abnormalities in all biliary tract tumors include HER2 gene amplification/hyperexpression (5–20 % of cases), microsatellite instability (1–2 % of cases), BRAF V600E oncogene mutation (1–2 % of cases) and KRAS G12C oncogene mutation (about 1 % of cases). Specific targetable abnormalities unique to intrahepatic cholangiocarcinomas include aberrations in the gene encoding fibroblast growth factor receptor 2, FGFR2 (10–20 % of cases) and mutations in the gene encoding the enzyme isocitrate dehydrogenase 1, IDH1 (5–30 % of cases). Very rare clinically significant molecular markers for biliary tract tumors include translocations involving the receptor tyrosine kinase genes NTRK1-3, RET, ALK and ROS1. Mutations in the genes of the dNA double-strand break repair system by the mechanism of homologous recombination are also potentially significant for the choice of therapy. First of all, these are BRCA1/2 genes, hereditary mutations in which, according to two studies, are characteristic of 5–7 % of patients with biliary cancer. Although a significant part of the above-mentioned disorders can be detected by traditional molecular biological approaches such as PCR, IHC, FISH and Sanger sequencing, a comprehensive analysis of all molecular markers of predictive value in biliary tract tumors is difficult to perform without the help of next-generation sequencing (NGS). Conclusion. To improve treatment outcomes of patients with advanced and metastatic biliary tract cancer by individualizing drug therapy, it is necessary to perform comprehensive molecular genetic analysis of tumour tissue.

Explainable machine learning for early predicting treatment failure risk among patients with TB-diabetes comorbidity

The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

Combination of urinary biomarkers and machine-learning models provided a higher predictive accuracy to predict long-term treatment outcomes of patients with interstitial cystitis/bladder pain syndrome.

To identify predictive factors for satisfactory treatment outcome of the patients with IC/BPS using urine biomarkers and machine-learning models. The IC/BPS patients were prospectively enrolled and provide urine samples. The targeted analytes included inflammatory cytokines, neurotrophins, and oxidative stress biomarkers. The patients with overall subjective symptom improvement of ≥ 50% were considered to have satisfactory results. Binary logistic regression, receiver-operating characteristic (ROC) curve, machine-learning decision tree, and random forest models were used to analyze urinary biomarkers to predict satisfactory results. Altogether, 57.4% of the 291 IC/BPS patients obtained satisfactory results. The patients with satisfactory results had lower levels of baseline urinary inflammatory cytokines and oxidative biomarkers than patients without satisfying results, including interleukin-6, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 10 (CXCL10), oxidative stress biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHDG), 8-isoprostane, and total antioxidant capacity (TAC). Logistic regression and multivariable analysis revealed that lower levels of urinary CXCL10, MCP-1, 8-OHDG, and 8-isoprostane were independent factors. The ROC curve revealed that MCP-1 level had best area under curve (AUC: 0.797). In machine-learning decision tree model, combination of urinary C-C motif chemokine 5, 8-isoprostane, TAC, MCP-1, and 8-OHDG could predict satisfactory results (accuracy: 0.81). The random forest model revealed that urinary 8-isoprostance, MCP-1, and 8-OHDG levels had the most important influence on accuracy. Machine learning decision tree model provided a higher accuracy for predicting treatment outcome of patients with IC/BPS than logistic regression, and levels of 8-isoprostance, MCP-1, and 8-OHDG had the most important influence on accuracy.

Impact of Coracohumeral Ligament Release on Treatment Outcomes in Patients with Idiopathic Adhesive Capsulitis

Background. The coracohumeral ligament restricts external rotation of the shoulder joint and, along with the upper, middle, and lower glenohumeral ligaments, participates in stabilizing the shoulder joint. There is ongoing debate regarding the division of this anatomical structure in patients with limited external rotation. Objective: to compare the treatment outcomes of patients with idiopathic adhesive capsulitis who underwent coracohumeral ligament release along with selective capsulotomy to those who underwent only partial coracohumeral ligament release. Material and Methods. We treated 85 patients with idiopathic adhesive capsulitis, who were divided into two groups: group 1 underwent selective anterior capsulotomy of the shoulder joint with the division of the middle and lower glenohumeral ligaments, biceps long head tenotomy, subacromial decompression, and partial coracohumeral ligament release; group 2 underwent a similar surgical procedure with complete coracohumeral ligament excision. The average age of the patients was 47.9±19.1 years. The function of the shoulder joint was assessed using the Constant Shoulder Score and VAS scales before surgery and at 3 and 6 months postoperatively. Results. At 3 months postoperatively, group 2 showed a slightly better functional outcome according to the Constant Shoulder Score (12.2±6.9 points) compared to group 1 (18.1±6.4 points, p=0.038). At 6 months postoperatively, group 1 had a mean Constant Shoulder Score of 15.1±7 points, while group 2 had a score of 10.1±6.3 points (p=0.02). Conclusions. Excision of the coracohumeral ligament in patients with idiopathic adhesive capsulitis allows for better functional outcomes according to the Constant Shoulder Score and VAS at both 3 and 6 months postoperatively.

Identification of the essential and critical factors of decision-making for COVID-19 patient management: a mixed-method study

Background: Understanding the contributing factors for decision-making based on the disease stage is highly crucial to improving patient care. Aim: This study aimed to identify the critical and essential factors to enhance clinical decision-making for COVID-19 patients. Methods: This mixed-method research was conducted in two phases. In the first phase, a systematic literature review was performed using defined search strategies across four databases, including PubMed, Scopus, Web of Science, and IEEE. A total of 136 studies were obtained. Next, a questionnaire-based survey was conducted to validate the findings from the review and to categorize the factors into essential and critical factors. The content validity ratio was used to categorize the factors accordingly. The identified factors were classified into six main categories based on the stages of care and the corresponding decision-making. Results: The expert panel consisted of 10 clinicians from various fields. The potential factors were categorized into six categories. A total of 293 factors were found in the literature review. The findings of the consensus survey revealed 10 factors related to the decisions on the length of stay, eight factors for ward referral decisions, one factor for decisions on home referrals, six factors for deterioration diagnosis decisions, two factors for discharge decisions, and 10 factors for decisions on intensive care unit referrals. In addition, the study identified respiratory rate, oxygen saturation at administration, arterial oxygen pressure, sequential organ failure assessment score, and glomerular filtration rate as significant decision-making factors for COVID-19 patient management. Conclusion: For medical emergencies (e.g., COVID-19 management), fewer but more significant factors may increase the efficiency of decision-making, thereby improving the quality of patient management. On this basis, this study identified the essential and critical factors for decision-making at different stages of COVID-19 patient management. Relevance for Patients: This study identified the most important factors in diagnosing the deterioration of COVID-19 patients to improve the treatment outcome of COVID-19 patients.

Impact of Procedural Variation in Endoscopic Dilation for Idiopathic Subglottic Stenosis.

A small number of Idiopathic subglottic stenosis (iSGS) patients are treated at institutions across the country. Divergence in operative techniques for endoscopic dilation (ED) of iSGS has been anecdotally recognized but not formally characterized. Additionally, the relationship between procedural variation and clinical outcome has not been studied. Secondary analysis of the NoAAC iSGS1000 cohort investigated variation in procedural techniques and treatment outcomes in patients treated with ED across high-enrolling treatment centers (enrolled >10 patients in PR-02 trial). Thirteen NoAAC centers each enrolled >10 patients treated with ED for a total of 281 subjects. There was significant variation in procedural details and rate of recurrence among institutions. Hierarchal cluster analysis revealed significant heterogeneity among institutions and clusters in all procedural variables. However, analysis demonstrated a transient delay in disease recurrence in cluster 2 which disappeared with longer longitudinal follow-up. Patient-reported outcome and peak expiratory flow data supported the potential benefit of the technical variation in Cluster 2. Distinct to cluster 2, however, was routine use of adjuvant triple medical therapy (proton pump inhibitor (PPI), antibacterial agent, and steroid inhaler). Both outcome and procedural technique vary among centers employing ED to treat iSGS. A transient delay in recurrence was observed among centers that routinely prescribed adjuvant medical therapy (antibiotic, inhaled corticosteroid, and PPI) to iSGS patients after endoscopic dilation, which was further supported by patient-reported data and peak expiratory flow data. Prospective studies are needed to understand the effects of adjuvant medical therapy on recurrence after endoscopic dilation. 4 Laryngoscope, 134:3260-3266, 2024.

Updates in BRAF V600E-Mutated Metastatic Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer worldwide, and the second leading cause of cancer death. Approximately one in five patients with CRC present with metastatic disease at diagnosis. The BRAF V600E mutation occurs in 8–12% of patients with metastatic colorectal cancer (mCRC), and is characterised by an aggressive clinical course and poor prognosis. This article is based on a webinar discussion in March 2024, between two experts in gastrointestinal cancers, Chiara Cremolini, University of Pisa, Italy; and Julien Taieb, Georges Pompidou European Hospital, Université Paris-Cité, France, both of whom have a wealth of experience and expertise in the clinical management of CRC. The experts described the most important recent advances in the treatment of BRAF V600E-mutated mCRC, including data presented at the European Society for Medical Oncology (ESMO) Congress in October 2023, and the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in January 2024. Cremolini and Taieb gave valuable insights into topics such as the aggressive nature of BRAF V600E-mutated mCRC, and how this impacts choice of treatment, patient outcomes, and quality of life, as well as the importance of early testing and monitoring. The experts also discussed how the BRAF V600E mutation impacts treatment response and outcomes in patients with microsatellite unstable (microsatellite instability [MSI]) versus microsatellite stable (MSS) tumours, and recent key clinical trials in BRAF V600E-mutated mCRC. The importance of surgery in the multidisciplinary management of patients with BRAF V600E-mutated mCRC, BRAF as a prognostic marker in resected CRC, and real-world studies in this field were also explored. Finally, Cremolini and Taieb described what the future of the management of patients with BRAF V600E-mutated mCRC might look like, and which advancements in research they would like to see.

Characteristics and Outcomes of Patients With Relapsed/Refractory Multiple Myeloma After Exposure to Lenalidomide in First Line of Therapy: A Single Center Database Review in Greece

BackgroundThe increasing use of lenalidomide (Len) in first-line (1L) therapy of multiple myeloma (MM) has led to a significant proportion of patients becoming Len-refractory following 1L treatment. However, there are limited real-world data on treatment strategies and outcomes of patients who become Len-refractory following 1L therapy. Patients and MethodsThis real-world retrospective cohort study analyzed Len-refractory and non-Len-refractory patients who received 1L Len and initiated second-line (2L) therapy at a Greek MM center. The Len-exposed cohort (n = 249) included 55.4% Len-refractory patients after 1L. ResultsCompared to non-Len-refractory patients, Len-refractory patients more frequently had high-risk cytogenetics and Revised-International Staging System-3 disease stage at diagnosis, and had shorter progression-free survival (PFS) following 1L therapy. Len-refractory versus non-Len-refractory patients more frequently received triplets (59% vs. 40%), anti-CD38 agents (20% vs. 9%) and pomalidomide (22% vs. 13%). The overall response rate was 53% for Len-refractory patients and 64% for non-Len-refractory patients in 2L therapy; median PFS was 10.7 vs. 18.3 months, respectively. Median overall survival (OS) was shorter for Len-refractory patients vs non-Len-refractory patients (23.8 vs. 53.6 months). Len refractoriness was an independent prognostic factor for both PFS and OS in Len-exposed patients. ConclusionIn this real-world Len-exposed cohort, Len-refractory patients receiving 1L Len experienced poorer survival outcomes than non-Len-refractory patients, highlighting the unmet need in this patient population which has driven the development of novel therapies.

Clinicopathologic characteristics and treatment outcomes of pancreatic cancer patients at a tertiary referral hospital in Kenya.

The global incidence of pancreatic cancer (PC) continues to steadily increase whereas its prognosis remains poor. Previous studies have suggested worse outcomes among individuals of African descent. The characteristics of patients with PC in Kenya, and their contemporary management and survival outcomes remain largely unknown. This study aimed to describe the clinical and pathologic characteristics, management, and outcomes of patients diagnosed with PC at Kenyatta National Hospital (KNH), a tertiary referral hospital in Kenya. Records of 242 patients diagnosed with PC at KNH between 1st January 2014 and 30th September 2021 were assessed in this retrospective cohort study. Data on their clinical, histopathologic, and treatment characteristics was presented as mean (± standard deviation) and/or median (interquartile range) for continuous variables and frequency (percentage) for categorical variables. Kaplan-Meier and Cox proportional hazard ratios were used for survival analysis. PC occurred in a young population, the median age being 58.5 years (inter-quartile range 35-88). The majority of tumours (54%) were metastatic at diagnosis, while 28% and 14% were stage III and stage I/II, respectively. Surgical resections with curative intent were performed on 7% overall and 44% of stage I/II cases. The majority of patients with stage I/II disease (52.9%) received chemotherapy whereas the majority with stage III and IV disease received the best supportive care only (62.7% and 64.9%, respectively). Patients who underwent surgical resection (HR for mortality 0.20, 95% CI 0.05-0.83, p = 0.021) and chemotherapy (HR for mortality 0.15, 95% CI 0.08-0.29, p < 0.001) had significantly improved survival, reflecting a more favourable stage of the disease more amenable to aggressive therapies. The median survival time was 3 months and the 1-year survival rate was 32%.

Enhancing regional control in p16-negative oropharyngeal cancer: A propensity score-matched analysis of upfront neck dissection and definitive chemoradiotherapy.

The presence of p16 and neck disease is important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC. Through this retrospective study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis. Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs 61.0%, p = 0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (hazard ratio [HR] = 0.110; 95% CI, 0.014-0.879; p = 0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia. The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.

To determine the effectiveness of Tofacitinib on treatment outcome in patients hospitalised with COVID-19 pneumonia- A longitudinal observational study in a tertiary care Hospital Mandya

The effectiveness of Tofacitinib, a Janus kinase inhibitor, in patients who are hospitalised with coronavirus disease 2019 (COVID-19) pneumonia are unclear hence this study is conducted to evaluate the efficacy of Tofacitinib on treatment outcome in patients hospitalised with COVID-19 pneumonia.All diagnosed cases of SARS COV2 who required O2 therapy at the start of the study will be undergoing routine investigations according to COVID 19 management guidelines and will be treated with adequate immunosuppression with corticosteroids. Those patients whose inflammatory markers (CRP, S LDH, D DIMER) are not decreasing after 48 hours of corticosteroids therapy may be given Tab Tofacitinib 10mg bid for a period of 14 days or till the decrease in inflammatory markers, whichever is earlier. Oxygen requirement and inflammatory markers were assessed every 3 day. Out of 27 patients who didn’t respond for corticosteroids 20 were given the drug tab tofacitinb 10mg BD. CRP in the both the steroid non responders and steroid responders groups was high till day 9, on day 14 the CRP levels were normal in 50% of steroid non responders. S LDH levels in the steroid non responders group was in the decreasing trend i.e., on day 14 it was normal in 70% of patients.. The levels of D DIMER in tofacitinib group was high till day 6, and on day 14 the D-DIMER levels were normal in 40% patients. Oxygen requirement showed drastic changes in the steroid non responders group. Among patients hospitalized with COVID-19 pneumonia, addition of Tofacitinib to steroid non responders group showed early improvement in their clinical and biochemical levels. Hence, Tab tofacitinib can be recommended an adjunct to steroids for early clinical and biochemical improvement for treatment of moderate to severe cases of COVID-19.

Promising role of traditional Indian Ayurvedic medicine in treatment, management and better clinical outcomes of COVID-19 patients: a retrospective study

IntroductionThe Coronavirus disease (COVID-19) has negatively impacted the lives of people globally. To date, no specific treatment has emerged to combat the disease. Hence, there is an urge for immediate therapy against infections like COVID-19 through the inclusion of various traditional medicines including Ayurveda. MethodsThis retrospective study was performed on 300 patients who were treated using the Holistic Ayurveda protocol at the COVID Health Care (CHC) centre. Out of 300 patients, 258 who took the AYURAKSHA Kit regularly along with the other Ayurvedic medicines for treatment were selected for this study. Demographic distribution, viral clearance, and haematological parameters of COVID-19 patients were analysed. ResultsThe maximum number of COVID-19 positive cases (31.4%) were found in the age group 20–29 years whereas the age group 40–49 years (11.52 days) and ≥ 60 years (11.5 days) took the maximum time (P = 0.035) for viral clearance. The haematological investigations showed that the Ayurveda treatment maintained the admitted patients' blood profile and coagulation profile. Strikingly, liver and kidney profiles improved post-treatment as Serum Glutamic-Oxaloacetic Transaminase (P = 0.000), Serum Glutamic Pyruvic Transaminase (P = 0.000), Urea (P = 0.000), and Creatinine (P = 0.002) levels were significantly reduced. Likewise, a significant reduction in inflammation markers like C-reactive Protein (P = 0.000), Erythrocyte Sedimentation Rate (P = 0.003), and serum Ferritin (P = 0.000) was also observed. No adverse treatment effects were observed during follow-up of the patients. ConclusionThe above outcomes showed that the Holistic Ayurveda Protocol in treating COVID-19 patients is safe, acceptable and effective. Thus, suggesting the possible integration of Ayurvedic treatment in combating such deadly diseases.