Responder Group Research Articles

Proof of principle: An animal field triage protocol for livestock and horses caught in natural disasters and major incidents

Field triage systems are available to address mass casualty incidents involving humans, but lack for animals caught in disasters. This study aimed to develop, as a proof of principle, an animal field triage protocol for livestock, horses and wildlife based on an existing human triage system. A literature review was completed, resulting in choosing the human SALT triage algorithm as a starting point, followed by an expert consultation using a two-round Delphi study to evaluate and create the final version of the triage protocol. Finally, a group of first responders were familiarized with the protocol and triage injured animals in a simulated disaster environment using a purpose-built training game and provide written feedback. For livestock and horses, consensus was reached on the use of global sorting based on the criteria ‘autonomously mobile without obvious major injuries’, and on five of six appropriate physiological criteria applied for individual health state assessment. Triaged animals were placed in one of four categories developed for applicable veterinary care, being beyond saving (black), immediate/urgent (red), delayed (yellow) and minor (green). The expert panel agreed that the veterinary triage model is probably workable for livestock and horses but not for wildlife, and has added value in natural disasters and mass casualty incidents involving animals. Validation of the protocol with first responders on the usability of the triage protocol as a proof of principle warrants a careful introduction for practical use and further evaluation during disasters affecting livestock and horses in the field.

Application of dynamic contrast enhanced ultrasound analysis in predicting early response to systemic therapy of intrahepatic cholangiocarcinoma

ObjectiveTo evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) analysis in early prediction of tumor response to systemic treatment in patients with intrahepatic cholangiocarcinoma (ICC). Patients & MethodsIn this retrospective study, patients diagnosed with ICC by core needle biopsy and histopathological results were included. All patients were diagnosed as advanced stages (stage III/IV) by the 8th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) TNM staging system. Liver contrast-enhanced ultrasound (CEUS) examination, DCE-US analysis, CT/MRI, and blood tests were performed in all patients before and 2 months after systemic treatment. CEUS procedure was performed using an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, Germany) equipped with a 5C1 MHz convex array transducer. Time-intensity curves (TIC) and quantitative parameters were created with VueBox software. According to one-year results of the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) based on CT/MRI, patients were divided into the responder group (RG) and the non-responder group (NRG). Before and 2 months after systemic therapy, the DCE-US perfusion parameters was compared using the paired-sample t test and the Wilcoxon test. ResultsFrom September 2020 to December 2021, a total of 24 patients diagnosed with advanced ICC were included (11 males, 13 females, mean age 59.4 ± 1.8 years). According to the one year of m-RECIST results, 17 cases (70.8 %) were classified as non-responders by the final m-RECIST criteria, while 7 cases (19.2 %) were responders. Comparing before and 2 months after therapy, the RG took longer time to reach peak intensity, and the peak intensity of TIC was lower. While the TICs of NRG revealed faster enhancement after therapy. Among all DCE-US quantitative parameters, PE (peak enhancement), WiR (wash-in rate), WiPI (wash-in perfusion index) and WoR (wash-out rate) reduced significantly following 2 months of systemic therapy in RG (P < 0.05). Comparing to RG, PE and WiPI decreased slightly 2 months after therapy in NRG (P < 0.05). ConclusionsThe DCE-US analysis with quantitative parameters has the potential value to make early and quantitative evaluation of treatment response to systemic therapy in ICC patients.

Abstract 2803: Identification of microbiome and predictive immune biomarkers in patients with advanced non-small lung cancer treated with pembrolizumab with or without chemotherapy

Abstract Background: Recent studies have shown that gut microbiota modulates antitumor immunity, and affect clinical efficacy of immune checkpoint inhibitors, including anti-programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. We aimed to explore the metagenomic profiles of previously untreated, treatment naïve, stage IV non-small cell lung cancer (NSCLC) treated with pembrolizumab, an anti-PD1 agent with or without platinum-based chemotherapy and identify distinct ecological niche between responder and non-responder groups. Methods: We performed metagenome sequencing, whole exome sequencing (WES), and RNA sequencing (RNA-seq) on 50 patients with stage IV NSCLC, including adenocarcinoma (N=31) and squamous cell carcinoma (N=22). We employed Dirichlet Multinomial Mixtures (DMM) community typing to cluster microbial community profiling data at the genus level and analyzed the changes in microbial composition and diversity between enterotype 1 (E1, N=27) and enterotype 2 (E2, N=23). Mutation landscape including genomic alterations in relation to immune response was analyzed between responders and non-responders using WES data. Differentially expressed genes (DEGs), Gene Set Enrichment Analysis (GSEA), and immune deconvolution analysis were carried out using RNA-seq data to analyze molecular profiling of two enterotypes between the responder (N=15) and non-responder (N=35) groups. Results: The two enterotypes exhibited distinct microbial abundances and alpha diversity indices. Abundances of members of Bacteroidaceae (P=0.011) and Oscillospiraceae (P&amp;lt;0.001) were higher in E2 members, and enrichment of Lactobacillaceae (P=0.006) and Bifidobacteriaceae (P=0.041) were higher in E1. Compared to E1, the number of observed bacterial species (P&amp;lt;0.001) and Shannon index (P&amp;lt;0.001) was significantly higher in E2, indicating a healthier gut environment. The proportion of responders was higher in E2 than in E1 cluster. Comparison between responders and non-responder groups within each enterotype revealed that Lactobacillaceae showed an association with the response in E2 cluster. Mutation landscape revealed TP53 mutation as the most common mutation, more frequently observed in the E2 (100%) than in the E1 (56%) cluster. Conclusion: We explored the association between the gut microbiome and clinical response to pembrolizumab with or without combination with chemotherapy and found that E2 cluster enriched with Lactobacillaceae is associated with treatment response. Further analysis with larger cohort is ongoing. Citation Format: Jii Bum (Joy) Lee, Su-Jin Choi, Gang-Taik Lee, Junwon Yang, Hyun-Seok Oh, Arim Min, Bo-Eun Kwon, Seong-san Kang, Sujeong Baek, Dong Kwon Kim, Jae Hwan Kim, Sun Min Lim, Min Hee Hong, Kyoung-Ho Pyo, Byoung Chul Cho. Identification of microbiome and predictive immune biomarkers in patients with advanced non-small lung cancer treated with pembrolizumab with or without chemotherapy [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 2803.

Abstract 5651: Personalized transcriptomic profiling for advanced prostate cancer: Guiding second-generation hormonal drug selection

Abstract Introduction: Second-generation hormonal drugs have demonstrated significant efficacy in extending the survival of patients with advanced prostate cancer. These drugs operate through two distinct molecular mechanisms: inhibition of androgen biosynthesis and blockade of the androgen receptor. However, due to concerns of side effects, concurrent usage of multiple drugs is not recommended. A notable challenge is the eventual development of drug resistance, rendering all second-generation hormonal therapies ineffective. Currently, there is a lack of guidelines for helping patients choose the most suitable drug. In the context of pharmacogenomics, genetic differences can influence drug susceptibility and efficacy, with variations in genomic sequences and regulatory mechanisms impacting drug response at the transcriptional and translational levels. Considered the rapid processing capabilities of Affymetrix transcriptomic microarrays, we hypothesized that distinct gene signatures in patients who respond well or poorly to second-generation hormonal drugs could be identified and could act as a companion diagnostic tool. Methods: We enrolled 180 advanced prostate cancer patients, who fulfilled Taiwan national health insurance criteria of using second-generation hormonal drugs, from seven medical centers or regional hospitals in Taiwan at 3 time points: prior to drug administration, 3 months after treatment started and drug resistance developed. The RNA expression data and clinical parameters were analyzed, and classification models were built using IPA and R. Good or poor responders were defined by 3-month prostate-specific antigen (PSA) lowered by 90 percent. Results:: Differential expression and enrichment analyses post-treatment highlighted the activation of NF-kappa B signaling and various immune cell pathways. Notably, pathways related to primary immunodeficiency and IL-17 became prominent following the development of drug resistance. At the initial stages, distinct alterations in cell cycle pathways, particularly G1/S and G2/M, were observed between good and poor responders. This was elucidated through principal component analysis and subsequent dbscan clustering. To further distinguish between these responder groups, we utilized an integrative approach for feature selection, combining support vector machine, random forest classifier, and lasso regression. Despite the innovative approach, the model's error rate stood at approximately 15%, attributed mainly to the limited number of cases. Conclusion: Our study highlights the potential of using transcriptomic analysis to predict responses to second-generation hormonal drugs in advanced prostate cancer, paving the way for personalized treatment strategies. However, the need for larger cohort studies is evident to refine these predictive models and enhance their accuracy. Citation Format: Li-Hsin Chang, Hao-Han Chang, Xin-Yi Lin, Shu-Chi Wang, Chih-Pin Chuu, Deng-Neng Chen, Shu-Pin Huang, Chia-Yang Li. Personalized transcriptomic profiling for advanced prostate cancer: Guiding second-generation hormonal drug selection [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 5651.

Health-related quality of life and neurocognitive functioning in patients with recurrent glioblastoma treated with intracerebral immune checkpoint inhibition.

After glioblastoma (GB) recurrence, prognosis is very cumbersome. Therefore, health-related quality of life (HRQoL) and neurocognitive functioning (NCF) have become important endpoints in clinical trials when evaluating novel treatments. We aimed to evaluate the HRQoL and NCF in patients with recurrent glioblastoma (rGB) treated with a combination of surgical intervention (reoperation or biopsy) and intracerebral immune checkpoint inhibition. Patients who participated in the trial (N = 23), at a single-center university hospital were included. Data were collected using 3 patient-reported outcome measures (EORTC-QLQ-C30, EORTC-QLQ-BN20, and HADS) and computerized NCF testing. In the responder group, baseline values were compared to results at a 6-month follow-up. Additionally, exploratory analyses compared baseline HRQoL and NCF between responders and non-responders. There were five responders and 18 non-responders. When comparing the mean and individual baseline with follow-up results for the responders, we observed overall a stable to slight clinically relevant improvement of HRQoL in multiple subsets of the questionnaires while maintaining a stable NCF. One patient deteriorated on anxiety and depression symptoms from baseline to follow-up. In patients that responded to intracerebral immunotherapy in our institutional trial, HRQoL and NCF remained stable over time, suggesting that no detrimental effect on cognitive function or quality of life may be expected with this treatment approach. Furthermore, there seems to be an overall tendency for responders to score better on HRQoL and NCF than non-responders at baseline.

Efficacy and Predictive Factors of Oral Spironolactone Treatment in Chronic Central Serous Chorioretinopathy.

To evaluate the efficacy of spironolactone in the treatment of chronic central serous chorioretinopathy (CSC) and identify imaging characteristics that can predict the benefit of spironolactone treatment. Patients with chronic CSC were treated with spironolactone (20 mg/tid) and followed for 6 months. The primary outcome measure was complete resolution of the subretinal fluid (SRF), and the best-corrected visual acuity (BCVA), the SRF area, the central macular thickness (CMT), the subfoveal choroidal thickness (SFCT), and the density of the choriocapillaris vessel and adverse events were secondary outcome measures. Patients who presented complete resolution of SRF were included in the responder group and the other patients who had moderate or no resolution were included in the nonresponder group. Imaging characteristic comparisons between the responder and nonresponder groups were performed with regression analyses to identify factors that are predictive of a good response to treatment. Forty-two eyes of 42 patients with a mean age of 46.06 ± 6.66 years were included. A total of 57.1% of the patients achieved a complete resolution of SRF. The mean SRF area, CMT, and SFCT decreased significantly (all P < 0.05) throughout the follow-up period and BCVA improved slightly (P > 0.05). The vascular density of the choriocapillaris of the fellow eyes did not vary significantly during treatment. Logistic regression analysis revealed that SFCT (P=0.002) and the intact ellipsoid zone (P=0.001) were correlated with disease resolution. A relatively higher baseline SFCT was a predictive factor associated with a good response to treatment according to multivariate analysis. This study suggested that oral spironolactone could be an effective and safe therapy for chronic CSC patients. Eyes with a higher baseline SFCT and intact ellipsoid zone could have a good response. These parameters are an important prognostic marker.

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.

Transcutaneous tibial nerve stimulation in patients with multiple sclerosis and overactive bladder: a real-life clinical and urodynamic assessment.

The aims of the present study were to assess the effectiveness of transcutaneous tibial nerve stimulation (TTNS) on overactive bladder (OAB) symptoms and on urodynamic parameters in patients with multiple sclerosis (PwMS) and to seek predictive factors of satisfaction. All PwMS who performed 12-24weeks of TTNS and who underwent urodynamic assessment before and after treatment between June 2020 and October 2022 were included retrospectively. Data collected were bladder diaries, symptoms assessed with Urinary Symptoms Profile (USP), and urodynamic parameters (bladder sensations, detrusor overactivity, and voiding phase). Patients with improvement rated as very good or good on Patient Global Impression of Improvement (PGI-I) score were considered as responders. Eighty-two patients were included (mean age: 47.1 ± 11.5years, 67 (82%) were women). The mean USP OAB sub-score decreased from 7.7 ± 3.5 to 6.0 ± 3.4 (p < 0.0001). On bladder diaries, voided volumes, void frequency, and the proportion of micturition done at urgent need to void significantly improved with TTNS (p < 0.05). No significant change was found in urodynamic parameters. According to the PGI-I, 34 (42.5%) patients were good responders. The only parameter associated with higher satisfaction was the percentage of micturition done at urgent need to void before the initiation of the treatment (39.8% ± 30.5 in the responder group vs 25.1% ± 25.6 in the low/no responder group; p = 0.04). TTNS improves OAB symptoms in PwMS, without significant changes on urodynamics. A high rate of strong or urgent need to void in daily life was associated with higher satisfaction.

What patients with advanced cancer experience as helpful in navigating their life with a long-term response: a qualitative study

PurposeDespite improved survival for people with advanced cancer due to new medical treatments, a growing group of long-term responders (LTRs) has to learn to live with uncertainties that affect several life domains. At the core of their experience, they neither feel like a patient nor feel healthy. Despite growing awareness of LTRs’ experiences, learning more about how they cope with their long-term response can provide insight into how to best support them. Our study aimed to gain a deeper understanding what LTRs experience as helpful in navigating life with a long-term response.MethodsWe conducted an exploratory qualitative study using thematic data analysis. Semi-structured in-depth interviews were conducted with 17 participants with advanced melanoma or lung cancer with confirmed response or long-term stable disease while on immuno- or targeted therapy.ResultsLTRs reported several strategies to navigate life with a long-term response, for example, by involving the social environment, seeing uncertainty as an opportunity, and being present in the moment. This helped them to reclaim a sense of control, alter their perspective, and reshape their lives according to their values.ConclusionUsing different coping strategies enables LTRs to acknowledge both their sick and healthy side. Striking a healthy balance between being oriented on feeling sick or feeling healthy can help LTRs and their close others to navigate life with a long-term response. Healthcare professionals can provide support by recognizing whether LTRs are oriented at feeling sick or healthy, and by actively involving close others during medical appointments.

Capillary refill time assessment after fluid challenge in patients on venoarterial extracorporeal membrane oxygenation: A retrospective study

BackgroundMonitoring fluid therapy is challenging in patients assisted with Veno-arterial ECMO. The aim of our study was to evaluate the usefulness of capillary refill time to assess the response to fluid challenge in patients assisted with VA-ECMO. MethodsRetrospective monocentric study in a cardiac surgery ICU. We assess fluid responsiveness after a fluid challenge in patients on VA-ECMO. We recorded capillary refill time before and after fluid challenge and the evolution of global hemodynamic parameters. ResultsA total of 27 patients were included. The main indications for VA-ECMO were post-cardiotomy cardiogenic shock (44%). Thirteen patients (42%) were responders and 14 non-responders (58%). In the responder group, the index CRT decreased significantly (1.7 [1.5; 2.1] vs. 1.2 [1; 1.3] s; p = 0.01), whereas it remained stable in the non-responder group (1.4 [1.1; 2.5] vs. 1.6 [0.9; 1.9] s; p = 0.22). Diagnosis performance of CRT variation to assess response after fluid challenge shows an AUC of 0.68 (p = 0.10) with a sensitivity of 79% [95% CI, 52–92] and a specificity of 69% [95% CI, 42–87], with a threshold at 23%. ConclusionIn patients treated with VA-ECMO index capillary refill time is a reliable tool to assesses fluid responsiveness. SpecialtyCritical care, Cardiac surgery, ECMO.

Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery.

Warfarin is widely used for the prevention and treatment of thrombotic events. This study aimed to examine the influence of gene polymorphisms on the early stage of warfarin therapy in patients following heart valve surgery. Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed. Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability. The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.

Lung Ultrasound Evaluation of Aeration Changes in Response to Prone Positioning in Acute Respiratory Distress Syndrome (ARDS) Patients Requiring Venovenous Extracorporeal Membrane Oxygenation: An Observational Study.

Prone positioning (PP) has been proven to be a beneficial approach in enhancing survival outcomes for patients with severe acute respiratory distress syndrome (ARDS) who need venovenous extracorporeal membrane oxygenation (V-V ECMO) support. The study utilized bedside lung ultrasound (LUS) to evaluate changes in lung aeration caused by PP in ARDS patients receiving V-V ECMO. This retrospective single-center study involved adult ARDS patients requiring V-V ECMO. The assessment of LUS involved examining specific dorsal lung regions, encompassing 16 areas, during three pre-defined time points: baseline (10 minutes prior), three-hour PP positioning, and 10-minute post-supine repositioning, all within the initial three days. Based on the oxygenation response to PP, patients were categorized into responder and non-responder groups. The primary outcome was LUS score changes during the initial three-day period. Secondary outcomes examined the impact of PP on the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) (P/F) ratio, V-V ECMO weaning success, length of ICU stay, and hospital survival. Among the enrolled patients (27 in total), 16 were responders and 11 were non-responders. In the responder group, the global LUS score underwent a significant reduction from 26.38 ± 4.965 at baseline to 20.75 ± 3.337 (p < 0.001) after the first PP session, which further decreased to 15.94 ± 2.816 (p< 0.001) after three days. However, no significant differences were observed among PP non-responders. The oxygenation reaction yielded comparable results. There was a significant correlation between the duration of daily PP and the reduction in global LUS score among PP responders (r = -0.855, p < 0.001). In cases where the global LUS score decreased by > 7.5 after three days of PP, the area under the receiver operating characteristic curve (AUROC) for predicting ECMO weaning success was 0.815, while it was 0.761 for predicting hospital survival. LUS has the potential to predict the response to PP and evaluate the prognosis of ARDS patients with V-V ECMO, althoughmore studies are demanded in the future.

Neutrophil to lymphocyte ratio and systemic immune-inflammatory index as markers of response to autologous hematopoietic stem cell transplantation in persons with multiple sclerosis.

Biomarkers that help to evaluate the immune system and could be useful in multiple sclerosis (MS) are the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). The objective of this work is to evaluate the significance of the SII index, PLR, and NLR before and after transplantation in individuals with MS who underwent autologous hematopoietic stem cell transplant (aHSCT) at a single institution. Patients with MS who received an aHSCT between 2017 and 2022 were included in the study. NLR, PLR, and SII index were calculated prior to the transplant and 100 days after, and evaluation of the expanded disability status scale (EDSS) was done before the transplant and 12 months after. The cohort was divided into two groups: aHSCT responders (R) and nonresponders (NR). Fifty-eight individuals were examined: 37 patients in the responders group R group and 21 in NR group. There was no statistically significant difference in the SII, NLR, and PLR prior to the transplant, however at 100 days post-HSCT, NLR in the R group was 1.8 versus 3.1 in the NR group (p = 0.003), PLR was 194 versus 295, respectively (p = 0.024), meanwhile SII index was 489.5 versus 729.3 (p < 0.001). High NLR and SII index values after the aHSCT were associated with a worsening in the EDSS score. However, since this is the first ever study that compared NLR and SII index with the aHSCT response in persons with MS, further studies must be performed to corroborate this information.

Occurrence of Existing BCR-ABL Baseline Mutations and Associated Haplotype (NmR) Among CML Patients with Diverse IM Response: A Hospital-based Study from North-East India.

Highly polymorphic BCR-ABL kinase domains have been reported to harbor more than a hundred mutations, and among these, 40-60% have been identified as influencers of imatinib mesylate (IM) resistance. The emergence of IM resistance poses a significant challenge in the management of Chronic Myeloid Leukemia (CML). M351T (rs121913457), E255K (rs387906517), and Y253H (rs121913461) are of particular clinical significance due to their association with high-level imatinib resistance. This study was conducted to investigate the potential role of three significant SNPs in CML progression due to IM resistance. During the study period from 2018 to 2022 (48months), the blood samples from 219 Reverse transcriptase-PCR-confirmed CML patients following RNA extraction and cDNA preparation were subjected to M351T, E255K, and Y253H mutation analysis by PCR-RFLP. After agarose gel visualization, the samples were subjected to Sanger sequencing to confirm the nucleotide change at the polymorphic loci. The wild-type genotype of all three ABL1 SNPs under investigation exhibits a significant reduction in frequency among IM non-responders compared to the responder group. The CGT haplotype frequency exhibits a significant difference between IM responder (4.2%) and non-responder (11.8%) (p = 0.002 < 0.05). Further, CGC haplotype was observed solely among the imatinib non-responder patients with a frequency percentage of 3.3% (p = 0.004), whereas the said genotype was absent among the responder group. A reduced overall survival rate was observed with deviation from wild-type genotype (M351T loci (T > C) with 1.217 times, E255K (G > A) with 1.485 and Y253H (T > C) with 1.399 times increase in hazard ratio) thereby enhancing mortality risk due to disease progression. The significant increase in the frequency of M351T, E255K, and Y253H loci among the IM non-responder group indicated their probable association with the development of IM resistance among CML patients. A haplotype frequency distribution pattern analysis of ABL1 loci further identified the CGC haplotype as an independent predictor for IM resistance. As such the study highlights the importance of patient characteristics, genotype distribution, and haplotype frequency distribution in predicting the response to IM treatment and clinical outcomes of CML patients.

Tumor Characteristics and Treatment Responsiveness in Pembrolizumab-Treated Non-Small Cell Lung Carcinoma.

Pembrolizumab, a widely used immune checkpoint inhibitor (ICI), has revolutionized the treatment of non-small cell lung cancer (NSCLC). Identifying unique tumor characteristics in patients likely to respond to pembrolizumab could help the clinical adjudication and development of a personalized therapeutic strategy. In this retrospective study, we reviewed the clinical data and pathological features of 84 NSCLC patients treated with pembrolizumab. We examined the correlation between the clinical and demographic characteristics and the tumor histopathologic features obtained before immunotherapy. The response to pembrolizumab therapy was evaluated via the Response Evaluation Criteria in Solid Tumors (RECIST). The clinical data and cancer tissue characteristics were assessed and compared among three groups according to the following RECIST: the responsive group (RG), the stable disease group (SD), and the progressive disease group (PD), where the RG comprised patients with either a complete response (CR) or a partial response (PR). The overall survival rate of the RG group was significantly higher than the SD and PD groups. In addition, the percentage of pre-treatment viable tumor cell content in the RG and SD groups was significantly higher. At the same time, the extracellular stroma proportion was significantly lower than that of the PD group. The number of tumor-infiltrating lymphocytes (TILs) in the RG group was significantly higher than in the PD group. There were no significant differences in tumor necrosis, the stroma composition, PD-L1 expression level (TPS 1-49% vs. ≥50%), and treatment response. In conclusion, our population of NSCLC patients who experienced positive treatment responses to pembrolizumab therapy had a better prognosis compared to patients with either SD or PD. Moreover, the relative proportions of viable tumor cells to tumor-associated lymphocytes were associated with responsiveness to treatment. It is expected that larger prospective clinical studies will further validate these findings.

Detection of seizures with ictal tachycardia, using heart rate variability and patient adaptive logistic regression machine learning methods: A hospital-based validation study.

Automated seizure detection of focal epileptic seizures is needed for objective seizure quantification to optimize the treatment of patients with epilepsy. Heart rate variability (HRV)-based seizure detection using patient-adaptive threshold with logistic regression machine learning (LRML) methods has presented promising performance in a study with a Danish patient cohort. The objective of this study was to assess the generalizability of the novel LRML seizure detection algorithm by validating it in a dataset recorded from long-term video-EEG monitoring (LTM) in a Brazilian patient cohort. Ictal and inter-ictal ECG-data epochs recorded during LTM were analyzed retrospectively. Thirty-four patients had 107 seizures (79 focal, 28 generalized tonic-clonic [GTC] including focal-to-bilateral-tonic-clonic seizures) eligible for analysis, with a total of 185.5 h recording. Because HRV-based seizure detection is only suitable in patients with marked ictal autonomic change, patients with >50 beats/min change in heart rate during seizures were selected as responders. The patient-adaptive LRML seizure detection algorithm was applied to all elected ECG data, and results were computed separately for responders and non-responders. The patient-adaptive LRML seizure detection algorithm yielded a sensitivity of 84.8% (95% CI: 75.6-93.9) with a false alarm rate of .25/24 h in the responder group (22 patients, 59 seizures). Twenty-five of the 26 GTC seizures were detected (96.2%), and 25 of the 33 focal seizures without bilateral convulsions were detected (75.8%). The study confirms in a new, independent external dataset the good performance of seizure detection from a previous study and suggests that the method is generalizable. This method seems useful for detecting both generalized and focal epileptic seizures. The algorithm can be embedded in a wearable seizure detection system to alert patients and caregivers of seizures and generate objective seizure counts helping to optimize the treatment of the patients.

Is antipsychotic augmentation associated with improved functioning in patients on clozapine?

We aimed at exploring the relationship between functional outcomes in patients on clozapine augmented with antipsychotics in treatment-resistant schizophrenia using standard outcome measures Health of Nation Outcome Scales (HoNOS) and Life Skills Profile (LSP-16). In a cross-sectional study of 83 patients on clozapine treated in a psychiatric rehabilitation hospital, the association between the primary outcome measure, LSP-16 including its subscales, and treatment with antipsychotic augmentation (AA) were analysed using linear regression. The presence of moderate-to-severe positive symptoms on the HoNOS 6 dichotomised item measure was the only statistically significant predictor of functional impairment as determined by total LSP-16 score.The group of patients with ongoing positive symptoms (partial responders) were characterised by higher total LSP-16 scores, higher numbers of AA agents, and higher chlorpromazine equivalence. There was an inverse linear relationship between chlorpromazine equivalence of AA and total score of LSP-16 scale in the group of partial responders. Augmentation with other antipsychotic agents was associated with higher functioning in a cross-sectional study of patients with schizophrenia with poor response of positive symptoms to clozapine. This might be an important clinical factor to consider when prescribing antipsychotics to patients with clozapine-resistant schizophrenia.

Evaluation of the satisfaction and experiences of oncology patients and doctors using teleconsultation during the COVID-19 pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, the Gustave Roussy Cancer Center introduced teleconsultation via telephone, as an alternative to face-to-face consultation to reduce patient hospital visits. This study was designed to assess patient and doctor satisfaction with this modality of care in oncology patient care during the period of the pandemic and beyond. We designed two questionnaires based on validated scores to assess satisfaction from teleconsultation in patients (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) and doctors (Telehealth Usability Questionnaire [TUQ]), and anxiety levels in both groups (anxiety section of the Hospital Anxiety and Depression Scale [HADS], HADS-A). These were electronically sent to patients and doctors with experience of at least one remote consultation during the first wave of the COVID-19 pandemic. 239 patients and 32 doctors were eligible for the analyses. In the patient group, the mean satisfaction scores were 79.5 (SD 18.1) and 74.92 (SD 15.3) for EORTC OUT-PATSAT 35 and TSQ, respectively. In the doctor group, the mean satisfaction scores were 67.1 (SD 12.7) and 64.9 (SD 13.9) for TUQ and TUQ for Skype for Business, respectively. 65.7% of patients and 81.2% of doctors had no/low anxiety. Univariable analyses in patients showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores with anxiety and gender, with lower mean scores in women compared to men. Multivariable analysis showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores to anxiety in both patients and doctors. Teleconsultation via telephone is an acceptable modality of care for oncology patients, with high satisfaction from its implementation during the pandemic reported by patients and doctors. This was consistent across responder groups with different characteristics. An individualized approach to patients should be implemented for the safe and effective use of teleconsultation in oncology beyond the pandemic.

Usability of home use medical technology: The patient perspective

Introduction Technological advancements have increased the scope and range of home-use medical devices. These have allowed development of care at home. This requires appropriate understanding of patient's needs with regards to such devices for safe use of medical technology at home and minimise usability errors. This study sought to investigate patient experiences of usability and to identify future requirements for such devices Methods A qualitative mixed methods study was chosen. The participants were asked to complete a survey which included both multiple-choice and free-text entry questions. Participant recruitment was through purposive and snowball sampling approaches. All participants were required to have direct experience in using a medical device. Data were thematically analysed. Results There were 360 responses by patients, parents and carers. 503 devices were used by these participants. 99.4% used their device(s) on a daily basis. The largest group of responders were from type 1 diabetic patients. Multiple usability challenges were reported with respect to training, device interoperability, development of workarounds and the device-user interfaces. Device acceptance and their costs were also raised as issues for concern. A list of usability challenges was compiled. Conclusions Patients and other end users continue to experience multiple usability challenges in the use of medical devices at home despite guidance from regulatory bodies. Better post market studies are required to generate evidence to enable the improved design and safety of the device. This should be accompanied with an evaluation of improvements in patient satisfaction and their compliance with monitoring and treatment.

Molecular effects of cardiac contractility modulation in patients with heart failure of ischemic aetiology uncovered by transcriptome analysis.

Cardiac contractility modulation (CCM) is based on electrical stimulation of the heart without alteration of action potential and mechanical activation, the data on its fundamental molecular mechanisms are limited. Here we demonstrate clinical and physiological effect of 12 months CCM in 29 patients along with transcriptomic molecular data. Based on the CCM effect the patients were divided into two groups: responders (n = 13) and non-responders (n = 16). RNA-seq data were collected for 6 patients before and after CCM including 3 responders and 3 non-responders. The overall effect of CCM on gene expression was mainly provided by samples from the responder group and included the upregulation of the genes involved in the maintenance of proteostasis and mitochondrial structure and function. Using pathway enrichment analysis, we found that baseline myocardial tissue samples from responder group were characterized by upregulation of mitochondrial matrix-related genes, Z disc-protein encoding genes and muscle contraction-related genes. In summary, twelve months of ССM led to changes in signaling pathways associated with cellular respiration, apoptosis, and autophagy. The pattern of myocardial remodeling after CCM is associated with initial expression level of myocardial contractile proteins, adaptation reserves associated with mitochondria and low expression level of inflammatory molecules.