Monitoring Of Response Research Articles

Using Progress Feedback to Enhance Treatment Outcomes: A Narrative Review.

We face increasing demand for greater access to effective routine mental health services, including telehealth. However, treatment outcomes in routine clinical practice are only about half the size of those reported in controlled trials. Progress feedback, defined as the ongoing monitoring of patients' treatment response with standardized measures, is an evidence-based practice that continues to be under-utilized in routine care. The aim of the current review is to provide a summary of the current evidence base for the use of progress feedback, its mechanisms of action and considerations for successful implementation. We reviewed ten available meta-analyses, which report small to medium overall effect sizes. The results suggest that adding feedback to a wide range of psychological and psychiatric interventions (ranging from primary care to hospitalization and crisis care) tends to enhance the effectiveness of these interventions. The strongest evidence is for patients with common mental health problems compared to those with very severe disorders. Effect sizes for not-on-track cases, a subgroup of cases that are not progressing well, are found to be somewhat stronger, especially when clinical support tools are added to the feedback. Systematic reviews and recent studies suggest potential mechanisms of action for progress feedback include focusing the clinician's attention, altering clinician expectations, providing new information, and enhancing patient-centered communication. Promising approaches to strengthen progress feedback interventions include advanced systems with signaling technology, clinical problem-solving tools, and a broader spectrum of outcome and progress measures. An overview of methodological and implementation challenges is provided, as well as suggestions for addressing these issues in future studies. We conclude that while feedback has modest effects, it is a small and affordable intervention that can potentially improve outcomes in psychological interventions. Further research into mechanisms of action and effective implementation strategies is needed.

FDA's proposed rule and its regulatory impact on emerging and reemerging neglected tropical diseases in the United States.

Diagnosing infectious diseases significantly influences patient care, aiding in outbreak identification, response, and public health monitoring. However, the range of FDA-approved molecular tests remains notably limited, especially concerning neglected tropical diseases (NTDs). Drawing upon our experience as one of the largest healthcare networks in the greater New York metropolitan area, this viewpoint manuscript aims to spotlight the existing diagnostic landscape and unmet clinical needs for 4 emerging NTDs increasingly prevalent in the United States, additionally, it delves into the possible adverse effects of the FDA's Proposed Rule on Laboratory-Developed Tests for these clinical conditions and the broader spectrum of NTDs.

Training and Comparison of nnU-Net and DeepMedic Methods for Autosegmentation of Pediatric Brain Tumors.

Tumor segmentation is essential in surgical and treatment planning and response assessment and monitoring in pediatric brain tumors, the leading cause of cancer-related death among children. However, manual segmentation is time-consuming and has high interoperator variability, underscoring the need for more efficient methods. After training, we compared 2 deep-learning-based 3D segmentation models, DeepMedic and nnU-Net, with pediatric-specific multi-institutional brain tumor data based on multiparametric MR images. Multiparametric preoperative MR imaging scans of 339 pediatric patients (n = 293 internal and n = 46 external cohorts) with a variety of tumor subtypes were preprocessed and manually segmented into 4 tumor subregions, ie, enhancing tumor, nonenhancing tumor, cystic components, and peritumoral edema. After training, performances of the 2 models on internal and external test sets were evaluated with reference to ground truth manual segmentations. Additionally, concordance was assessed by comparing the volume of the subregions as a percentage of the whole tumor between model predictions and ground truth segmentations using the Pearson or Spearman correlation coefficients and the Bland-Altman method. The mean Dice score for nnU-Net internal test set was 0.9 (SD, 0.07) (median, 0.94) for whole tumor; 0.77 (SD, 0.29) for enhancing tumor; 0.66 (SD, 0.32) for nonenhancing tumor; 0.71 (SD, 0.33) for cystic components, and 0.71 (SD, 0.40) for peritumoral edema, respectively. For DeepMedic, the mean Dice scores were 0.82 (SD, 0.16) for whole tumor; 0.66 (SD, 0.32) for enhancing tumor; 0.48 (SD, 0.27) for nonenhancing tumor; 0.48 (SD, 0.36) for cystic components, and 0.19 (SD, 0.33) for peritumoral edema, respectively. Dice scores were significantly higher for nnU-Net (P ≤ .01). Correlation coefficients for tumor subregion percentage volumes were higher (0.98 versus 0.91 for enhancing tumor, 0.97 versus 0.75 for nonenhancing tumor, 0.98 versus 0.80 for cystic components, 0.95 versus 0.33 for peritumoral edema in the internal test set). Bland-Altman plots were better for nnU-Net compared with DeepMedic. External validation of the trained nnU-Net model on the multi-institutional Brain Tumor Segmentation Challenge in Pediatrics (BraTS-PEDs) 2023 data set revealed high generalization capability in the segmentation of whole tumor, tumor core (a combination of enhancing tumor, nonenhancing tumor, and cystic components), and enhancing tumor with mean Dice scores of 0.87 (SD, 0.13) (median, 0.91), 0.83 (SD, 0.18) (median, 0.89), and 0.48 (SD, 0.38) (median, 0.58), respectively. The pediatric-specific data-trained nnU-Net model is superior to DeepMedic for whole tumor and subregion segmentation of pediatric brain tumors.

Quantum Biosensors: Principles and Applications in Medical Diagnostics

Abstract Originating at the intersection of physics and biosensing, quantum biosensors (QB) are transforming medical diagnostics and personalized medicine by exploiting quantum phenomena to amplify sensitivity, specificity, and detection speed compared to traditional biosensors. Their foundation lies in the fusion of biological entities like DNA, proteins, or enzymes with quantum sensors, which elicits discernible alterations in light emissions when interacting with sample molecules. Their prowess in identifying disease-linked biomarkers presents an avenue for early diagnoses of conditions like Alzheimer's and cancer. Beyond this, they enable real-time monitoring of treatment responses by capturing the dynamism of biomarkers, but QB still face challenges, such as issues of stability, reproducibility, and intricate quantum interactions. Moreover, seamless integration into prevailing diagnostic frameworks necessitates careful consideration. Looking ahead, the evolution of QB navigates uncharted territories. Innovations in fabrication techniques, interdisciplinary collaborations, and standardization protocols emerge as pivotal areas of exploration. This comprehensive discourse encapsulates QB's principles, diverse iterations, and burgeoning medical utilities. It delves into inherent challenges and limitations, shedding light on the potential trajectories of future research. As QB continues to evolve, its potential to redefine medical diagnostics becomes increasingly tangible. The saga of QB resonates with possibilities, poised to reshape the diagnostic landscape profoundly.

ANOMALY DETECTION SYSTEM

In an era marked by dynamic security challenges, real-time CCTV anomaly detection systems have emerged as a cornerstone in contemporary security frameworks. These systems, leveraging advanced algorithms rooted in machine learning, continuously scrutinize live video streams to establish a baseline of normal activities. The fundamental aim is to promptly identify deviations and anomalies, ushering in a new era of proactive and responsive security monitoring. This technology's real-time capabilities represent a transformative leap forward, enabling immediate responses to potential threats or irregular events within monitored environments. The effectiveness of real-time anomaly detection lies not only in its ability to distinguish between normal and abnormal patterns but also in its contribution to the broader landscape of safety and protection. This abstract delves into the multifaceted significance of real-time CCTV anomaly detection, exploring its role in elevating overall security measures. Beyond the immediate identification of anomalies, these systems promise to shape the future of security by offering a proactive approach to surveillance. As technological advancements persist, the integration of such systems underscores a commitment to anticipatory security strategies, ensuring adaptability in the face of evolving security challenges. Keywords: Anomaly Detection, Intrusion Detection, Machine Learning, Statistical Methods, Network Security, Cybersecurity, Pattern Recognition, Alarm Systems, Real-time Detection.

Implementation of SI-KEPPO Innovation to Increase Return Visits of Hypertension Patients at Public Health Center of Sobo, Banyuwangi

The key to managing hypertension is regular control visits to the community health center or other health facilities. These visits are critical in monitoring response to treatment, adjusting therapy if necessary, and providing education and support to the patient. Low compliance of hypertension patients with re-visits or regular control can hinder the success of hypertension management and increase the risk of complications. The SI-KEPPO (Automatic Reminder Message Group System) innovation aims to provide an effective solution in managing and arranging re-visits or reminding individuals or groups of contact time automatically via text messages or other messages. This activity is a community service aimed at doctors, nurses, administration staff and counter staff. A direct training is carried out on computers owned by the Community Health Center so that deficiencies and advantages are detected in the existing facilities at the Community Health Center. The material presented is an introduction to the program or innovation by explaining the use of the innovation, the preparations made and the procedures for implementing it. There were 1 doctor, 4 nurses, 1 medical center administration staff, 1 operator staff, and 1 counter staff who participate in community service activities. All participants were very enthusiastic about this training and it could increase the number of repeat visits for hypertensive patients.

Febrile Immunocompromised Renal Transplant Recipient with Allograft Dysfunction: Detection of an Undiagnosed Prostate Abscess by [18F]FDG-PET/CT along with Treatment Response Monitoring

AbstractThe purpose of this report is to provide a comprehensive description of a post-transplant febrile patient's clinical course, complications, surgical procedure, and long-term management including evaluation by 18F-fluorodeoxyglucose [(18F)FDG] positron-emission tomography combined with computed tomography (PET/CT). A 35-year-old male, a postrenal transplant patient, developed chronic allograft dysfunction and presented with fever with chills, with suspicion of acute-on-chronic graft dysfunction, but no infective focus localization on chest X-ray, ultrasonography (USG) whole abdomen, or blood culture. Urine microscopy showed 8 to 10 pus cells/high-power field (hpf) and culture showed Klebsiella pneumoniae and Pseudomonas aeruginosa with low colony count. Culture-sensitive antibiotics were prescribed for 2 weeks, and after 3 weeks febrile episodes relapsed, symptoms progressed, and required emergency hospitalization due to acute painful urinary retention. Proteinuria and no growth were noted in urine analysis, serum creatinine was 5.36 mg/dL, and C-reactive protein was 15.7mg/dL, and remaining parameters were unremarkable. [18F]FDG-PET/CT was considered in order to resolve diagnosis, which revealed abnormal heterogeneous tracer uptake in the enlarged prostate with hypodense areas within, suggesting prostatitis with abscess formation and pyelonephritis in the upper pole of the transplant kidney. USG kidney urinary bladder (KUB) correlation confirmed prostatic abscess and transurethral drainage done, and pus culture revealed Burkholderia pseudomallei. Culture-sensitive intravenous meropenem treatment was given for 3 weeks. At 5 weeks, follow-up [18F]FDG-PET/CT showed low metabolic residual prostate uptake, suggesting a good response with residual infection. Thus, intravenous antibiotics was changed to oral antibiotics for another 6 weeks. His symptoms completely resolved at the end of treatment; however, his graft function worsened, with serum creatinine reaching 6 to 7 mg/dL, and eventually, after 8 months he became dialysis dependent.

NIKKY THE HUMANOID ROBOT FOR HEALTHY AND SAFETY LIVING

NIKKY THE HUMANOID ROBOT FOR HEALTHY AND SAFETY LIVING

Programmed Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor and Monitor of Response to Atezolizumab plus Bevacizumab Treatment in Patients with Hepatocellular Carcinoma.

There remains no reliable biomarker of therapeutic efficacy in hepatocellular carcinoma (HCC) for the PD-L1 inhibitor atezolizumab and bevacizumab (Atezo/Bev). Circulating tumor cells (CTCs) enable the serial collection of living tumor cells. Pre-treatment and serial CTC gene expression changes and tumor histology were evaluated to identify predictors of response to Atezo/Bev. Peripheral blood from 22 patients with HCC treated with Atezo/Bev and 24 patients treated with lenvatinib was serially collected. The RNA expression in CTCs was analyzed using qRT-PCR. Higher PD-L1 expression in pre-treatment CTCs was associated with response and improved prognosis with Atezo/Bev treatment, but not with lenvatinib. There was no correlation between PD-L1 expression in CTCs and that in liver tumor biopsy specimens scored using imaging software. Furthermore, PD-L1 RNA expression in CTCs was dynamically altered by Atezo/Bev, decreasing during effective response and increasing upon progression. CTC-derived RNA collected during Atezo/Bev indicates that patients with higher PD-L1 expression in CTCs at baseline were 3.9 times more responsive to treatment. Therefore, PD-L1 RNA levels in CTCs are an accurate response predictor and may be a monitorable biomarker that changes dynamically to reflect the response during Atezo/Bev treatment.

Telemedicine in Nail Psoriasis: Validation of a New Tool to Monitor (In-Person, In-Picture, and In-Video) Nail Psoriasis Severity in Patients with Concurrent Onychophagia and Onychotillomania.

Since during the COVID-19 pandemic nail psoriasis was evaluated exclusively with teledermatology, dermatologists started to face the difficulty in rating it concurrent with other onycopathies (i.e., onychotillomania and onychophagy). Thus, we aimed to improve the existing severity scores and verify the value in different clinical settings (i.e., in person vs. teledermatology (video or picture)). This multicenter prospective observational study evaluated patients with nail psoriasis and screened them for onychophagy or onychotillomania in telemedicine from May2020 to January 2021. For therapeutic purposes patients with nail psoriasis were followed and rated with the Nijmegen-Nail psoriasis Activity Index tooL (N-NAIL) for 9months; at the same time, N-NAIL and a new dedicated index that monitor also the changes in nail dimension (Galeazzi-(G) N-NAIL) were tested for accuracy. We assessed inter- and intraobserver agreement for the three different settings (in person, video, and pictures). In our cohort of 382 patients with nail psoriasis after a clinical and dermatoscopic assessment we found 20 (5.24%) patients with onychophagy and 17 (4.45%) patients with onychotillomania. Analysis of the impact of nail psoriasis on patients revealed that onycholysis and crumbing, followed by subungual hyperkeratosis, were the clinical signs that prevalently bothered patients. N-NAIL score displayed moderate intra- and interobserver agreement. Over the 9months follow-up, N-NAIL vs. GN-NAIL displayed a solid correlation at all the examined time points, i.e., baseline and after 3, 6, and 9months. We created a new tool, the GN-NAIL capable of efficiently scoring nail psoriasis severity in complex cases, such as patients with onychotillomania and onychophagy, and monitor response to treatment during the COVID-19 pandemic.

The Role of Galectins in Asthma Pathophysiology: A Comprehensive Review

Galectins are a group of β-galactoside-binding proteins with several roles in immune response, cellular adhesion, and inflammation development. Current evidence suggest that these proteins could play a crucial role in many respiratory diseases such as pulmonary fibrosis, lung cancer, and respiratory infections. From this standpoint, an increasing body of evidence have recognized galectins as potential biomarkers involved in several aspects of asthma pathophysiology. Among them, galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-10 (Gal-10) are the most extensively studied in human and animal asthma models. These galectins can affect T helper 2 (Th2) and non-Th2 inflammation, mucus production, airway responsiveness, and bronchial remodeling. Nevertheless, while higher Gal-3 and Gal-9 concentrations are associated with a stronger degree of Th-2 phlogosis, Gal-10, which forms Charcot–Leyden Crystals (CLCs), correlates with sputum eosinophilic count, interleukin-5 (IL-5) production, and immunoglobulin E (IgE) secretion. Finally, several galectins have shown potential in clinical response monitoring after inhaled corticosteroids (ICS) and biologic therapies, confirming their potential role as reliable biomarkers in patients with asthma.

Abstract PO4-07-11: FDG-PET is superior to bone scintigraphy for the detection of bone metastases in breast cancer patients

Abstract Background: Bone is the commonest site for metastases in breast cancer patients, with up to 44% of patients having bone as their sole site of metastatic disease. Patients are at increased risk of morbidity from skeletal related events (SRE) from bone metastases due to pathological fractures and spinal cord compression. Early diagnosis is crucial so that bone modifying agents can be used to prevent SREs and other agents such as CDK4/6 inhibitors can be considered. Bone scintigraphy is the most widely performed first investigation for patients at high risk or symptomatic from bone metastases. Methods: We performed a meta-analysis comparing FDG-PET and bone scintigraphy using PubMed, Science Direct, and Embase for the literature search. 1009 patients were included in the study. Data for 2 × 2 contigency tables was selected and QUADAS-2 was used for quality assessment. Diagnostic accuracy was performed using Graph pad Prism 9.5.1 and R studio 2022. Pooled sensitivity and specificity of FDG-PET/CT was 96.6% (95% CI=91.5%-98.7%) and 96.8% (95% CI=82.1%-99.5%) respectively. Respective results for BS were 88.3% (95% CI=79.8%-93.5%) and 81.3% (95% CI=63.1%-91.7%). Sensitivity and specificity of FDG-PET/CT was significantly higher than BS (P=0.0063, P= 0.0068, respectively). The diagnostic odds ratio and area under ROC curve were significantly higher for FDG-PET/CT than BS (654.36 vs 35.24, and 0.980 vs 0.877, respectively). Conclusion: FDG-PET is superior to bone scinitigaphy for the detection of bone metastases in breast cancer.The benefits of replacing BS with FDG-PET/CT are evident. However othere technologies such as DW-MRI should be considered. Large multicentre prospective trials with strict FDG-PET/CT imaging protocols compared to DW-MRI both for disease detection and monitoring of response are required to strengthen the evidence in this field, to help inform imaging guidelines and best practices in the future. Newer technologies such as [18F]estradiol (FES)-PET and [18F]GE-226 for HER2 expression also warrant further investigation in ER positive and HER2 positive breast cancer. Citation Format: Laura Kenny, Maisher Tin-U. FDG-PET is superior to bone scintigraphy for the detection of bone metastases in breast cancer patients [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 PO4-07-11.

Abstract PO5-04-13: Liquid Biopsy Testing in a Greek Cohort of ER-positive, HER2-negative metastatic breast cancer patients

Abstract AIM Endocrine therapy (ET) represents the first line treatment for patients with ER+, HER2- breast cancer, however disease progression is observed in many cases. PIK3CA and ESR1 are the most encountered mutated genes that have been associated with targeted molecular treatment, as well as with resistance to Endocrine Therapy. Liquid biopsy is a non-invasive procedure, that can provide “real-time” monitoring of disease progression and response to treatment. The aim of this study is to determine the mutation rate of ESR1 and PIK3CA genes in a selected cohort of 200 Greek breast cancer patients, using liquid biopsies and NGS technology. PATIENTS AND METHODS Liquid biopsies were collected from 200 ER-positive, HER2-negative metastatic breast cancer patients who have received at least one previous line of endocrine treatment. cfDNA was extracted using the QIAamp Circulating Nucleic Acid Kit (Qiagen). Library preparation was performed using Oncomine™ Breast cfDNA Research Assay (Thermofisher Scientific) and sequencing was carried out using Ion GeneStudio™ S5 System (Thermofisher Scientific). Ion Torrent Oncomine Knowledgebase Reporter was used in sequence analysis and interpretation of Copy number variations, SNPs, and indels. RESULTS Preliminary data of the first 49 examined samples demonstrated the prevalence of ESR1 and PIK3CA mutations in 20.4% (10/49) and 38.7% (19/49) of the cases respectively. The most frequently mutated codon in the ESR1 gene is the Y537, while in the PIK3CA gene, the H1047 codon is mainly altered. ESR1 and PIK3CA genes were co-mutated in 10.2% of the cases. Mutations in KRAS (6.1%) and TP53 (24%) were also detected. CONCLUSION More than 20% of the ER-positive, HER2-negative breast cancer patients with metastatic disease are eligible for targeted treatment with elacestrant. In addition, the high prevalence of mutations detected in our cohort indicates that liquid biopsy NGS panel testing can be used to monitor treatment response, track the development of resistance, and identify emerging genetic alterations that may guide treatment adjustments or the selection of alternative targeted therapies in breast cancer patients. REFERENCES Demir Cetinkaya B, Biray Avci C. Molecular perspective on targeted therapy in breast cancer: a review of current status. Med Oncol. 2022 Jul 14;39(10):149. doi: 10.1007/s12032-022-01749-1. PMID: 35834030; PMCID: PMC9281252. Liao H, Huang W, Pei W, Li H. Detection of ESR1 Mutations Based on Liquid Biopsy in Estrogen Receptor-Positive Metastatic Breast Cancer: Clinical Impacts and Prospects. Front Oncol. 2020 Dec 15;10:587671. doi: 10.3389/fonc.2020.587671. PMID: 33384956; PMCID: PMC7770162. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-elacestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast-cancer Citation Format: Nikolaos Tsoulos, Angeliki Meintani, Georgios Kapetsis, Chrysiis Chatzigiannidou-Florou, Aikaterini Tsantikidi, Stella Maxouri, Eleni Thanou, Kalliopi Aggelaina, Vasiliki Metaxa-Mariatou, Georgios Tsaousis, Ioannis Natsiopoulos, Vasileios Venizelos, Christos Markopoulos, Flora Zagouri, Eleftherios Kampletsas, Eirini Karyda, Dimitrios Tryfonopoulos, Konstantinos Papazisis, Dimitrios Ziogas, Ilias Athanasiadis, Eirini Papadopoulou, Georgios Nasioulas. Liquid Biopsy Testing in a Greek Cohort of ER-positive, HER2-negative metastatic breast cancer patients [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 PO5-04-13.

Abstract PO1-15-12: Circulating tumor DNA (ctDNA) for prediction of pathologic complete response (pCR) after 12 weeks of pembrolizumab + trastuzumab + pertuzumab in HER2-enriched early breast cancer: WSG-Keyriched-1 trial

Abstract Background ctDNA testing is emerging as an important biomarker in early breast cancer (eBC). However, its value in prediction of tumor response to de-escalated, chemotherapy-free neoadjuvant therapy (NAT) remains underexplored. In WSG-Keyriched-1 (NCT03988036), a single-arm phase 2 trial, we investigated for the first time a chemotherapy-free NAT with dual HER2 blockade and pembrolizumab in HER2- enriched HER2+ eBC. In this pre-specified translational analysis, we evaluated whether ctDNA measurement could predict pCR. Methods 48 patients (pts) with HER2 2+ (ISH+) or 3+ eBC (stage I-III) and HER2-enriched subtype by PAM50 were included. Pts received pembrolizumab (200 mg), trastuzumab biosimilar (loading dose (LD) 8 mg/kg bodyweight (BW), maintenance dose (MD) 6 mg/kg BW), and pertuzumab (LD 840 mg/kg BW, MD 420 mg/kg BW) q3w for 12 weeks. Primary objective was pCR (ypT0/is ypN0). ctDNA was analyzed in 92 plasma samples collected from 31 pts at baseline (BL) and week 3 of NAT and 30 pts at end of treatment (EOT). Sequencing libraries with unique molecular identifiers were constructed from cell-free DNA and hybridization panels with ≤50 patient-specific somatic mutations from tumor sequencing were used for enrichment. Libraries were sequenced to an ultra-high depth of 100,000×. Sequencing data was analyzed using a combination of public pipelines (megSAP and umiVar2 for mapping and deduplication) and custom in-house scripts (to extract the allele counts for patient-specific variants). To reduce the error rate, only corrected reads with ≥4 duplicates were used. p-value for ctDNA detection was calculated using the total variant count, depth and sample-specific error. Association between ctDNA with pCR and other clinical parameters were assessed with Chi-square or Fisher’s exact test and univariable logistic regression. Additionally, bivariable logistic regressions for pCR were performed with ctDNA and either cT, cN, or grade. Results ctDNA was detected (ctDNA+) in 58.0% (n=18/31) of pts at BL, 9.7% (n=3/31) at week 3, and 10% (n=3/30) at EOT. ctDNA was cleared by week 3 in 83.3% of pts (n=15/18). Compared with ctDNA-negative cases (ctDNA-) at BL, those ctDNA+ more often had cT2-3 disease (94.4%, n=17/18, vs 38.5%, n=5/13; p=.001) and lymph node involvement (61.1%, n=11/18, vs 0%, n=0/13; p< .001). 72.2% (n=13/18) of ctDNA+ and 61.5% (n=8/13) of ctDNA- cases at BL were grade 3 (p=.53). Each of the 3 pts who remained ctDNA+ at week 3 was node-positive; all pts remaining ctDNA- at week 3 were node-negative. pCR rate was 38.9% (n=7/18) in ctDNA+ vs 76.9% (n=10/13) in ctDNA- pts at BL (p=.067), 0% (n=0/3) in ctDNA+ vs 60.7% (n=17/28) in ctDNA- at week 3 (p=.081), and 33.3% (n=1/3) in ctDNA+ vs 59.3% (n=16/27) in ctDNA- at EOT (p=.565). pCR rate was highest in pts who remained ctDNA- throughout week 3 (76.9%, n=10/13), compared to pts with ctDNA cleared by week 3 (46.7%, n=7/15), and pts remaining ctDNA+ (0%, n=0/3, p=.024). ctDNA at BL was predictive for pCR in univariable analysis (odds ratio, OR 0.22, 95%CI 0.04- 0.93, area under curve, AUC=0.69). Bivariable models including ctDNA and grade yielded the highest accuracy for analyses with ctDNA at BL (AUC=0.77), week 3 (AUC=0.79), and with ctDNA change from BL to week 3 (AUC=0.87). Conclusions Absence of ctDNA prior to and during NAT, as well as early clearance of ctDNA associates with a higher pCR rate in eBC pts with HER2-enriched intrinsic subtype treated with chemotherapy-free pembrolizumab plus dual HER2 blockade. These results are in line with prior data with more intensive therapy from I-SPY 2 and NeoALTTO trials in HER2+ eBC and indicate that ctDNA analysis during NAT appears feasible for real- time monitoring of response to treatment and could be used to guide escalation/de-escalation strategies. Further trials with a larger number of pts and pre-designed follow-up are needed to confirm the role of ctDNA for prediction of tumor response and relapse. Citation Format: Monika Graeser, Sherko Kuemmel, Oleg Gluz, Christopher Schroeder, Leon Schuetz, Olga Kelemen, Stephan Ossowski, Katarzyna Jozwiak, Mattea Reinisch, Athina Kostara, Iris Scheffen, Kerstin Lüdtke-Heckenkamp, Felix Hilpert, Angela Kentsch, Carsten Ziske, Reinhard Depenbusch, Michael Braun, Jens-Uwe Blohmer, Matthias Christgen, Stephan Bartels, Hans-Heinrich Kreipe, Enrico Pelz, Ulrike Nitz, Peter Schmid, Nadia Harbeck, Andreas Hartkopf. Circulating tumor DNA (ctDNA) for prediction of pathologic complete response (pCR) after 12 weeks of pembrolizumab + trastuzumab + pertuzumab in HER2-enriched early breast cancer: WSG-Keyriched-1 trial [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 PO1-15-12.

CRP/Albumin Ratio and NLR in Recognizing Critically Ill Patients

Managing critically ill patients in the emergency department requires a comprehensive approach that encompasses rapid recognition, timely intervention, and continuous monitoring. These patients present with a spectrum of conditions ranging from trauma to septic shock, necessitating immediate medical attention to prevent further deterioration. The initial assessment follows the ABCDE approach, focusing on Airway, Breathing, Circulation, Disability, and Exposure. Resuscitation and stabilization efforts aim to restore perfusion and oxygenation to vital organs through fluid resuscitation, vasopressor therapy, and mechanical ventilation. Ongoing care involves vigilant monitoring of vital signs, laboratory parameters, and organ function, guiding therapeutic interventions, and informing decisions regarding escalation or de-escalation of care. Laboratory parameters, including inflammatory markers like C-reactive protein and neutrophil-to-lymphocyte ratio, play a crucial role in assessing the patient's condition, monitoring response to treatment, and predicting clinical outcomes. Multidisciplinary collaboration ensures comprehensive care tailored to the patient's needs, ultimately optimizing outcomes and reducing mortality in this high-risk population.

Abstract PO5-16-05: Integrating Circulating Tumor Cells (CTCs) and Cell-free DNA (cfDNA) Signatures for Monitoring Treatment Response in Stage III/IV Inflammatory Breast Cancer

Abstract Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, comprising only between 1-5% of all breast cancer cases in the United States. Despite its low incidence, IBC accounts for 10% of breast cancer-related deaths and is often diagnosed with metastasis, resulting in shorter survival compared to non-IBC cases. The 5-year relative survival rate for all stages of IBC is 39%, dropping to 19% for patients with distant metastasis. Liquid biopsy-based biomarkers have emerged as potential analytes for predicting prognosis and monitoring response to therapies in IBC patients. We explored the prognostic role of liquid biopsy encompassing both CTCs and cfDNA in the blood of patients with stage III/IV IBC and their clinical outcomes. Methods: CTC and cfDNA analysis was performed on 90 blood samples from 47 patients with stage III and IV IBC. Samples were collected before (pre-treatment, n=43) initiation and after (post-treatment, n=47) completion of neoadjuvant chemotherapy. CTCs were enriched and enumerated using the CellSearch® platform (Menarini-Silicon Biosystems). CfDNA was extracted from plasma using MagMax™ Cell-Free Total Nucleic Acid Isolation Kit (Applied Biosystems™) and quantified using the Qubit™ dsDNA High Sensitivity kit (Invitrogen™). Differences in cfDNA concentrations were used to plot a receiver operating characteristic (ROC) curve which was then used to determine Area Under the Curve (AUC) and a cfDNA cut-off point. ROC cut-off was calculated based on Youden Index J. Survival analysis was performed by the Kaplan-Meier estimator and Cox regression models. P-values were measured using the Student t-test. Results: Prior to neoadjuvant treatment, CTC was detected in 51% of patient samples, and the median cfDNA concentration was 5.87 ng/mL (range 0.95-24.11 ng/mL). After completion of neoadjuvant treatment, CTC was detected in 25% of patient samples, and the median cfDNA concentration was 11.19 ng/mL (range 3.41-88.13 ng/mL). The cut-off points determined for pre-treatment and post-treatment cfDNA concentration was >4.2 ng/mL and >9.5 ng/mL respectively. At pre-treatment, CTC detection and cfDNA concentration >4.2 ng/mL were independently associated with disease relapse (P=0.007, 0.016, respectively). The combination of CTC detection and cfDNA concentration >4.2 ng/mL was significantly associated with disease relapse (P=0.0004), decreased relapse free survival (RFS, P=0.005) and overall survival (OS, P=0.007). At the post-neoadjuvant treatment time point, the combination of CTC detection and cfDNA concentration >9.5 ng/mL was significantly associated with relapse regardless of pCR status (P=0.02). Conclusion: The combined presence of CTCs and elevated cfDNA concentrations in patients with stage III/IV IBC after completion of neoadjuvant chemotherapy was associated with disease relapse regardless of pCR status. A combination of elevated cfDNA and CTC detection signatures after completion of neoadjuvant chemotherapy may be useful for risk stratification and adjuvant systemic therapy planning. Citation Format: Sridevi Addanki, Salyna Meas, Vanessa Sarli, Abdulkader Almosa, Wendy Woodward, Dhruvajyoti Roy, Anthony Lucci. Integrating Circulating Tumor Cells (CTCs) and Cell-free DNA (cfDNA) Signatures for Monitoring Treatment Response in Stage III/IV Inflammatory 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 PO5-16-05.

Kidney Doppler Ultrasonography in Critical Care Nephrology.

Color pulsed-wave Doppler ultrasound (CPWD-US) emerges as a pivotal tool in intensive care units (ICUs) for diagnosing acute kidney injury (AKI) swiftly and non-invasively. Its bedside accessibility allows for rapid assessments, making it a primary imaging modality for AKI characterization. Furthermore, CPWD-US serves as a guiding instrument for key diagnostic-interventional procedures such as renal needle biopsy and percutaneous nephrostomy, while also facilitating therapy response monitoring and AKI progression tracking. This review shifts focus towards the integration of renal ultrasound into ICU workflows, offering contemporary insights into its utilization through a diagnostic-standard-oriented approach. By presenting a flow chart, this review aims to provide practical guidance on the appropriate use of point-of-care ultrasound (POC-US) in critical care scenarios, enhancing diagnostic precision, patient management, and safety, albeit amidst a backdrop of limited evidence regarding long-term outcomes.

Abstract PO5-13-12: Personalized circulating tumor DNA testing for recurrence detection and treatment response monitoring in patients with metastatic invasive lobular carcinoma

Abstract Introduction Metastatic invasive lobular carcinoma (mILC) presents unique challenges during treatment response monitoring. A higher frequency of metastases to the bone, gastrointestinal tract, uterus, meninges, ovary, and diffuse serosal involvement is observed in mILC. The challenge with mILC is that they can be difficult to detect clinically and radiographically, and consequently clinical progression can be difficult to determine with conventional imaging modalities like CT Scans, thus precluding many patients with mILC from enrolling into clinical trials. Therefore more accurate biomarkers are needed to better assess response to treatment in real time. In this study, we demonstrate the feasibility of longitudinal ctDNA testing for treatment response monitoring in patients with mILC. Methods In this real-world study, longitudinal plasma samples (n=219) from 60 patients with mILC, treated across 52 independent clinics between 7/22/21 and 6/15/23, were analyzed. A personalized, tumor-informed ctDNA assay (SignateraTM bespoke, mPCR-NGS assay) was used for detection and quantification of ctDNA in plasma samples. Results In this cohort, the median patient age at diagnosis of metastatic disease (baseline) was 62.9 years (range: 32.2-79.7). Of the 60 patients, 41 (68%) had ER+PR+HER2-, 7 (12%) ER+PR-HER2-, 4 (7%) ER+PR+HER2+, 2 (3%) ER+PR-HER2+, 1 (2%) triple negative breast cancer; receptor status was not available for 5 (8%) patients. CDH1 (75%) and PIK3CA (42%) were observed to be the top two genes with somatic, nonsynonymous mutations. Mutations in TP53 and TBX3 were observed in 13% of patients, mutations in AKAP9, IGFN1, RBM26, and RFC3 in 10% of patients, and mutations in ESR1 in 6.7% of patients. At variant level, PIK3CA p.H1047R (22%) and RBM26 p.Q701Tfs*23 (10%) were the top two somatic variants identified. The most common CDH1 variant, p.Q23*, was found in 5% of the cases. Of the 60 patients, 37 (61.7%) were ctDNA-positive at all time points while on treatment (chemotherapy/endocrine therapy/targeted therapy) with the first time point collected at a median of 6.7 months (range: 2.5-2307 months) from baseline. Of these 37, imaging/biopsy results after baseline were available for 32 patients, 86% (27/32) of whom progressed. Thirty-two of 37 persistently ctDNA-positive patients had serial ctDNA measurements available, of which 14 (43%) had significant increase in ctDNA levels (average: 47-fold increase, standard deviation: 98) from first to last time points. At some point during their care ctDNA was detectable in all (n=51) patients with evidence of clinical progression. Of the 60 patients, 14 (23.3%) were ctDNA-negative at all time points tested. None of the 14 persistently ctDNA-negative patients had evidence of disease recurrence or progression at the time of initial testing or throughout ctDNA monitoring. The first ctDNA time point was collected at a median of 33.1 months (range: 0.68-92 months) from baseline for these patients,a median of 3 time points was tested per patient (1-12). Of the remaining 9/60 patients, 3 (33%) had sustained ctDNA clearance for a median of 46 days (range: 0-224 days) in response to treatment, and 2 (22%) were initially ctDNA-negative but turned positive 105 and 156 days later, indicating potential resistance to treatment and molecular progression. Additional 4/9 (44%) had ctDNA levels consistently low levels (average: 0.42 mean tumor molecules/mL) while on treatment for a median of 260 days (range: 217-442) and showed no evidence of progression. Conclusions ctDNA status and dynamics correlate well with clinical status of patients with mILC, as determined by conventional monitoring tools such as imaging and biopsy. Our results indicate that personalized, tumor-informed, longitudinal ctDNA testing may serve as a useful tool for detection of progression and monitoring treatment response in mILC patients. Citation Format: Steffi Oesterreich, Antony Tin, Samuel Rivero-Hinojosa, Janie Fielder, Jenifer Ferguson, Ekaterina Kalashnikova, Angel Rodriguez, Minetta Liu, Adrian Lee. Personalized circulating tumor DNA testing for recurrence detection and treatment response monitoring in patients with metastatic invasive lobular carcinoma [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 PO5-13-12.

Amoebic liver abscess in an adult Nigerian: A case report

Background: Amoebic liver abscess (ALA) is a parasitic infection caused by Entamoeba histolytica. ALA is a significant health concern, particularly in regions with poor sanitation and hygiene practices. Radiological imaging plays a crucial role in the diagnosis and management of ALA. Methods: We present a case report of a 40-year-old male patient with ALA. The patient presented to a radio diagnostic centre in Umuahia with right upper quadrant abdominal pain, fever,diarrhea and weight loss. Radiological evaluation was performed using abdominal ultrasound and contrast-enhanced CT scan. The imaging findings were correlated with clinical presentation and laboratory investigations. Results: The radiological findings revealed a focal hypoechoic lesion in the right hepatic lobe with ill-defined margins and internal echoes suggestive of liquefaction. The contrast-enhanced CT scan confirmed the presence of a well-defined, hypodense lesion with peripheral enhancement and central hypoattenuation. No evidence of biliary ductal dilatation or vascular invasion was observed. Based on the findings, a diagnosis of ALA was made, and the patient was initiated on intravenous metronidazole therapy. Follow-up imaging demonstrated a decrease in abscess size and resolution of internal echoes, indicating a positive response to treatment. Conclusion: Radiological imaging, including ultrasound and CT scan, plays a pivotal role in the diagnosis and management of ALA. The characteristic imaging findings, such as hypoechoic lesions with internal echoes and peripheral enhancement with central hypoattenuation, aid in differentiating ALA from other hepatic lesions. Early diagnosis and prompt initiation of appropriate therapy are crucial for favorable patient outcomes. Radiological follow-up allows monitoring of treatment response and guides further management decisions.

Development and assessment of a multiepitope synthetic antigen for the diagnosis of Dengue virus infection

Immunodiagnostic tests for detecting dengue virus infections encounter challenges related to cross-reactivity with other related flaviviruses. Our research focuses on the development of a synthetic multiepitope antigen tailored for dengue immunodiagnostics. Selected dengue epitopes involved structural linearity and dissimilarity from the proteomes of Zika and Yellow fever viruses which served for computationally modeling the three-dimensional protein structure, resulting in the design of two proteins: rDME-C and rDME-BR. Both proteins consist of seven epitopes, separated by the GPGPG linker, and a carboxy-terminal 6 × -histidine tag. The molecular weights of the final proteins rDME-C and rDME-BR are 16.83 kDa and 16.80 kDa, respectively, both with an isoelectric point of 6.35. The distinguishing factor between the two proteins lies in the origin of their epitope sequences, where rDME-C is based on the reference dengue proteome, while rDME-BR utilizes sequences from prevalent Dengue genotypes in Brazil from 2008 to 2019. PyMol analysis revealed exposure of epitopes in the secondary structure. Successful expression of the antigens was achieved in soluble form and fluorescence experiments indicated a disordered structure. In subsequent testing, rDME-BR and rDME-C antigens were assessed using an indirect Elisa protocol against Dengue infected serum, previously examined with a commercial diagnostic test. Optimal concentrations for antigens were determined at 10 µg/mL for rDME-BR and 30 µg/mL for rDME-C, with serum dilutions ranging from 1:50 to 1:100. Both antigens effectively detected IgM and IgG antibodies in Dengue fever patients, with rDME-BR exhibiting higher sensitivity. Our in-house test showed a sensitivity of 77.3 % and 82.6 % and a specificity of 89.4 % and 71.4 % for rDME-C and rDEM-BR antigens. No cross-reactivity was observed with serum from Zika-infected mice but with COVID-19 serum samples. Our findings underscore the utility of synthetic biology in crafting Dengue-specific multiepitope proteins and hold promise for precise clinical diagnosis and monitoring responses to emerging Dengue vaccines.