Individualized Treatment Plans Research Articles

Abstract 4413: Identifying genome-wide histone profiles in patient derived models of AML for predictive biomarker development

Abstract Acute myeloid leukemia (AML) is a complex disease with highly individualized treatment plans for patients. Mostly these are based on genetic and phenotypic markers of the disease, but the patient’s overall condition is playing a significant role as well. To develop innovative drugs for a broad patient cohort, it is essential to understand the biological implications of these differences and to model them preclinically. In this study, we are assessing the utility of EpiCypher’s CUT&Tag-FFPE platform to characterize the epigenome of AML PDX samples. CUT&Tag-FFPE is an epigenome profiling assay that is compatible with Formalin-Fixed Paraffin-Embedded (FFPE) samples, enabling robust genome-wide profiling of histone modifications from limited clinical samples. We derived PDX model LEXFAM 2799 (NPM1 wt; FLT3 wt, t(8;21)) and LEXFAM 2966 (NPM1 mut; FLT3 wt) from treatment naïve patients and established in immunocompromised NSG mice. LEXFAM 2799 is a fast-growing model with passaging times of 33 days, whereas LEXFAM 2966 displays a passaging time of 140 days. We next treated with Standard of Care (SoC) agents Decitabine, Cytarabine and all-trans-retinoic acid (ATRA): LEXF 2966 was highly sensitive towards Decitabine leading to complete remission. Cytarabine induced a partial remission and ATRA had only minor effect on tumor growth. In contrast LEXFAM 2799 was resistant towards treatment with ATRA and showed only partial remission under treatment with Cytarabine or Decitabine. Using the CUT&Tag-FFPE platform we are analyzing FFPE slides from the above mentioned two AML PDX models to investigate differences in the genome-wide histone profile that relate to the different growth behavior as well as sensitivity towards SoC treatment. The goal of these studies is to identify tumor model specific profiles that correlated specifically with the sensitivity towards the hypomethylating agent Decitabine. In addition, we plan to analyze additional untreated as well as treated AML PD models to validate the identified signatures confirming them as predictive biomarkers for sensitivity towards current standard of care and prospectively as well innovative compounds. Citation Format: Alysha Simmons, Eva Oswald, Georg Kuales, Michael Keogh, Vishnu U. Kumary, Eva Brill, Martis W. Cowles, Bryan Venters, Julia B. Schueler. Identifying genome-wide histone profiles in patient derived models of AML for predictive biomarker development [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 4413.

Prediction of pCR based on clinical-radiomic model in patients with locally advanced ESCC treated with neoadjuvant immunotherapy plus chemoradiotherapy.

The primary objective of this research is to devise a model to predict the pathologic complete response in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT). We retrospectively analyzed data from 60 ESCC patients who received nICRT between 2019 and 2023. These patients were divided into two cohorts: pCR-group (N = 28) and non-pCR group (N = 32). Radiomic features, discerned from the primary tumor region across plain, arterial, and venous phases of CT, and pertinent laboratory data were documented at two intervals: pre-treatment and preoperation. Concurrently, related clinical data was amassed. Feature selection was facilitated using the Extreme Gradient Boosting (XGBoost) algorithm, with model validation conducted via fivefold cross-validation. The model's discriminating capability was evaluated using the area under the receiver operating characteristic curve (AUC). Additionally, the clinical applicability of the clinical-radiomic model was appraised through decision curve analysis (DCA). The clinical-radiomic model incorporated seven significant markers: postHALP, ΔHB, post-ALB, firstorder_Skewness, GLCM_DifferenceAverage, GLCM_JointEntropy, GLDM_DependenceEntropy, and NGTDM_Complexity, to predict pCR. The XGBoost algorithm rendered an accuracy of 0.87 and an AUC of 0.84. Notably, the joint omics approach superseded the performance of solely radiomic or clinical model. The DCA further cemented the robust clinical utility of our clinical-radiomic model. This study successfully formulated and validated a union omics methodology for anticipating the therapeutic outcomes of nICRT followed by radical surgical resection. Such insights are invaluable for clinicians in identifying potential nICRT responders among ESCC patients and tailoring optimal individualized treatment plans.

Poor short-term outcomes for prognostic high-risk patients with chronic limb-threatening ischemia undergoing endovascular therapy

BackgroundThe prognosis of chronic limb-threatening ischemia (CLTI) is poor, with an expected life expectancy of 2 or more years, which significantly influences treatment decisions. However, death may occur at the early stages of treatment for wound healing, and aggressive treatment may limit the quality of life of such patients. In patients with CLTI undergoing endovascular therapy (EVT), the Wound, Ischemia, and foot Infection (WIfI) clinical stage, male sex, older age, non-ambulatory status, low body mass index, and dialysis have been reported as predictors of mortality risk. However, most studies have not fully investigated the WIFI clinical stage as a prognostic predictor of CLTI. This study aimed to evaluate short-term prognosis and wound healing rates using the prognostic predictors (PPs) indicated above in risk-stratified patients with CLTI who underwent EVT.MethodsThis retrospective single-center observational study included 61 CLTI patients undergoing EVT from April 2020 to October 2022. The patients were divided into a high-risk group (PPs ≥ 4, n = 20) and low-risk group (PPs ≤ 3, n = 41) according to the number of PPs. Survival and wound healing rates within one year were compared between these two groups.ResultsThe mean age of the patients was 74.7 ± 1.6 years, and 42 (68.9%) were male. Among these patients, the high-risk group compared with the low-risk group had a significantly worse survival rate within one year (46.4% vs. 84.7%, log-rank p < 0.001). Fifteen patients died within one year. Of these, seven deaths were cardiovascular deaths and six were deaths from infectious diseases. Cox proportional hazards analysis showed that WIfI clinical stage 4 (p = 0.043, hazard ratio [HR] = 4.85) and the male sex (p = 0.037, HR = 6.34) influenced the prognosis of this population. The high-risk group tended to have a worse wound healing rate within one year than that had by the low-risk group (55.4% vs. 83.0%, log-rank p = 0.086).ConclusionsThe assessment of short-term prognosis and wound healing rates using PPs may be useful. Discussing the results of short-term clinical outcome assessments with patients should be considered when determining their individualized treatment plans.

Thickness of melanocytes in giant congenital melanocytic nevus for complete surgical excision: clinicopathological evaluation of 117 lesions according to the area and size

BackgroundGiant congenital melanocytic nevi (GCMN) are usually defined as nevi that exceed 20 cm in maximal diameter or 15% of the total body surface area. There have been reports of life-long malignant change risks arising from GCMN, leading to surgical excision of GCMN. This study aims to evaluate the thickness of melanocytes based on clinical factors in order to provide objective information for the complete resection of the lesion.MethodsOverall, 75 patients diagnosed with GCMN between 2000 and 2021 were included, and their clinical records were collected retrospectively. 117 pathologic slides obtained during excision were reviewed to measure nevus thickness. Clinical factors were assessed with a generalized estimated equation model for association with nevus thickness.ResultsThe thickness of nevus was significantly associated with the location and size. Nevus thickness was more superficial in the distal extremity than in the head and trunk (P = 0.003 [head]; P < 0.001 [trunk]; P = 0.091 [Proximal extremity]). Nevi sized 60 cm or more were significantly deeper than those measuring 20–29.9 cm (P = 0.035). An interaction between size and location existed (P < 0.001). Trunk and distal extremity lesions consistently exhibited uniform thickness regardless of lesion size, whereas head and proximal extremity lesions showed variations in thickness based on lesion size.ConclusionGCMNs have differences in thickness according to location and size. Therefore, it is necessary to devise an approach optimized for each patient to treat GCMN.Mini-abstractIn the study, it was emphasized that the thickness of GCMN is correlated with clinical factors, specifically the location and size of the nevus. Consequently, these findings underscore the need for individualized treatment plans for effective surgical intervention.

Experiences with telemedicine-based follow-up of chronic conditions: the views of patients and health personnel enrolled in a pragmatic randomized controlled trial

BackgroundTelemedicine is often promoted as a possible solution to some of the challenges healthcare systems in many countries face, and an increasing number of studies evaluate the clinical effects. So far, the studies show varying results. Less attention has been paid to systemic factors, such as the context, implementation, and mechanisms of these interventions.MethodsThis study evaluates the experiences of patients and health personnel enrolled in a pragmatic randomized controlled trial comparing telemedicine-based follow-up of chronic conditions with usual care. Patients in the intervention group received an individual treatment plan together with computer tablets and home telemonitoring devices to report point-of-care measurements, e.g., blood pressure, blood glucose or oxygen saturation, and to respond to health related questions reported to a follow-up service. In response to abnormal measurement results, a follow-up service nurse would contact the patient and consider relevant actions. We conducted 49 interviews with patients and 77 interviews with health personnel and managers at the local centers. The interview data were analyzed using thematic analysis and based on recommendations for conducting process evaluation, considering three core aspects within the process of delivering a complex intervention: (1) context, (2) implementation, and (3) mechanisms of impact.ResultsPatients were mainly satisfied with the telemedicine-based service, and experienced increased safety and understanding of their symptoms and illness. Implementation of the service does, however, require dedicated resources over time. Slow adjustment of other healthcare providers may have contributed to the absence of reductions in the use of specialized healthcare and general practitioner (GP) services. An evident advantage of the service is its flexibility, yet this may also challenge cost-efficiency of the intervention.ConclusionsThe implementation of a telemedicine-based service in primary healthcare is a complex process that is sensitive to contextual factors and that requires time and dedicated resources to ensure successful implementation.Trial registrationThe trial was registered in www.clinicaltrials.gov (NCT04142710). Study start: 2019-02-09, Study completion: 2021-06-30, Study type: Interventional, Intervention/treatment: Telemedicine tablet and tools to perform measurements. Informed and documented consent was obtained from all subjects and next of kin participating in the study.

Health-related quality of life and its determinants among cancer patients: evidence from 12,148 patients of Indian database

BackgroundCancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants.MethodsData were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics.ResultsMajority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45–60 years and females (49.3–58.3%). Most patients were found to be in stage III (40–40.6%) or stage IV (29.4–37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771).ConclusionOlder age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.

Interventional Management of Low Back Pain: A Comprehensive Review of Epidural Steroid Injections and Related Techniques

Lower back pain (LBP) represents a significant global health burden, impacting individuals’ quality of life, productivity, and financial stability. While acute episodes may resolve spontaneously, chronic LBP persists beyond 12 weeks, necessitating a multidisciplinary approach to management. This comprehensive review examines the interventional management of LBP, with a focus on Epidural Steroid Injections (ESIs) and related techniques. ESIs, administered into the epidural space surrounding spinal nerves, aim to alleviate inflammation and nerve compressioninduced pain. However, they carry inherent risks, including infection, nerve damage, and allergic reactions. Comparative effectiveness studies highlight varying outcomes associated with different interventions, emphasizing the need for individualized treatment plans. Guidelines from professional organizations advocate for a patient-centered approach, prioritizing non-pharmacologic therapies as first-line treatments. Integrating evidence-based practices and considering patient preferences and clinical circumstances are crucial in optimizing outcomes. This review also discusses patient selection criteria, safety considerations, and long-term outcomes associated with interventional management techniques. By adhering to established guidelines and integrating a range of therapeutic options, clinicians can effectively address the multifaceted challenges posed by LBP, ultimately enhancing patient well-being, and improving treatment outcomes. A holistic approach, encompassing both conservative and interventional modalities, is essential in the comprehensive management of LBP

Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

A Review on Patient-Derived 3D Micro Cancer Approach for Drug Screen in Personalized Cancer Medicine.

Precision medicine in oncology aims to identify an individualized treatment plan based on genomic alterations in a patient's tumor. It helps to select the most beneficial therapy for an individual patient. As it is now known that no patient's cancer is the same, and therefore, different patients may respond differently to conventional treatments, precision medicine, which replaces the one-size-fits-all approach, supports the development of tailored treatments for specific cancers of different patients. Patient-specific organoid or spheroid models as 3D cell culture models are very promising for predicting resistance to anti-cancer drugs and for identifying the most effective cancer therapy for high-throughput drug screening combined with genomic analysis in personalized medicine. Because tumor spheroids incorporate many features of solid tumors and reflect resistance to drugs and radiation, as in human cancers, they are widely used in drug screening studies. Testing patient-derived 3D cancer spheroids with some anticancer drugs based on information from molecular profiling can reveal the sensitivity of tumor cells to drugs and provide the right compounds to be effective against resistant cells. Given that many patients do not respond to standard treatments, patient-specific treatments will be more effective, less toxic. They will affect survival better compared to the standard approach used for all patients.

An in-silico planning study of stereotactic body radiation therapy for polymetastatic patients with more than ten extra-cranial lesions

Background and purposeLimited data is available about the feasibility of stereotactic body radiation therapy (SBRT) for treating more than five extra-cranial metastases, and almost no data for treating more than ten. The aim of this study was to investigate the feasibility of SBRT in this polymetatstatic setting. Materials and methodsConsecutive metastatic melanoma patients with more than ten extra-cranial metastases and a maximum lesion diameter below 11 cm were selected from a single-center prospective registry for this in-silico planning study. For each patient, SBRT plans were generated to treat all metastases with a prescribed dose of 5x7Gy, and dose-limiting organs (OARs) were analyzed. A cell-kill based inverse planning approach was used to automatically determine the maximum deliverable dose to each lesion individually, while respecting all OARs constraints. ResultsA total of 23 polymetastatic patients with a medium of 17 metastases (range, 11–51) per patient were selected. SBRT plans with sufficient target coverage and respected OARs dose constraints were achieved in 16 out of 23 patients. In the remaining seven patients, the lungs V5Gy < 80 % and the liver D700 cm3 < 15Gy were most frequently the dose-limiting constraints. The cell-kill based planning approach allowed optimizing the dose administration depending on metastases total volume and location. ConclusionThis retrospective planning study shows the feasibility of definitive SBRT for 70% of polymetastatic patients with more than ten extra-cranial lesions and proposes the cell-killing planning approach as an approach to individualize treatment planning in polymetastatic patients’.

Trajectories of Daily Postconcussion Symptoms in Children.

To identify trajectories of daily postconcussion symptoms (PCS) from the acute postinjury period to symptom resolution among concussed children and examine demographic factors and acute PCS associated with the identified symptom trajectories. Seventy-nine participants with a concussion were enrolled within 72 hours of injury and completed a daily survey that assessed PCS from enrollment until symptom resolution. This was a prospective cohort study among concussed children aged 11-17 years. Children rated their concussion symptoms daily using the Post-Concussion Symptom Scale. Symptom duration was assessed using participants' date of symptom resolution and coded as a dichotomous variable: (1) PCS duration 14 days or less or (2) PCS duration longer than 14 days. Of the 79 participants, most were male ( n = 53, 67%), injured during a sporting activity ( n = 67, 85%), or had PCS that persisted for more than 14 days post-injury ( n = 41, 52%). Group-based trajectory modeling yielded 4 trajectory groups: (1) low acute/resolved PCS ( n = 39, 49%), (2) moderate/persistent PCS ( n = 19, 24%), (3) high acute/persistent PCS ( n = 13, 16%), and (4) high acute/resolved PCS ( n = 8, 10%). No significant associations were found between demographic factors and the trajectory group. A higher symptom burden at injury was associated with an increased odds of being in the high acute/resolved or high acute/persistent recovery groups than being in the low acute/resolved group (odds ratio [OR] 1.39, 95% CI = 1.11-1.74; OR = 1.33, 95% CI = 1.11-1.60, respectively), as was a higher symptom severity at injury (OR = 1.09, 95% CI = 1.03-1.15; OR = 1.06, 95% CI = 1.02-1.11, respectively). Our findings may help clinicians identify concussed children on slower recovery trajectories, and implement early, individualized treatment plans that foster optimal recovery for concussed children.

Advancements in keratoplasty: Exploring newer techniques and imaging modalities for enhanced surgical outcomes

Abstract: Keratoplasty, the transplantation of corneal tissue, is a well-established surgical procedure for the treatment of various corneal diseases. Over the years, advancements in keratoplasty techniques have significantly improved surgical outcomes and patient satisfaction. This review article provides an overview of newer techniques and imaging modalities in keratoplasty that have emerged as promising options for corneal transplantation. The article begins with a brief overview of traditional keratoplasty techniques, including penetrating keratoplasty, deep anterior lamellar keratoplasty, Descemet’s stripping automated endothelial keratoplasty (EK), and Descemet’s membrane EK. It then delves into the discussion of newer techniques, including femtosecond laser-assisted keratoplasty, Bowman layer transplantation, and the role of anterior segment optical coherence tomography in keratoplasty. This review article aims to provide ophthalmologists with a comprehensive understanding of the newer techniques in keratoplasty, their advantages, limitations, and clinical outcomes. It emphasizes the importance of individualized treatment planning, considering patient-specific factors, and utilizing advanced imaging modalities to optimize surgical outcomes. The incorporation of newer techniques and imaging modalities in keratoplasty has the potential to revolutionize the field, offering improved visual outcomes, reduced complications, and enhanced patient satisfaction. Continued research and technological advancements will further refine these techniques, paving the way for the future of keratoplasty and improving the quality of life for patients with corneal diseases. We evaluate the currently available literature in this article to provide a comprehensive overview of contemporary surgical and imaging methods in ophthalmology to facilitate additional developments in the field of corneal transplantation.

Development of machine learning-based malignant pericardial effusion-related model in breast cancer: Implications for clinical significance, tumor immune and drug-therapy

BackgroundMalignant pericardial effusion (MPE) is a common complication of advanced breast cancer (BRCA) and plays an important role in BRCA. This study is aims to construct a prognostic model based on MPE-related genes for predicting the prognosis of breast cancer. MethodsThe BRCA samples are analyzed based on the expression of MPE-related genes by using an unsupervised cluster analysis method. This study processes the data by least absolute shrinkage and selection operator and multivariate Cox analysis, and uses machine learning algorithms to construct BRCA prognostic model and develop web tool. ResultsBRCA patients are classified into three clusters and a BRCA prognostic model is constructed containing 9 MPE-related genes. There are significant differences in signature pathways, immune infiltration, immunotherapy response and drug sensitivity testing between the high and low-risk groups. Of note, a web-based tool (http://wys.helyly.top/cox.html) is developed to predict overall survival as well as drug-therapy response of BRCA patients quickly and conveniently, which can provide a basis for clinicians to formulate individualized treatment plans. ConclusionThe MPE-related prognostic model developed in this study can be used as an effective tool for predicting the prognosis of BRCA and provides new insights for the diagnosis and treatment of BRCA patients.

Deciphering the Digital Healthscape: Unveiling the Intricacies of the Internet of Medical Things (IoMT)

Through the integration of networking, data analytics, and medical devices, the Internet of Medical Things (IoMT) has revolutionized patient care and healthcare administration. Presented here is extensive study on IoMT that sheds light on its impact on healthcare settings, including its origins, technical foundations, uses, security worries, interoperability problems, and potential future developments. The evolution of IoMT began with the integration of internet connection with medical devices and continues with the complex and linked environment of today. This shift in thinking makes possible preventative healthcare, individualized treatment plans, and remote patient monitoring. Technologies for data storage, networking, and sensors are the backbone of IoMT. Streamlined connection, real-time data transmission, and a robust IoMT architecture for healthcare applications are all described in the article. Remote patient monitoring and the management of chronic illnesses are two areas where IoMT finds application in healthcare. Literature show how IoMT describes a data-driven, proactive, and personalized healthcare delivery strategy that improves patient outcomes, treatment adherence, and resource utilization. The research addresses important topics related to IoMT, such as healthcare privacy and security. Securing IoMT and bolstering trust in connected healthcare are the goals of research into encryption, access controls, and data protection regulations. To implement IoMT, interoperability concerns must be addressed. The essay delves into the difficulties of integrating IoMT devices and systems, as well as the necessity of standardized frameworks to facilitate data sharing and interoperability. Future advances in the IoMT, such as the integration of AI and blockchain for security, are predicted in the research. The paper highlights the potential of IoMT to impact healthcare delivery and address global healthcare concerns. This study demonstrates the transformation of IoMT to academics, healthcare professionals, and policymakers. Keyword :Internet of Medical Things (IoMT), Digital Healthscape, Remote Patient Monitoring, Data Analytics, Security, Interoperability, Future Trends

Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination

Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect light dose (light fluence) at the abscess wall and PDT response. This study simulated PDT treatment planning for 13 subjects that received optical spectroscopy prior to clinical PDT, to determine the impact of measured optical properties on ability to achieve fluence rate targets in 95% of the abscess wall. Retrospective treatment plans were evaluated for 3 conditions: (1) clinically delivered laser power and assumed, homogeneous optical properties, (2) clinically delivered laser power and measured, homogeneous optical properties, and (3) with patient-specific treatment planning using measured, homogeneous optical properties. Treatment plans modified delivered laser power, intra-cavity Intralipid (scatterer) concentration, and laser fiber type. Using flat-cleaved laser fibers, the proportion of subjects achieving 95% abscess wall coverage decreased significantly relative to assumed optical properties when using measured values for 4 mW cm−2 (92% versus 38%, p = 0.01) and 20 mW cm−2 (62% versus 15%, p = 0.04) thresholds. When measured optical properties were incorporated into treatment planning, the 4 mW cm−2 target was achieved for all cases. After treatment planning, optimal Intralipid concentration across subjects was 0.14 ± 0.09%, whereas 1% was used clinically. Required laser power to achieve the 4 mW cm−2 target was significantly correlated with measured abscess wall absorption (ρ = 0.7, p = 0.008), but not abscess surface area (ρ = 0.2, p = 0.53). When using spherical diffuser fibers for illumination, both optimal Intralipid concentration (p = 0.0005) and required laser power (p = 0.0002) decreased compared to flat cleaved fibers. At 0% Intralipid concentration, the 4 mW cm−2 target could only be achieved for 69% of subjects for flat-cleaved fibers, compared to 100% for spherical diffusers. Based on large inter-subject variations in optical properties, individualized treatment planning is essential for abscess photodynamic therapy. (Clinical Trial Registration: The parent clinical trial from which these data were acquired is registered on ClinicalTrials.gov as ‘Safety and Feasibility Study of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities,’ with ClinicalTrials.gov identifier NCT02240498).

Serotonin transporter imaging agent as a probe for β-cells of pancreas

ObjectiveDiabetes mellitus (DM) is one of the major diseases in the world. Nuclear medicine imaging may be able to detect functional status of pancreatic β cells in vivo, which might elucidate the pathological mechanisms of diabetes and develop individualized treatment plans. In this study, we evaluated the ability of [125I]ADAM, a serotonin transporter (SERT) imaging agent, as a probe for detecting pancreatic β-cell mass (BCM). MethodsIn vitro cell studies were evaluated in INS-1 cells (rat islet β cell line). Biodistribution studies were performed in male normal Sprague-Dawley rats and alloxan-induced type 1 diabetes mellitus (T1DM) rats. Distribution and expression of SERT protein in pancreas of rats were also measured by immunofluorescence staining and Western blot. ResultsIn vitro cell studies showed that the concentration of [125I]ADAM associated with the INS-1 cells was increased gradually with incubation time, and the SERT specific inhibitor, escitalopram, exhibited the inhibitory effect on this interaction. Biodistribution studies also showed that the uptake of [125I]ADAM in the pancreas of normal rats was decreased in the presence of escitalopram. However, in the T1DM rat model with a significant β cells reduction, the uptake of pancreas was increased when compared with the control. Through immunofluorescence staining and Western blot, it was found that both the endocrine and exocrine cells of the normal pancreas expressed SERT protein, and the level of SERT protein in the exocrine cells was higher than islets. In the diabetic state, the expression of SERT in the exocrine cells was further increased. ConclusionsThe SERT imaging agent, [125I]ADAM, at the present form will not be suitable for imaging β cells, specifically because there were extraordinarily high non-specific signals contributing from the exocrine cells of pancreas. In addition, we noticed that the level of SERT expression was abnormally elevated in the diabetic state, which might provide an unexpected target for studying the pathological mechanisms of diabetes.

Clinical characteristics and pregnancy outcome analysis of 20 cases of acute pancreatitis during pregnancy.

This study investigated the clinical characteristics and pregnancy outcomes of acute pancreatitis during pregnancy (APIP). A retrospective analysis was conducted on 20 cases of APIP admitted to Hubei Maternal and Child Health Hospital from January 2017 to September 2021. The etiology, clinical manifestations, and perinatal outcomes of APIP were analyzed using descriptive statistical analysis of the collected data. The incidence of APIP in our hospital was 20 (0.02%) cases, all of which occurred in the late stage of pregnancy. Hypertriglyceridemic acute pancreatitis (HTG-AP) was the primary cause of APIP in 10 (50.0%) patients. A total of 11 (55.0%), seven (35.0%) and two (10.0%) patients had mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), respectively. Pregnant women with HTG-AP had significantly elevated serum triglyceride levels, had higher prepregnancy body mass indices, were more prone to developing diabetes and were more likely to progress to SAP. With a multidisciplinary approach and individualized treatment plans, there were no maternal deaths, and fetal death only occurred in one (5.0%) case. HTG-AP is prone to advancing to more severe states, and it is becoming more common every year. Therefore, blood lipid management during pregnancy should be emphasized. Pregnant women with digestive symptoms or severe hyperlipidaemia should be screened for APIP in a timely manner and receive clinical intervention to improve maternal and fetal outcomes during the perinatal period.

New advances in the treatment and diagnosis of hypertension in primary care: a literature review

Background: Despite the availability of safe and effective antihypertensive drugs, hypertension continues to be a major risk factor for cardiovascular death and morbidity worldwide. This review explores the contemporary landscape of advances in hypertension (HTN) diagnosis and treatment, examining the discordant diagnostic thresholds proposed by American and European guidelines. Methods: An integrative approach was employed, analyzing pertinent literature from sources such as ScienceDirect, Google Scholar, and PubMed. Inclusion criteria encompassed studies on new advances in HTN diagnosis and treatment in primary care, published in English within the last five years (2018-2023). Results: Diagnostic innovations focus on the preference for automated sphygmomanometers and technological advancements, enhancing precision and reliability. Treatment advancements span neurovascular dimensions, including neuromodulation, and innovations in the renin-angiotensin-aldosterone system, showcasing promising drugs like finerenone and esaxerenone. Sodium-glucose cotransporter-2 inhibitors demonstrate efficacy beyond antidiabetic effects. The complexities of renal denervation and its challenges are scrutinized, emphasizing the need for further research. Clinical decision-making underscores risk stratification, lifestyle modifications, and the emerging use of single-pill combinations and individualized treatment plans. Conclusion: The review highlights the multidimensional approach required for optimal HTN management in primary care, encompassing diagnostic innovations, treatment advancements, and individualized strategies. Ongoing research is pivotal for refining diagnostic and therapeutic paradigms in hypertension management.

Nanomedicine for the Treatment of Lungs Cancer Its Challenges and Future Perspective-A Review

A major public health concern with a global reach,lungs cancer necessitates cutting-edge techniques to treatment. Nanomedicine is a new technology that is currently being used to treat and diagnose lung cancer. This review examines the difficulties in using nano medicine to treat lung cancer and shows the promising directions for this rapidly developing field of study. The issues raised in this review cover a wide range of topics, such as medication delivery, targeted precision, toxicity, and legal obstacles. Approaches based on nanomedicine have the potential to get through these barriers thanks to improvements in drug delivery to lung cancer cell, a decrease in side effects, and increased therapeutic effectiveness. Additionally, this study explores the potential applications of nanomedicine for the treatment of lung cancer, highlighting the significance of cutting-edge technology including personalized medicine techniques,theranostic nanosystems, and targeted nanoparticles. These developments carry the possibility of individualized treatment plans, improved therapeutic results, and reduced side effects. Nanomedicine offers a multifaceted approach to address the challenges of lung cancer treatment, bringing new hope to patients and clinicians alike. By overcoming existing limitations and harnessing the potential of emerging technologies, nano medicine is poised to play a pivotal role in the future of lung cancer therapy. This review serves as a comprehensive overview of the field, shedding light on the path forward in the fight against lung cancer.

A PBPK model for PRRT with [177Lu]Lu-DOTA-TATE: Comparison of model implementations in SAAM II and MATLAB/SimBiology

Physiologically based pharmacokinetic (PBPK) models offer the ability to simulate and predict the biodistribution of radiopharmaceuticals and have the potential to enable individualised treatment planning in molecular radiotherapy. The objective of this study was to develop and implement a whole-body compartmental PBPK model for peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE in SimBiology to allow for more complex analyses. The correctness of the model implementation was ensured by comparing its outputs, such as the time-integrated activity (TIA), with those of a PBPK model implemented in SAAM II software. MethodsA combined PBPK model for [68Ga]Ga-DOTA-TATE and [177Lu]Lu-DOTA-TATE was developed and implemented in both SAAM II and SimBiology. A retrospective analysis of 12 patients with metastatic neuroendocrine tumours (NETs) was conducted. First, time-activity curves (TACs) and TIAs from the two software were calculated and compared for identical parameter values. Second, pharmacokinetic parameters were fitted to activity concentrations, analysed and compared. ResultsThe PBPK model implemented in SimBiology produced TIA results comparable to those generated by the model implemented in SAAM II, with a relative deviation of less than 0.5% when using the same input parameters. The relative deviation of the fitted TIAs was less than 5% when model parameter values were fitted to the measured activity concentrations. ConclusionThe proposed PBPK model implemented in SimBiology can be used for dosimetry in radioligand therapy and TIA prediction. Its outputs are similar to those generated by the PBPK model implemented in SAAM II, confirming the correctness of the model implementation in SimBiology.