Monitoring Treatment Response Research Articles

Determination of Tumor Marker Screening for Lung Cancer Using ROC Curves.

Lung cancer ranks first among malignant tumors worldwide and is a leading cause of cancer-related mortality in both men and women. Combining tumor marker testing is a strategy to screen individuals at high risk of pulmonary cancer and minimize pulmonary cancer mortality. Therefore, tumor marker screening is crucial. In this study, we analyzed combinations of tumor markers for lung cancer screening using receiver operating characteristic (ROC) curve analysis. A retrospective descriptive study was conducted on patients diagnosed with lung cancer, as well as healthy and benign lung diseases, using data from the China Huludao Central Hospital database between January 2016 and July 2022. The t-test and ROC curve were utilized to assess the effectiveness of individual tumor marker and the combination of multiple tumor markers. Tumor markers are molecular products metabolized and secreted by tumor tissues, characterized by cells or body fluids. They serve as indicators of tumor stage and grading, monitor treatment response, and predict recurrence. In this study, 267 healthy participants, 385 patients with benign lesions, and 296 patients with lung cancer underwent tumor marker screening. The sensitivity of five tumor markers-CEA, CYFRA21-1, NSE, pro-GRP, and CA125-was found to be <55%. This study revealed that a single tumor marker had limited value in lung cancer screening. However, combining two or more markers yielded varying area under the curves (AUC), with no significant impact on screening accuracy. The combination of CEA + CA125 demonstrated the highest accuracy for lung cancer screening in healthy participants. At a cutoff of 0.447 for CEA + CA125, the combination showed a sensitivity of 0.676 and specificity of 0.846 for lung cancer screening. Conversely, for patients with benign lung lesions, the optimal combination was CEA + NSE, with a cutoff of 0.393, yielding a sensitivity of 0.645 and specificity of 0.766 for lung cancer screening. The five tumor markers-CEA, CA125, CY211, NSE, GRP-show promising results in screening healthy individuals and patients with lung cancer. However, only CEA, NSE, and GRP effectively differentiate patients with benign lung lesions from those with lung cancer. A single tumor marker has limited utility in detecting and screening for lung cancer and should be combined with other tumor markers. CEA + CA125 emerges as a superior tumor marker for distinguishing healthy individuals from those with lung cancer, whereas the CEA + NSE combination is more effective in identifying tumor markers in patients with benign lung lesions and lung cancer.

Analytical validation of NeXT Personal®, an ultra-sensitive personalized circulating tumor DNA assay.

We describe the analytical validation of NeXT Personal®, an ultra-sensitive, tumor-informed circulating tumor DNA (ctDNA) assay for detecting residual disease, monitoring therapy response, and detecting recurrence in patients diagnosed with solid tumor cancers. NeXT Personal uses whole genome sequencing of tumor and matched normal samples combined with advanced analytics to accurately identify up to ~1,800 somatic variants specific to the patient's tumor. A personalized panel is created, targeting these variants and then used to sequence cell-free DNA extracted from patient plasma samples for ultra-sensitive detection of ctDNA. The NeXT Personal analytical validation is based on panels designed from tumor and matched normal samples from two cell lines, and from 123 patients across nine cancer types. Analytical measurements demonstrated a detection threshold of 1.67 parts per million (PPM) with a limit of detection at 95% (LOD95) of 3.45 PPM. NeXT Personal showed linearity over a range of 0.8 to 300,000 PPM (Pearson correlation coefficient = 0.9998). Precision varied from a coefficient of variation of 12.8% to 3.6% over a range of 25 to 25,000 PPM. The assay targets 99.9% specificity, with this validation study measuring 100% specificity and in silico methods giving us a confidence interval of 99.92 to 100%. In summary, this study demonstrates NeXT Personal as an ultra-sensitive, highly quantitative and robust ctDNA assay that can be used to detect residual disease, monitor treatment response, and detect recurrence in patients.

Circulating Tumor DNA (ctDNA) Clearance May Predict Treatment Response in Neoadjuvant Colorectal Cancer Management.

Background: Circulating tumor DNA (ctDNA) is extracellular DNA released by tumors and has been proposed as a marker of residual disease as well as a predictor of disease recurrence in the adjuvant setting. However, data are lacking on the utility of this biomarker in the neoadjuvant setting. Methods: We performed a retrospective study of stage III and IV colorectal cancer patients receiving neoadjuvant treatment at a single institution. Results: Seventeen patients converted from a positive pre-neoadjuvant ctDNA to a negative ctDNA prior to surgery. Five patients remained persistently positive despite systemic treatment. ctDNA conversion was found to be associated with a higher incidence of favorable treatment effect scores on final surgical pathology. There was no difference in recurrence-free survival in this small population. Furthermore, no added benefit was identified for patients receiving additional neoadjuvant therapy after the time of positive to negative ctDNA conversion. Conclusions: This study highlights the potential utility of ctDNA and the need for prospective trials in the neoadjuvant setting to monitor treatment response and guide decisions on treatment duration.

Development of New CD38 Targeted Peptides for Cancer Imaging

PurposeMultiple myeloma (MM) affects over 35,000 patients each year in the US. There remains a need for versatile Positron Emission Tomography (PET) tracers for the detection, accurate staging, and monitoring of treatment response of MM that have optimal specificity and translational attributes. CD38 is uniformly overexpressed in MM and thus represents an ideal target to develop CD38-targeted small molecule PET radiopharmaceuticals to address these challenges.ProceduresUsing phage display peptide libraries and pioneering algorithms, we identified novel CD38 specific peptides. Imaging bioconjugates were synthesized using solid phase peptide chemistry, and systematically analyzed in vitro and in vivo in relevant MM systems.ResultsThe CD38-targeted bioconjugates were radiolabeled with copper-64 (64Cu) with100% radiochemical purity and an average specific activity of 3.3 – 6.6 MBq/nmol. The analog NODAGA-PEG4-SL022-GGS (SL022: Thr-His-Tyr-Pro-Ile-Val-Ile) had a Kd of 7.55 ± 0.291 nM and was chosen as the lead candidate. 64Cu-NODAGA-PEG4-SL022-GGS demonstrated high binding affinity to CD38 expressing human myeloma MM.1S-CBR-GFP-WT cells, which was blocked by the non-radiolabeled version of the peptide analog and anti-CD38 clinical antibodies, daratumumab and isatuximab, by 58%, 73%, and 78%, respectively. The CD38 positive MM.1S-CBR-GFP-WT cells had > 68% enhanced cellular binding when compared to MM.1S-CBR-GFP-KO cells devoid of CD38. Furthermore, our new CD38-targeted radiopharmaceutical allowed visualization of tumors located in marrow rich bones, remaining there for up to 4 h. Clearance from non-target organs occurred within 60 min. Quantitative PET data from a murine disseminated tumor model showed significantly higher accumulation in the bones of tumor-bearing animals compared to tumor-naïve animals (SUVmax 2.06 ± 0.4 versus 1.24 ± 0.4, P = 0.02). Independently, tumor uptake of the target compound was significantly higher (P = 0.003) compared to the scrambled peptide, 64Cu-NODAGA-PEG4-SL041-GGS (SL041: Thr-Tyr-His-Ile-Pro-Ile-Val). The subcutaneous MM model demonstrated significantly higher accumulation in tumors compared to muscle at 1 and 4 h after tracer administration (SUVmax 0.8 ± 0.2 and 0.14 ± 0.04, P = 0.04 at 1 h; SUVmax 0.89 ± 0.01 and 0.09 ± 0.01, P = 0.0002 at 4 h).ConclusionsThe novel CD38-targeted, radiolabeled bioconjugates were specific and allowed visualization of MM, providing a starting point for the clinical translation of such tracers for the detection of MM.

CtDNA predicts clinical T1a to pathological T3a upstaging after partial nephrectomy.

Most patients diagnosed with clear cell renal cell carcinoma (ccRCC) are also detected with small and organ-confined tumors, and the majority of these are classified as clinical tumor stage 1a (cT1a). A considerable proportion of patients with cT1 RCC shows tumor upstaging to pathological stage 3a (pT3a), and these patients have worse oncological outcomes. The role of circulating tumor DNA (ctDNA) in RCC has been limited to monitoring treatment response and resistance. Therefore, the present study aimed to evaluate the potential of ctDNA in predicting pT3a upstaging in cT1a ccRCC. We sequenced plasma samples preoperatively collected from 48 patients who had undergone partial nephrectomy for cT1a ccRCC using data from a prospective cohort RCC. The ctDNA were profiled and compared with clinicopathological ccRCC features to predict pT3a upstaging. Associations between ctDNA, tumor complexity, and pT3a upstaging were evaluated. Tumor complexity was assessed using the anatomical classification system. Univariate analysis used chi-squared and Student's t-tests; multivariate analysis considered significant factors from univariate analyses. Of the 48 patients with cT1a ccRCC, 12 (25%) were upstaged to pT3a, with ctDNA detected in 10 (20.8%), predominantly in patients with renal sinus fat invasion (SFI; n = 8). Among the pT3a group, ctDNA was detected in 75%, contrasting with only 2.8% in patients with pT1a (1/36). Detection of ctDNA was the only significant preoperative predictor of pT3a upstaging, especially in SFI. This study is the first to suggest ctDNA as a preoperative predictor of pT3a RCC upstaging from cT1a based on preoperative radiological images.

Pathological Mechanisms and Novel Testing Methods in Thrombotic Thrombocytopenic Purpura.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon, but potentially disabling or even deadly, thrombotic microangiopathy with a well-studied mechanism of ADAMTS13 deficiency or dysfunction. While established treatments are largely effective, the standard ADAMTS13 testing required to definitively diagnose TTP may cause delays in diagnosis and treatment, highlighting the need for rapid and effective diagnostic methods. Additionally, the heterogeneous presentation and varied inciting events of TTP suggest more variation in its mechanism than previously thought, implying three potential pathways rather than the accepted two. The recent discovery of ADAMTS13 conformation as a potential contributor to TTP in addition to the proposal of using the absolute immature platelet count (A-IPC) as a biomarker, present novel areas for monitoring and treatment. A-IPC in particular may serve as a more rapid and accurate diagnostic test to distinguish TTP from non-TTP TMAs and to monitor treatment response and relapse. These considerations highlight the need to further study TTP in order to improve best practices and patient care.

Association between Ustekinumab Trough Levels, Serum IL-22, and Oncostatin M Levels and Clinical and Biochemical Outcomes in Patients with Crohn's Disease.

Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients with Crohn's disease. Monitoring treatment response can improve disease management and reduce healthcare costs. We investigated whether UST trough levels (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of non-response by analysing their correlation with clinical and biochemical outcomes in CD. Methods: Patients with CD initiating UST treatment from October 2018 to September 2020 were enrolled at six Italian centres for inflammatory bowel disease (IBD). Clinical and biochemical data were collected at four time points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. TLs were measured during maintenance, at the second SC dose, and at the fourth SC dose. IL-22 and OSM serum levels were assessed at baseline and the second SC dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated with clinical response, clinical remission, biochemical remission, and endoscopic remission using the appropriate statistical tests. Results: Out of eighty-four initially enrolled patients, five were lost to follow-up, and eleven discontinued the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical remission based on faecal calprotectin levels, and 61.8% achieved clinical remission. TLs at the second SC dose significantly correlated with biochemical remission at the same time point (p = 0.011). However, TLs did not correlate with clinical remission. Baseline OSM levels did not correlate with biochemical or clinical remission or response. IL22 levels notably decreased during UST therapy (p = 0.000), but its values did not correlate with biochemical or clinical remission. Conclusions: UST is an effective therapy for patients with CD. TLs measured at the second SC dose significantly correlated with biochemical remission, emphasising their potential role in treatment monitoring. Levels of OSM and IL-22, despite a significant decrease in the latter during therapy, did not exhibit correlations with clinical or biochemical outcomes in our study. Further studies are needed to confirm these findings.

Plasmonic array assisted mass spectrometry for preferential metabolite detection

Metabolites, depicting physiological and pathophysiological state, underpin diverse disease-associated phenomena. Metabolite detection offers insights for identifying disease biomarkers and monitoring treatment responses, thereby facilitating early disease diagnosis and personalized medicine. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) holds promise in molecular profiling, with advanced materials emerging as efficient matrices for metabolite detection. Yet, their preferences in analyzing various metabolites have not been systematically explored, hindering the development of matrices for suitable clinical practice. Herein, we report plasmonic array assisted MS for fast and direct quantification of specific metabolites in human biofluids. Plasmonic array is prepared by self-assembling hybrid bimetallic alloys at liquid–liquid interfaces. Large scale screening of 37 metabolites exhibited LDI preferences of plasmonic array especially for nucleosides. Plasmonic array enables sensitive and selective detection of nucleosides, due to the synergistic effect via alloy composition and chemical interactions without the use of costly antibodies. Consequently, accurate quantification is achieved with a recovery rate of 103.18 % ± 3.78 % for inosine, consuming a trace amount of serum as low as 4 μL within seconds. This work provides useful guidelines for matrix design in the MALDI MS analysis of metabolites toward biomedical applications.

Accuracy of the tuberculosis molecular bacterial load assay to diagnose and monitor response to anti-tuberculosis therapy: a longitudinal comparative study with standard-of-care smear microscopy, Xpert MTB/RIF Ultra, and culture in Uganda

In 2018, the tuberculosis molecular bacterial load assay (TB-MBLA), a ribosomal RNA-based test, was acknowledged by WHO as a molecular assay that could replace smear microscopy and culture for monitoring tuberculosis treatment response. In this study, we evaluated the accuracy of TB-MBLA for diagnosis and monitoring of treatment response in comparison with standard-of-care tests. For this longitudinal prospective study, patients aged 18 years or older with presumptive tuberculosis (coughing for at least 2 weeks, night sweats, and weight loss) were enrolled at China-Uganda Friendship Hospital Naguru (Kampala, Uganda). Participants were evaluated for tuberculosis by TB-MBLA in comparison with Xpert MTB/RIF Ultra (Xpert-Ultra) and smear microscopy, with Mycobacteria Growth Indicator Tube (MGIT) culture as a reference test. Participants who were positive on Xpert-Ultra were enrolled on a standard 6-month anti-tuberculosis regimen, and monitored for treatment response at weeks 2, 8, 17, and 26 after initiation of treatment and then 3 months after treatment. Between Nov 15, 2019, and June 15, 2022, 210 participants (median age 35 years [IQR 27-44]) were enrolled. 135 (64%) participants were male and 72 (34%) were HIV positive. The pretreatment diagnostic sensitivities of TB-MBLA and Xpert-Ultra were similar (both 99% [95% CI 95-100]) but the specificity was higher for TB-MBLA (90%[83-96]) than for Xpert-Ultra (78% [68-86]). Ten participants were Xpert-Ultra trace positive, eight (80%) of whom were negative by TB-MBLA and MGIT culture. Smear microscopy had lower diagnostic sensitivity (75%[65-83]) but higher specificity (98% [93-100]) than TB-MBLA and Xpert-Ultra. Among participants who were smear microscopy negative, the sensitivity of TB-MBLA was 96% (95 CI 80-100) and was 100% (95% CI 86-100) in those who were HIV positive. 129 (61%) participants were identified as tuberculosis positive by Xpert-Ultra and these individuals were enrolled in the treatment group and monitored for treatment response. According to TB-MBLA, 19 of these patients cleared bacillary load to zero by week 2 of treatment and remained negative throughout the 6-month treatment follow-up. Positivity for tuberculosis decreased with treatment as measured by all tests, but therate was slower with Xpert-Ultra. Consequently, 31 (33%) of 95 participants were still Xpert-Ultra positive at the end of treatment but were clinically well and negative on TB-MBLA and culture at 6 months of treatment. Two patients were still Xpert-Ultra positive with a further 3 months of post-treatment follow-up. The rate of conversion to negative of the DNA-based Xpert-Ultra was 3·3-times slower than that of the rRNA-based TB-MBLA. Consequently for the same patient, it would take 13 weeks and 52 weeks to reach complete tuberculosis negativity by TB-MBLA and Xpert-Ultra, respectively. Participants who were positive on smear microscopy at 8weeks, who received an extra month of intensive treatment, had a similar TB-MBLA-measured bacillary load at 8weeks to those who were smear microscopy negative. TB-MBLA has a similar performance to Xpert-Ultra for pretreatment diagnosis of tuberculosis, but is more accurate at detecting and characterising the response to treatment than Xpert-Ultra and standard-of-care smear microscopy. European and Developing Countries Clinical Trials Partnership, Makerere University Research and Innovation Fund, US National Institutes of Health.

Longitudinal metabolite profiling of Streptococcus pneumoniae-associated community-acquired pneumonia

IntroductionLongitudinal biomarkers in patients with community-acquired pneumonia (CAP) may help in monitoring of disease progression and treatment response. The metabolic host response could be a potential source of such biomarkers since it closely associates with the current health status of the patient.ObjectivesIn this study we performed longitudinal metabolite profiling in patients with CAP for a comprehensive range of metabolites to identify potential host response biomarkers.MethodsPreviously collected serum samples from CAP patients with confirmed Streptococcus pneumoniae infection (n = 25) were used. Samples were collected at multiple time points, up to 30 days after admission. A wide range of metabolites was measured, including amines, acylcarnitines, organic acids, and lipids. The associations between metabolites and C-reactive protein (CRP), procalcitonin, CURB disease severity score at admission, and total length of stay were evaluated.ResultsDistinct longitudinal profiles of metabolite profiles were identified, including cholesteryl esters, diacyl-phosphatidylethanolamine, diacylglycerols, lysophosphatidylcholines, sphingomyelin, and triglycerides. Positive correlations were found between CRP and phosphatidylcholine (34:1) (cor = 0.63) and negative correlations were found for CRP and nine lysophosphocholines (cor = − 0.57 to − 0.74). The CURB disease severity score was negatively associated with six metabolites, including acylcarnitines (tau = − 0.64 to − 0.58). Negative correlations were found between the length of stay and six triglycerides (TGs), especially TGs (60:3) and (58:2) (cor = − 0.63 and − 0.61).ConclusionThe identified metabolites may provide insight into biological mechanisms underlying disease severity and may be of interest for exploration as potential treatment response monitoring biomarker.

Concomitant thyroiditis and orchitis induced by immune checkpoint inhibitors detected on [18F]FDG PET/CT

BackgroundThe clinical management of malignant melanoma (MM) has undergone a significant revolution with the implementation of immune checkpoint inhibitors (ICIs). While these therapeutic agents stimulate the host immune system against cancer, they may also lead to immune-related adverse events (IrAEs). Positron emission computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) has proven successful in detecting IrAEs in cancer patients undergoing ICI. In our case, we report a rare occurrence of ICIs-induced concomitant thyroiditis and orchitis detected on [18F]FDG PET/CT.Case presentationWe present a case involving a 61-year-old man referred to our hospital due to MM. Following surgical excision and sentinel lymph node mapping, he underwent an initial [18F]FDG PET/CT, which yielded negative results. However, a follow-up PET/CT after 9 months revealed metastases in the lungs and lymph nodes. Subsequently, he initiated an ICI-based therapeutic regimen. After 3 months, he reported progressively worsening fatigue and the onset of testicular pain. A testicular ultrasound showed heterogeneous echotexture in both testicles with mildly increased vascularity. A subsequent PET/CT demonstrated complete regression of previously described pathological lesions in the lungs and metastatic lymph nodes. However, diffusely increased tracer uptake was observed in both the thyroid gland and testicles, findings absent in the pre-ICI examination. These were interpreted as IrAEs and promptly treated with corticosteroids, resulting in complete resolution of symptoms.Conclusions[18F]FDG PET/CT plays a crucial role in staging and monitoring treatment response in cancer patients. When assessing subjects undergoing ICI-based therapies, particular emphasis should be given to detecting unusual IrAEs, as exemplified in our case.

The chest X-ray score baseline in predicting continuous oxygen therapy failure in low-risk aged patients after thoracic surgery.

Radiographic severity assessment can be instrumental in diagnosing postoperative pulmonary complications (PPCs) and guiding oxygen therapy. The radiographic assessment of lung edema (RALE) and Brixia scores correlate with disease severity, but research on low-risk elderly patients is lacking. This study aimed to assess the efficacy of two chest X-ray scores in predicting continuous oxygen therapy (COT) treatment failure in patients over 70 years of age after thoracic surgery. From January 2019 to December 2021, we searched for patients aged 70 years and above who underwent thoracic surgery and received COT treatment, with a focus on those at low risk of respiratory complications. Bedside chest X-rays, RALE, Brixia scores, and patient data were collected. Univariate, multivariate analyses, and 1:2 matching identified risk factors. Receiver operating characteristic (ROC) curves determined score sensitivity, specificity, and predictive values. Among the 242 patients surviving to discharge, 19 (7.9%) patients experienced COT failure. COT failure correlated with esophageal cancer surgeries, thoracotomies (36.8% vs. 9%, P=0.003; 26.3% vs. 9.4%, P=0.004), and longer operation time (3.4 vs. 2.8 h, P=0.003). Surgical approach and RALE score were independent risk factors. The prediction model had an area under the curve (AUC) of 0.839 [95% confidence interval (CI), 0.740-0.938]. Brixia and RALE scores predicted COT failure with AUCs of 0.764 (95% CI, 0.650-0.878) with a cut-off value of 6.027 and 0.710 (95% CI, 0.588-0.832) with a cut-off value of 17.134, respectively, after 1:2 matching. The RALE score predict the risk of COT failure in elderly, low-risk thoracic patients better than the Brixia score. This simple, cheap, and noninvasive method helps evaluate postoperative lung damage, monitor treatment response, and provide early warning for oxygen therapy escalation. Further studies are required to confirm the validity and applicability of this model in different settings and populations.

Lost in space(s): Multimodal neuroimaging of disorientation along the Alzheimer's disease continuum.

Orientation is a fundamental cognitive faculty and the bedrock of the neurologic examination. Orientation is defined as the alignment between an individual's internal representation and the external world in the spatial, temporal, and social domains. While spatial disorientation is a recognized hallmark of Alzheimer's disease (AD), little is known about disorientation beyond space in AD. This study aimed to explore disorientation in spatial, temporal, and social domains along the AD continuum. Fifty-one participants along the AD continuum performed an ecological orientation task in the spatial, temporal, and social domains while undergoing functional MRI. Disorientation in AD followed a three-way association between orientation domain, brain region, and disease stage. Specifically, patients with early amnestic mild cognitive impairment exhibited spatio-temporal disorientation and reduced brain activity in temporoparietal regions, while patients with AD dementia showed additional social disorientation and reduced brain activity in frontoparietal regions. Furthermore, patterns of hypoactivation overlapped different subnetworks of the default mode network, patterns of fluorodeoxyglucose hypometabolism, and cortical atrophy characteristic of AD. Our results suggest that AD may encompass a disorder of orientation, characterized by a biphasic process manifesting as early spatio-temporal and late social disorientation. As such, disorientation may offer a unique window into the clinicopathological progression of AD. SIGNIFICANCE STATEMENT: Despite extensive research into Alzheimer's disease (AD), its core cognitive deficit remains a matter of debate. In this study, we investigated whether orientation, defined as the ability to align internal representations with the external world in spatial, temporal, and social domains, constitutes a core cognitive deficit in AD. To do so, we used PET-fMRI imaging to collect behavioral, functional, and metabolic data from 51 participants along the AD continuum. Our findings suggest that AD may constitute a disorder of orientation, characterized by an early spatio-temporal disorientation and followed by late social disorientation, manifesting in task-evoked and neurodegenerative changes. We propose that a profile of disorientation across multiple domains offers a unique window into the progression of AD and as such could greatly benefit disease diagnosis, monitoring, and evaluation of treatment response.

Tracing the disc: The novel qualitative morphometric MRI based disc degeneration classification system.

This study aimed to develop a classification system for lumbar disc degeneration using routine magnetic resonance images (MRIs) that is easily applicable and unaffected by existing classifications' limitations, and to compare its reliability, reproducibility, and discriminative power to the widely used Pfirrmann classification. Five features were graded. This new classification system has eight grades, with at least one of these five features altering each grade. The T2-weighted sagittal images were acquired using a rapid spin-echo sequence with a repetition time of 2680 to 4900 milliseconds, an echo time of 100 to 109 milliseconds, and an echo train length of 17. Slice thick was 4 mm and the display field of view was 32 × 32 cm. The new classification system used five features: signal intensity, disc height, disc boundary regularity, and nucleus annulus separation. Increased signal intensity, decreased height, decreased regularity, and decreased nucleus-annulus separation indicated degeneration. Four raters classified 400 discs from 80 patients using the Pfirrmann and Novel systems. Statistical analyses were conducted to investigate reliability and correlation. The overall ICC and kappa values were found to be higher in the novel classification. (0.988 indicating excellent agreement for ICC and 0.76/0.94 indicating good-very good agreement for kappa). The Kendall tau c value, which shows the correlation between the two classifications and indicates the validity of the new classification, was 0.872, which is very strong. Through the use of cross-tabulations, the discriminatory power of the two newly added classification criteria was determined. This study demonstrates the intra-rater and inter-rater reliability of an easy-to-use, discriminative novel morphometric MRI based classification system for lumbar disc degeneration. The differentiation of grades based on five distinct criteria may generate novel hypotheses regarding treatment selection and response monitoring, as well as new insights into the study of disc degeneration.

Reviewing the progress of cancer research in the USA

This review provides a comprehensive analysis of the progress made in cancer research within the United States. Over the past few decades, significant strides have been taken to understand the complexities of cancer, leading to breakthroughs in diagnostics, treatment modalities, and overall patient care. The review explores key themes, including advancements in genomic medicine, immunotherapy, and personalized treatment approaches. Advancements in genomic medicine have emerged as a cornerstone of cancer research, allowing for a deeper understanding of the genetic basis of various cancers. The integration of precision medicine techniques has facilitated the identification of specific genetic mutations, paving the way for targeted therapies tailored to individual patients. Genomic profiling has not only enhanced diagnostic accuracy but has also provided valuable insights into cancer heterogeneity, guiding researchers toward more effective and personalized treatment strategies. Immunotherapy has revolutionized cancer treatment by harnessing the body's immune system to target and eliminate cancer cells. The review delves into the remarkable progress in developing immune checkpoint inhibitors, adoptive cell therapies, and cancer vaccines. These innovations have shown unprecedented success in treating previously challenging malignancies, offering new hope for patients with advanced-stage cancers. The concept of personalized medicine is further explored, emphasizing the shift from a one-size-fits-all approach to tailoring treatments based on individual patient characteristics. The advent of liquid biopsies and advanced imaging techniques has enabled real-time monitoring of treatment responses, facilitating timely adjustments and improving overall patient outcomes. Despite these advancements, the review acknowledges persistent challenges, such as the need for enhanced collaboration between research institutions, the imperative for increased funding, and the importance of addressing healthcare disparities in cancer outcomes. The ongoing commitment to interdisciplinary research, translational initiatives, and a patient-centered approach is emphasized as essential for overcoming these challenges and further propelling the field of cancer research in the USA. In conclusion, this review paints a comprehensive picture of the remarkable progress in cancer research within the United States. The integration of genomic insights, immunotherapeutic breakthroughs, and personalized treatment approaches underscores a promising future for cancer patients, while acknowledging the necessity of continued efforts to address existing challenges and propel the field toward even greater advancements.

Digital twins in dosimetry and radiotherapy, a survey and some applications

Digital Twins (DTs) are emerging as a powerful tool in several applications, including Dosimetry and Radiotherapy (RT). Indeed, DTs have increased their effectiveness, up to the point that can be considered as virtual replicas of physical objects, processes, or systems. Through predictive modeling, DTs can determine optimal doses in radiation therapy, assist in defining personalized treatment schedules for individual patients, and monitor treatment responses. Moreover, DTs play a pivotal role in designing radioisotope production processes in the field of nuclear medicine. This can help to ensure the most effective treatment possible while minimizing the risk of side effects.As a frontier case example, DTs can be employed in the analysis of a possible new source for flash radiotherapy worth with respect to their effectiveness parameters like Radio-Biological Effectiveness (RBE) or cell Surviving Fraction (SF). Flash techniques involve the delivery of a high dose of radiation in a short time, reducing damage to surrounding healthy tissue while possibly increasing damage to malignant cells. DTs could be used to simulate and collect data about particle interactions with the treated tissues, optimizing the treatment and leading to improved outcomes.The most powerful tools that can be applied in DTs development are the Monte Carlo (MC) codes, particularly those with the highest capability of a detailed material/geometry description through an automatized spatial discretization approach like the one based on Unstructured Mesh (UM), allowing a common mathematical domain for both particle/radiation transport and thermal, fluid-dynamics and mechanical simulations. What comes out from various kind of applications is a common ground in terms of data management, phase space identification, simulation tools, that can be easily recognized even if spanning from cell response to technological devices, making realistic the perspective of the setup of general optimization procedures.

Insights into the diagnosis and management of sarcoid uveitis: A review.

Sarcoidosis is a leading cause of non-infectious uveitis that commonly affects middle-aged individuals and has a female preponderance. The disease demonstrates age, sex and ethnic differences in clinical manifestations. A diagnosis of sarcoidosis is made based on a compatible clinical presentation, supporting investigations and histologic evidence of non-caseating granulomas, although biopsy is not always possible. Multimodal imaging with widefield fundus photography, optical coherence tomography and angiography can help in the diagnosis of sarcoid uveitis and in the monitoring of treatment response. Corticosteroid remains the mainstay of treatment; chronic inflammation requires steroid-sparing immunosuppression. Features on multimodal imaging such as vascular leakage may provide prognostic indicators of outcome. Female gender, prolonged and severe uveitis, and posterior involving uveitis are associated with poorer visual outcomes.

Semiquantitative 18F-FDG PET/CT in monitoring glucocorticoid response of immunoglobulin G4-related effusive constrictive pericarditis: a case report

BackgroundImmunoglobulin G4 (IgG4)-related effusive constrictive pericarditis (ECP) is a rare manifestation of IgG4-related disease (IgG4-RD). It can lead to persistent pericardial fibrosis, resulting in cardiac tamponade, diastolic dysfunction, and heart failure. Glucocorticoids are the primary treatment for effectively reducing inflammation and preventing fibrosis. However, guidelines for monitoring treatment response are lacking and tapering glucocorticoid therapy for specific target organs remains a challenge. Recent studies on IgG4-RD have demonstrated that semiquantitative measurements of fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the main involved organs in positron emission tomography/computed tomography (PET/CT) scanning are correlated to disease activity. We present a case of IgG4-related ECP to demonstrate the usefulness of 18F-FDG PET/CT for diagnosing and treatment follow-up of IgG4-related ECP.Case presentationHerein, a 66-year-old woman diagnosed with IgG4-related ECP presented with breathlessness, leg swelling, rales, and fever. Laboratory tests revealed markedly elevated levels of C-reactive protein, and transthoracic echocardiography revealed constrictive physiology with effusion. High IgG4 levels suggested an immune-related pathogenesis, while viral and malignant causes were excluded. Subsequent pericardial biopsy revealed lymphocyte and plasma cell infiltration in the pericardium, confirming the diagnosis of IgG4-related ECP. 18F-FDG PET/CT revealed increased uptake of 18F-FDG in the pericardium, indicating isolated cardiac involvement of IgG4-RD. Treatment with prednisolone and colchicine led to a rapid improvement in the patient’s condition within a few weeks. Follow-up imaging with 18F-FDG PET/CT after 3 months revealed reduced inflammation and improved constrictive physiology on echocardiography, leading to successful tapering of the prednisolone dose and discontinuation of colchicine.ConclusionThe rarity of IgG4-related ECP and possibility of multiorgan involvement in IgG4-RD necessitates a comprehensive diagnostic approach and personalized management. This case report highlights the usefulness of 18F-FDG PET/CT in the diagnosis and treatment follow-up of isolated pericardial involvement in IgG4-RD.

Considering Context-Specific microRNAs in Ischemic Stroke with Three "W": Where, When, and What.

MicroRNAs are short non-coding RNA molecules that function as critical regulators of various biological processes through negative regulation of gene expression post-transcriptionally. Recent studies have indicated that microRNAs are potential biomarkers for ischemic stroke. In this review, we first illustrate the pathogenesis of ischemic stroke and demonstrate the biogenesis and transportation of microRNAs from cells. We then discuss several promising microRNA biomarkers in ischemic stroke in a context-specific manner from three dimensions: biofluids selection for microRNA extraction (Where), the timing of sample collection after ischemic stroke onset (When), and the clinical application of the differential-expressed microRNAs during stroke pathophysiology (What). We show that microRNAs have the utilities in ischemic stroke diagnosis, risk stratification, subtype classification, prognosis prediction, and treatment response monitoring. However, there are also obstacles in microRNA biomarker research, and this review will discuss the possible ways to improve microRNA biomarkers. Overall, microRNAs have the potential to assist clinical treatment, and developing microRNA panels for clinical application is worthwhile.

Bone Trabecular Pattern Analysis in Odontogenic Cysts Using Cone Beam Computed Tomography: A Clinical Retrospective Study.

Introduction The cysts of the maxillofacial region account for one of the most common pathologies of the head and neck region after the mucosal pathologies. Radiography provides an essential clue in early diagnosis and triaging, but it continues further as it is used to evaluate the post-treatment outcome. However, manual analysis is prone to errors. In this scenario, fractal analysis (FA) in radiographs uses mathematical methods to analyse the changes in grey scales in a given radiographic image. FA in odontogenic cysts is used to characterise their complexity, uncover hidden patterns, monitor treatment response, and potentially provide prognostic information. This paper aimed to assess the fractal characteristics of the radicular cyst (RC), dentigerous cyst (DC), and odontogenic keratocyst (OKC) using cone beam computed tomography (CBCT). The objective was to calculate fractal dimension (FD) values expressed in each of these cysts, which could prove to be a radiological adjunct in diagnosing the above cysts. Materials and methods As this is a retrospective study, the archives of CBCT images from June 2021 to December 2023 were obtained from patients diagnosed and confirmed with a histopathological diagnosis with RC, DC, and OKC. The FA was performed using Image J Software(Ver 1.51, National Institute ofHealth Bethesda, Fiji). The cortical and cancellous bones were segmented using thresholding techniques and converted to binary images. The mean FD of the three planes was then compared to establish the distinctive fractal characteristic for the specific odontogenic cysts. A one-way ANOVA was performed using the Statistical Product and Service Solutions (SPSS) (version 23.0; IBM SPSS Statistics for Windows, Armonk, NY) to determine the difference between FD values of RC, DC, and OKC with a significance level less than 0.05. Results The FD values of DC, RC, and OKC were 1.33 ± 0.17, 1.08 ± 0.16, and 1.65 ± 0.12, respectively. The results indicated that OKC had higher FD values than DC and RC, which means that OKC had lesser bone destruction compared to DC and RC. Inferential statistics showed that the one-way ANOVA was used to compare the means of the three groups of FD data. When calculated for the three groups, the F-statistic value was at 7.29, which yielded a P value of 0.03, making it statistically significant for a 95% confidence interval (p<0.05). Conclusion Our CBCT study on bone trabecular pattern analysis using FD and FAin odontogenic cysts reveals distinct alterations in bone parameters among different cyst types. The probability of higher FD values in OKC is because of lesser cortical bone destruction in OKC compared to the other cyst types. These findings have potential implications for diagnosing, treating, and prognosticating odontogenic cysts.