Assessment Of Treatment Response Research Articles

Does serum neurofilament light chain measurement influence therapeutic decisions in multiple sclerosis?

BackgroundThe assessment of serum neurofilament light chain (sNfL) concentration in multiple sclerosis (MS) is a useful tool for predicting clinical outcomes and assessing treatment response. However, its use in clinical practice is still limited. We aimed to assess how measurement of sNfL influences neurologists’ treatment decisions in MS. MethodsWe conducted a cross-sectional, web-based study in collaboration with the Spanish Society of Neurology. Neurologists involved in MS care were presented with different simulated case scenarios of patients experiencing either their first demyelinating MS event or a relapsing-remitting MS. The primary outcome was therapeutic inertia (TI), defined as the absence of treatment initiation or intensification despite elevated sNfL levels. Nine cases were included to estimate the TI score (range 0–9, where higher values represented a higher degree of TI). ResultsA total of 116 participants were studied. Mean age (standard deviation-SD) was 41.9 (10.1) years, 53.4 % male. Seventy-eight (67.2 %) were neurologists fully dedicated to the care of demyelinating disorders. Mean (SD) TI score was 3.65 (1.01). Overall, 92.2 % of participants (n = 107) presented TI in at least 2/9 case scenarios. The lack of full dedication to MS care (p = 0.014), preference for taking risks (p = 0.008), and low willingness to adopt evidence-based innovations (p = 0.009) were associated with higher TI scores in the multivariate analysis after adjustment for confounders. ConclusionTI was a common phenomenon among neurologists managing MS patients when faced with the decision to initiate or escalate treatment based on elevated sNfL levels. Identifying factors associated with this phenomenon may help optimize treatment decisions in MS care.

Identifying biomarkers for nasopharyngeal carcinoma diagnosis and chemoradiotherapy response using serum endogenous small molecules profiling

Changes in metabolic characteristics are important features of tumor progression and prognosis, including nasopharyngeal carcinoma (NPC). Identifying serum metabolites as potential diagnostic and chemoradiotherapy response biomarkers for NPC is therefore crucial. In this study, ultra-performance liquid chromatography coupled with linear ion trap quadrupole orbitrap high-resolution mass spectrometry (UPLC-LTQ-Orbitrap MS) was used to analyze metabolic variations among controls, NPC patients, and NPC patients undergoing chemoradiotherapy (CRT). Univariate and multivariate analyses revealed seven differential metabolites between the control and NPC groups and eleven metabolites between the CRT and NPC groups. Five common metabolites, gluconic acid, palmitic acid, LysoPC (15:0/0:0), stearic acid, and LysoPC (20:2(11Z,14Z)/0:0), were consistently altered across groups. Notably, the first four metabolites were adjusted closer to normal after chemoradiotherapy, while this change is not reflected at LysoPC (20:2(11Z,14Z)/0:0). These common metabolites were enriched in five pathways. These findings underscore the importance of serum metabolite profiling in NPC diagnosis and treatment response assessment and offer a promising foundation for further clinical research.

Role of serial fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) in assessing treatment response in treatment naïve chronic pulmonary aspergillosis subjects.

The role of 2-deoxy-2-18(F) fluoro-D-glucose (FDG) positron emission tomography (PET)-computed tomography (CT) in assessing treatment response in chronic pulmonary aspergillosis (CPA) remains to be determined. To compare changes in FDG-PET/CT parameters in CPA subjects with treatment success or failure. We treated consecutive treatment-naïve CPA subjects with six months of oral itraconazole. We performed PET-CT at baseline and six months. A multi-disciplinary team categorized response as treatment success or failure. We recorded the maximum standardised uptake value (SUVmax), SUVpeak, and total glycolytic activity (TLG). After treatment, FDG uptake similar to the background uptake or ≥13 units decline in Z-score was considered a complete metabolic response (CMR). A >25%, >30%, and > 45% decline in SUVmax, SUVpeak, and TLG was labelled as a partial metabolic response (PMR). A >30%, >30%, or >75% increase in the SUVmax, SUVpeak, and TLG represented progressive metabolic disease. We included 94 CPA subjects (63 males) with a mean age of 46.2 years. A follow-up PET-CT was performed on 77 subjects. We recorded treatment success and failure in 43 and 34 subjects. The median SUVmax at baseline was 6.7, which significantly reduced with treatment. CMR was seen in 18.6% of those with treatment success and none with treatment failure. A higher proportion of subjects with treatment success achieved PMR. 19% of the subjects with treatment success had progressive metabolic disease. FGD-PET/CT demonstrated metabolic activity in all CPA subjects. Most PET-CT parameters improved with treatment; however, one-fifth of the subjects were misclassified on PET-CT.

Radiomic-Based Prediction of Lesion-Specific Systemic Treatment Response in Metastatic Disease.

Despite sharing the same histologic classification, individual tumors in multi metastatic patients may present with different characteristics and varying sensitivities to anticancer therapies. In this study, we investigate the utility of radiomic biomarkers for prediction of lesion-specific treatment resistance in multi metastatic leiomyosarcoma patients. Using a dataset of n=202 lung metastases (LM) from n=80 patients with 1648 pre-treatment computed tomography (CT) radiomics features and LM progression determined from follow-up CT, we developed a radiomic model to predict the progression of each lesion. Repeat experiments assessed the relative predictive performance across LM volume groups. Lesion-specific radiomic models indicate up to a 4.5-fold increase in predictive capacity compared with a no-skill classifier, with an area under the precision-recall curve of 0.70 for the most precise model (FDR = 0.05). Precision varied by administered drug and LM volume. The effect of LM volume was controlled by removing radiomic features at a volume-correlation coefficient threshold of 0.20. Predicting lesion-specific responses using radiomic features represents a novel strategy by which to assess treatment response that acknowledges biological diversity within metastatic subclones, which could facilitate management strategies involving selective ablation of resistant clones in the setting of systemic therapy.

Early circulating tumor DNA (ctDNA) changes during treatment with immune checkpoint inhibitors (ICI) as a predictor of clinical outcomes in patients (pts) with advanced stage melanoma/skin cancer.

225 Background: ctDNA monitoring has shown promising results in predicting relapse in resected solid tumors. Its role in treatment response assessment and predicting survival outcomes in the unresectable or metastatic disease setting merits further investigation. In our study, we attempt to assess the role of early ctDNA changes in predicting disease response, progression, and overall survival outcomes in pts with advanced stage melanoma/skin cancer treated with ICI therapy. Methods: A retrospective analysis using a personalized, tumor-informed ctDNA assay (Natera) on prospectively collected plasma samples from pts with unresectable stage III/IV melanoma/skin cancer treated with anti-PD-1 based therapy at the University of Wisconsin (Madison) was performed. Baseline ctDNA levels were assessed prior to the start of treatment and at 3-4 weeks (i.e. prior to the second treatment dose). A logistic regression model was used to evaluate the odds of overall disease control [complete response + partial response + stable disease, per RECIST version 1.1] based on the change in ctDNA levels (decrease vs increase) between both time points. Cox proportional hazard models were used to investigate the effects of ctDNA level change on progression free survival (PFS) and overall survival (OS). Results: 46 pts were evaluated. 82% melanoma, 14% Merkel cell carcinoma, 2% skin adenocarcinoma and 2% squamous cell carcinoma. 77% were treated with dual ICI (anti-PD-1 based) therapy and 23% with anti-PD-1 monotherapy. Median follow up was 12.1 months. Median change in ctDNA levels from baseline were -4.83 MTM/mL among pts with ctDNA decrease and +37.39 MTM/mL among pts with ctDNA increase. A qualitative decrease in ctDNA level was associated with overall disease control (OR 65.00, 95% CI 11.88-587.89, p<0.0001), longer PFS (HR 0.08, 95% CI 0.03-0.22, p<0.0001), and longer OS (HR 0.17, 95% CI 0.05-0.54, p=0.0008) compared to an increase in ctDNA level from baseline to 3-4 weeks after starting ICI therapy. Median PFS was not reached (NR) and 1.63 months; and median OS was NR and 5.57 months among pts with ctDNA decrease and ctDNA increase, respectively. Conclusions: We found that early ctDNA dynamics after 3-4 weeks of ICI initiation in pts with advanced melanoma/skin cancer appears to be a candidate strategy to predict treatment response, risk of progression, and potentially long-term survival. Larger prospective studies are warranted to validate the utility of ctDNA in treatment monitoring.

The impact of introducing deep learning based [18F]FDG PET denoising on EORTC and PERCIST therapeutic response assessments in digital PET/CT

Background[18F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs’ quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [18F]FDG PET solid tumour treatment response assessments, while comparing “standard PET” to “AI denoised half-duration PET” (“AI PET”) during follow-up.Results110 patients referred for baseline and follow-up standard digital [18F]FDG PET/CT were prospectively included. “Standard” EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a “gold standard” were compared to “mixed” classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to “UHD”) or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTCUHD or EARL2 or PERCISTUHD or EARL2 mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen’s kappa = 0.86 (95% CI: 0.78–0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients.ConclusionsAlthough comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [18F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory.

The Influence of Circulating Immune Cell and CA125 Dynamics on Neoadjuvant Therapy Selection for Advanced Ovarian Cancer.

Background and Objectives: Ovarian cancer, including tubal and peritoneal cancer, is the third most common gynecological cancer and the leading cause of death from gynecological malignancies in developed countries. This study explores the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in determining the optimal duration of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. It also investigates the correlation between NLR dynamics and the KELIM score, a chemosensitivity marker, to enhance individualized therapeutic strategies. Materials and Methods: A total of 79 patients underwent NACT followed by interval debulking surgery (IDS) or palliative care. The data collected included demographic information, tumor characteristics, treatment modalities, and laboratory parameters. The baseline NLR (NLR-T0) and post-therapeutic NLR (NLR-T1) were calculated, and their variation (NLR∆) was analyzed. The KELIM score was determined using CA-125 values. Results: Patients with a high baseline NLR (≥2.5) had significantly worse progression-free survival (PFS) and overall survival (OS) compared to those with a low NLR (<2.5). A negative NLR∆ was associated with poorer PFS and OS. The KELIM score indicated a more effective treatment response, with higher scores correlating with better outcomes. The majority of patients achieved R0 resection, and those with favorable KELIM scores showed improved survival rates. Conclusions: The NLR is a valuable prognostic marker for assessing treatment response and guiding NACT duration in advanced ovarian cancer.

Metabolomic Profiling of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy for Predicting Disease-Free and Overall Survival.

Breast cancer (BC) remains a significant global health concern, with neoadjuvant chemotherapy (NACT) offering preoperative benefits like tumor downstaging and treatment response assessment. However, identifying factors influencing post-NACT treatment response and survival outcomes is challenging. Metabolomic approaches offer promising insights into understanding these outcomes. This study analyzed the serum of 80 BC patients before and after NACT, followed for up to five years, correlating with disease-free survival (DFS) and overall survival (OS). Using untargeted nuclear magnetic resonance (NMR) spectroscopy and a novel statistical model that avoids collinearity issues, we identified metabolic changes associated with survival outcomes. Four metabolites (histidine, lactate, serine, and taurine) were significantly associated with DFS. We developed a metabolite-related survival score (MRSS) from these metabolites, stratifying patients into low- and high-risk relapse groups, independent of classical prognostic factors. High-risk patients had a hazard ratio (HR) for DFS of 3.42 (95% CI 1.51-7.74; p = 0.003) after adjustment for disease stage and age. A similar trend was observed for OS (HR of 3.34, 95% CI 1.64-6.80; p < 0.001). Multivariate Cox proportional hazards analysis confirmed the independent prognostic value of the MRSS. Our findings suggest the potential of metabolomic data, alongside traditional markers, in guiding personalized treatment decisions and risk stratification in BC patients undergoing NACT. This study provides a methodological framework for leveraging metabolomics in survival analyses.

Role and potential of 18F-fluorodeoxyglucose-positron emission tomography-computed tomography in large-vessel vasculitis: a comprehensive review.

Large-vessel vasculitis (LVV) is a group of diseases characterized by inflammation of the aorta and its main branches, which includes giant cell arteritis (GCA), polymyalgia rheumatica (PMR), and Takayasu's arteritis (TAK). These conditions pose significant diagnostic and management challenges due to their diverse clinical presentations and potential for serious complications. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) has emerged as a valuable imaging modality for the diagnosis and monitoring of LVV, offering insights into disease activity, extent, and response to treatment. 18F-FDG-PET-CT plays a crucial role in the diagnosis and management of LVV by allowing to visualize vessel involvement, assess disease activity, and guide treatment decisions. Studies have demonstrated the utility of 18F-FDG-PET-CT in distinguishing between LVV subtypes, evaluating disease distribution, and detecting extracranial involvement in patients with cranial GCA or PMR phenotypes. Additionally, 18F-FDG-PET-CT has shown promising utility in predicting clinical outcomes and assessing treatment response, based on the correlation between reductions in FDG uptake and improved disease control. Future research should focus on further refining PET-CT techniques, exploring their utility in monitoring treatment response, and investigating novel imaging modalities such as PET-MRI for enhanced diagnostic accuracy in LVV. Overall, 18F-FDG-PET-CT represents a valuable tool in the multidisciplinary management of LVV, facilitating timely diagnosis and personalized treatment strategies to improve patient outcomes.

The impact of PET imaging on triple negative breast cancer: an updated evidence-based perspective.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors. It predominantly affects younger women and is associated with a poor prognosis. This systematic review aims to evaluate the current role of positron emission tomography (PET) in the management of TNBC patients and to identify future research directions. We systematically searched the PubMed, Scopus, and Web of Science databases up to February 2024. A team of five researchers conducted data extraction and analysis. The quality of the selected studies was assessed using a specific evaluation form. Twenty-eight studies involving 2870 TNBC patients were included in the review. Key clinical applications of PET in TNBC included predicting pathological complete response (pCR) in patients undergoing neoadjuvant chemotherapy (NAC), assessing the prognostic value of baseline PET, and initial disease staging. Two studies utilized PSMA-ligand agents, while the majority used [18F]FDG-based PET. Significant associations were found between baseline [18F]FDG uptake and molecular biomarkers such as PDL-1, androgen receptor, and Ki67. Baseline [18F]FDG PET led to the upstaging of patients from stage IIB to stage IV, influencing treatment decisions and survival outcomes. In the NAC setting, serial PET scans measuring changes in [18F]FDG uptake, indicated by maximum standardized uptake value (SUVmax), predicted pCR with varying cut-off values correlated with different response rates. Semiquantitative parameters such as metabolic tumor volume (MTV) and PET lung index were prognostic for metastatic disease. In TNBC patients, [18F]FDG PET is essential for initial disease staging in both localized and metastatic settings. It is also useful for assessing treatment response to NAC. The ability of PET to correlate metabolic activity with molecular markers and predict treatment outcomes highlights its potential in TNBC management. Further prospective studies are needed to refine these clinical indications and establish its definitive role.

Imaging in Musculoskeletal TB

AbstractTuberculosis (TB) remains a significant global health challenge, with musculoskeletal TB accounting for a notable proportion of cases. The spine is the most commonly affected site, followed by the hip, knee, and ankle joints. Prompt and accurate diagnosis is essential to prevent joint destruction, deformity, and neurological complications. Given the paucibacillary nature of musculoskeletal TB, imaging plays a pivotal role in diagnosis, guiding sampling procedures, and assessing treatment response. Contrast-enhanced magnetic resonance imaging has emerged as the preferred modality for diagnosing and monitoring both spinal and extraspinal TB. This review provides an in-depth analysis of imaging characteristics of musculoskeletal TB, highlighting key findings essential for early diagnosis and differentiation from similar pathologies. Through case-based illustrations, various anatomical locations of osteoarticular TB are discussed.

Second harmonic generation digital pathology with artificial intelligence: breakthroughs in studying fibrosis dynamics and treatment response

Fibrosis represents a highly conserved response to tissue injury. Assessing fibrosis is central in diagnostic pathology, evaluating treatment response and prognosis. Second harmonic generation digital pathology with artificial intelligence analyses provides unparalleled precision and granularity in quantifying tissue collagen in its natural, unstained environment.. This technology reveals new insights into the balance between fibrogenesis and fibrolysis, crucial in tracking disease evolution and treatment outcomes. This review describes applications of second harmonic generation digital pathology with artificial intelligence for detailed characterization of liver fibrosis, assessing treatment response in clinical trials, analyzing collagen features in other chronic diseases and cancers. Additionally, it offers a perspective on future developments in integrating various technologies into a comprehensive diagnostic workflow for more effective evaluation of therapy and disease prognosis.

Challenges in Hypophosphatasia: Suspicion, Diagnosis, Genetics, Management, and Follow-Up.

Hypophosphatasia (HPP) is a rare genetic disorder caused by loss-of-function variants in the ALPL gene, leading to deficient tissue-nonspecific alkaline phosphatase (ALP) activity. This results in a distinctive biochemical profile marked by low serum ALP levels and elevated pyridoxal-5-phosphate (PLP). The clinical spectrum of HPP ranges from perinatal lethality to asymptomatic cases, presenting significant diagnostic and therapeutic challenges. Diagnosis of HPP relies on identifying the characteristic biochemical signature (low ALP, high PLP), concomitant with skeletal (osteomalacia, rickets, pseudofracture) or extraskeletal (muscle weakness, musculoskeletal pain, dental) manifestations. Current diagnostic frameworks lack uniformity, highlighting the imperative for a standardized diagnostic approach. Molecular genetic testing plays a pivotal role in making the diagnosis of HPP, but difficulties persist in diagnosing milder cases and correlating genotypes with phenotypes. Comprehensive multidisciplinary care is indispensable, with enzyme replacement therapy (ERT) proving efficacious in severe cases and more nuanced management approaches for milder presentations. Overcoming challenges in ERT initiation, treatment response assessment, dose titrations, and long-term surveillance necessitates further refinement of management guidelines. Mild forms of HPP and asymptomatic carriers of pathogenic ALPL variants pose substantial diagnosis and management challenges. Developing consensus-driven guidelines is crucial to enhance clinical outcomes and patient care.

New insights on hidradenitis suppurativa phenotypes and treatment response: An exploratory automated analysis of the SUNSHINE and SUNRISE trials.

Defining hidradenitis suppurativa (HS) subtypes was previously limited by small sample sizes and poor interrater reliability; no study has investigated subtype treatment responses. The objective of this analysis was to characterize HS clusters in adult patients with moderate to severe HS and evaluate secukinumab treatment responses between clusters. Clusters were identified via an unsupervised machine learning clustering analysis using baseline data from the randomized, placebo-controlled SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) phase 3 trials. To assess treatment responses, patients received secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W) or placebo, for 16 weeks, after which, placebo patients randomly switched to SECQ2W/SECQ4W, and SECQ2W/SECQ4W patients maintained their original treatment, until week 52. Baseline outcomes included patient characteristics, disease characteristics and severity, HS-associated comorbidities and previous treatment exposures. Treatment response was assessed via the HS clinical response (HiSCR), abscess and inflammatory nodule (AN) count, flares and NRS30 (skin pain). Based on baseline data, three clusters were identified from 1084 patients (Cluster 1: 54.1%, Cluster 2: 17.8%, Cluster 3: 28.1%). Cluster 1 was predominantly female (65.4%) and was characterized by milder HS. Cluster 2 had more patients from the Asia Pacific, Middle East and Africa region (58.5%) and was characterized by moderate HS. Cluster 3 had the highest rates of previous exposure to biologics (45.9%) and prior HS-related surgeries (47.5%) and was characterized by severe HS. SECQ2W and SECQ4W demonstrated efficacy versus placebo in all clusters at week 16; SECQ2W and SECQ4W efficacy was maintained to week 52. SECQ2W treatment showed a trend for greater efficacy versus SECQ4W in Cluster 3 through week 52. Three HS clusters were identified. Secukinumab demonstrated benefit over placebo in all clusters. However, patients with more severe disease may take longer to respond and more frequent secukinumab dosing may be required for these patients. SUNSHINE (NCT03713619) and SUNRISE (NCT03713632).

Post-Chemotherapy Canine Lymphomatous Lymph Node Observations on B-Mode and Strain Elastographic Ultrasound.

Canine multicentric lymphoma (CML) is a prevalent hematopoietic neoplasm that initially responds well to treatment but often relapses due to chemotherapy resistance. Evaluation of treatment response is essential for effective management. Ultrasound (US) can differentiate between benign and lymphomatous lymph nodes (LLNs). However, its utility in monitoring LLNs post chemotherapy is limited. This study aimed to compare US parameters of LLNs during the first 3 weeks post treatment and evaluate their diagnostic performance compared with the conventional method for assessing treatment response. This study included 95 LLNs from 15 dogs with CML and 60 normal lymph nodes (NLNs) from 15 healthy dogs. US, including B-mode and elastography, was performed pre-treatment and weekly for 3 weeks post treatment, and compared with the results of NLNs. LLNs were categorized into partial response and stable disease groups using the conventional method. US scores were established by combining B-mode and elastography parameters. The results showed significantly higher values of LLNs in the short-to-long axis ratio, elastographic scales, and blue-to-green color histogram compared with NLNs. Additionally, LLNs at pre-treatment had significantly higher values than LLNs post treatment. US scores significantly differed among the healthy, partial response, and stable disease groups. In conclusion, B-mode US, elastography, and US scores demonstrated changes during chemotherapy consistent with the conventional method and can be used in conjunction with the conventional method to evaluate the treatment response of CML.

Role of optical coherence tomography angiography in retinal tumors: A narrative review.

Intraocular tumors constitute a small subset of cases in ophthalmologic practice. Proper diagnosis of intraocular tumors is crucial because some pose threat to vision and life, while others may indicate underlying systemic disorders. Intraocular tumors comprise benign and malignant lesions affecting the retina, choroid, optic disc, iris, and ciliary body. Retinal tumors can be classified as vascular, neural, glial, and retinal pigment epithelial tumors. Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality employed in diagnosis and management of retinal and choroidal vascular diseases, and has enhanced our knowledge in better understanding of the vascular physiology and pathology. Multiple case reports and small series evaluating the role of OCTA in retinal tumors are published in literature. OCTA helps in better understanding of the vascularity of intraocular tumors. In addition to this, OCTA has its role in clinical practice. It helps in identification of small retinal capillary hemangioblastoma (RCH), assessment of treatment response, and identification of tumor recurrence in RCH. It aids in identification of retinal astrocytic hamartoma missed on clinical examination and differentiating retinal astrocytic hamartoma and presumed solitary circumscribed retinal astrocytic proliferation. It helps in assessment of risk of tumor recurrence in retinoblastoma. It helps in differentiating tumors of retinal pigment epithelium (RPE) origin from pigmented tumors of the choroid. It also helps in detection of choroidal neovascular membrane in combined hamartoma of the retina and RPE.

AB062. Investigating miR-21 as a non-invasive prognostic biomarker in glioma patients.

Glioma prognosis remains a challenge due to its high recurrence and resistance to treatment. Diagnosis and follow-up in resource-constrained regions often lead to significant patient attrition. Serum microRNAs (miRNAs) are seen to be aberrantly expressed in malignancies can be found in tumor tissues and peripheral samples. This offers a pathway for non-invasive liquid biopsies. miR-21 is an established biomarker for glioma prognosis, which needs to be validated in our population. We collected 89 intraoperative tumor tissue samples, and 42 pre- and post-operative serum samples from glioma patients, ten control tissues, eight healthy serum samples and analysed for miR-21 expression through quantitative polymerase chain reaction (qPCR) analysis. Correlational analysis with molecular markers isocitrate dehydrogenase (IDH), Ki-67, ATRX, p53, and survival curves through the Kaplan-Meier method were calculated in high and low miR-21 expression groups. The hazard ratio was quantitatively determined using Cox regression analysis, considering both univariate associations and multivariate correlations with clinical parameters. miR-21 expression in tissue was significantly upregulated with increase of glioma grades (P<0.001) and in patients above 50 years (P=0.003) age group. Whereas no gender bias was seen in its expression pattern. Its expression did not show any correlation with tumor volume (r=0.22, P=0.08). A similar expression pattern of miR-21 was observed in serum samples of glioma. IDH-wildtype (P=2.06e-03) and high Ki-67 (P=2.50e-03) patient group showed significant upregulation of miR-21 expression compared to IDH-mutant and low Ki-67 group. Patients with low miR-21 expression had significantly longer overall survival (OS) than patients with high miR-21 expression (P =0.006). Similarly, quantitative hazard analysis indicates that patients in the high expression group have 2.77 times higher risk of mortality [95% confidence interval (CI): 0.19-0.92], in comparison to patients in the low expression group (P=0.008). Our findings validate the utility of miR-21 as a prognostic serum biomarker to help diagnose and assess treatment response in advancing glioma grades, within our population.

Cytokine analysis of aqueous humor in patients with cytomegalovirus corneal endotheliitis.

To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response.

Update on Pathologic Conditions, Imaging Findings, Prevention, and Management of Human Papillomavirus-related Neoplasms.

Human papillomavirus (HPV) is the most common sexually transmitted infection that proliferates in the squamous epithelium and is the most common source of viral-related neoplasms. Low-risk subtypes (HPV-6 and -11) cause respiratory papillomas (laryngeal, tracheal, and bronchial) and condyloma acuminata of the penis, anus, and perineal region (anogenital warts). High-risk subtypes (HPV-16, -18, -31, and -33) are responsible for oropharyngeal squamous cell carcinoma (SCC) that involves the tongue base, tonsils, posterior pharyngeal wall, and larynx and malignancies of the anogenital region (cancers of the cervix, vagina, vulva, penis, and anal canal). Recent studies have increasingly shown a favorable treatment response and substantial differences in the overall prognosis associated with HPV-associated oropharyngeal cancers. Given this fact, oropharyngeal, cervical, and penile SCCs are classified as HPV-associated and HPV-independent cancers in the current World Health Organization classification. Imaging is essential in the early detection, diagnosis, and staging of HPV-associated cancers. Imaging also helps assess treatment response and postoperative complications and is used for long-term surveillance. HPV-associated oropharyngeal SCCs have well-defined borders and solid and cystic nodal metastases at imaging. Updated screening and vaccination guidelines are currently available that have great potential to decrease the overall disease burden and help control this worldwide public health concern. Novel therapeutic strategies, such as immunotherapies, are being explored, and imaging biomarkers that can predict treatment response and prognosis are being investigated; radiologists play a pivotal role in these efforts. ©RSNA, 2024 Supplemental material is available for this article.

Evaluation of treatment response with serial CT in patients with non-tuberculous mycobacterial pulmonary disease.

In patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD), the response to treatment is evaluated based on microbiological, clinical, and radiological data. However, little is known about the dynamics of CT findings. The aim of this study was to evaluate CT changes in NTM-PD in order to define radiological criteria for treatment success. Retrospective multicenter study (Hannover, Heidelberg, Gauting). Sixty patients with NTM-PD and at least two consecutive CT scans were included. Scoring for NTM-PD was performed by evaluating variables of bronchiectasis, mucus plugging, bronchiolitis, cavities, nodules, and consolidations on an ordinal scale from 0 to 3. Differences between baseline and follow-up were calculated, and patients with/without cultural conversion were compared using the Mann-Whitney U-test. For paired comparison of the two consecutive CT scans the Wilcoxon test was used. Comparing patients with and without culture conversion, there were significant differences in temporal changes of bronchiectasis (p < 0.001), cavities (p = 0.006), bronchiolitis (p < 0.001), consolidations (p = 0.004), and total score (p < 0.001). Nodules showed no significant differences between groups (p = 0.060). The Wilcoxon test showed significant differences between both CTs in patients with a microbiological cure for the total score (p < 0.001), cavities (p = 0.005), bronchiolitis (p < 0.001), and consolidations (p = 0.021) with a decrease after microbiological cure, whereas bronchiectasis (p = 0.102) and nodules (p = 0.18) stayed stable. In the case of persistently positive cultures, there was an increase in the total score (p = 0.010) which was attributable to progressivebronchiectasis (p < 0.001). Cavities, consolidations, and bronchiolitis are useful to assess treatment response, whereas bronchiectasis and nodules may remain stable despite successful treatment. Cavities, consolidations, and bronchiolitis can assess treatment response whereas bronchiectasis and nodules may remain stable despite successful treatment. In persistently positive cultures, bronchiectasis showed an increase over time indicating that NTM-PD is a progressive chronic disease. Little is known about CT changes in nontuberculous mycobacteriapulmonary disease (NTM-PD) and criteria to evaluate treatment response. In the case of culture conversion, cavities and bronchiolitis decreased whereas bronchiectasis and nodules remained stable. Cavities and bronchiolitis can evaluate treatment response in NTM, but bronchiectasis and nodules may persist despite successful treatment.