Dandy-Walker Phenotype with Brainstem Involvement: 2 Distinct Subgroups with Different Prognosis.

BACKGROUND AND PURPOSE: Although cardinal imaging features for the diagnostic criteria of the Dandy-Walker phenotype have been recently defined, there is a large range of unreported malformations among these patients. The brainstem, in particular, deserves careful attention because malformations in this region have potentially important implications for clinical outcomes. In this article, we offer detailed information on the association of brainstem dysgenesis in a large, multicentric cohort of patients with the Dandy-Walker phenotype, defining different subtypes of involvement and their potential clinical impact. MATERIALS AND METHODS: In this established multicenter cohort of 329 patients with the Dandy-Walker phenotype, we include and retrospectively review the MR imaging studies and clinical records of 73 subjects with additional brainstem malformations. Detailed evaluation of the different patterns of brainstem involvement and their potential clinical implications, along with comparisons between posterior fossa measurements for the diagnosis of the Dandy-Walker phenotype, was performed among the different subgroups of patients with brainstem involvement. RESULTS: There were 2 major forms of brainstem involvement in patients with Dandy-Walker phenotype including the following: 1) the mild form with anteroposterior disproportions of the brainstem structures "only" (57/73; 78%), most frequently with pontine hypoplasia (44/57; 77%), and 2) the severe form with patients with tegmental dysplasia with folding, bumps, and/or clefts (16/73; 22%). Patients with severe forms of brainstem malformation had significantly increased rates of massive ventriculomegaly, additional malformations involving the corpus callosum and gray matter, and interhemispheric cysts. Clinically, patients with the severe form had significantly increased rates of bulbar dysfunction, seizures, and mortality. CONCLUSIONS: Additional brainstem malformations in patients with the Dandy-Walker phenotype can be divided into 2 major subgroups: mild and severe. The severe form, though less prevalent, has characteristic imaging features, including tegmental folding, bumps, and clefts, and is directly associated with a more severe clinical presentation and increased mortality.

5-Fluorouracil-Loaded PLGA Nanoparticles: Formulation, Physicochemical Characterisation, and In VitroAnti-Cancer Activity.

The major goal of this investigation was to prepare a drug delivery of polymeric nanoparticles (NPs) from 5-fluorouracil (FU) that could be delivered intravenously and improve the therapeutic index of the FU. In order to achieve this, interfacial deposition method was used to prepare FU entrapped poly-(lactic-co-glycolic acid) nanoparticles (FU-PLGA-NPs). The influence of various experimental settings on the effectiveness of FU integration into the NPs was assessed. Our findings show that the technique used to prepare the organic phase and the ratio of the organic phase to the aqueous phase had the greatest impact on the effectiveness of FU integration into NPs. The results show that the preparation process produced spherical, homogenous, negatively charged particles with a nanometric size of 200 nm that are acceptable for intravenous delivery. A quick initial release over 24 h and then slow and steady release of FU from the formed NPs, exhibiting a biphasic pattern. Through the human small cell lung cancer cell line (NCI-H69), the in vitro anti-cancer potential of the FU-PLGA-NPs was evaluated. It was then associated to the in vitro anti-cancer potential of the marketed formulation Fluracil®. Investigations were also conducted into Cremophor-EL (Cre-EL) potential activity on live cells. The viability of NCI-H69 cells was drastically reduced when they were exposed to 50 µg·mL-1 Fluracil®. Our findings show that the integration of FU in NPs significantly increases the drug cytotoxic effect in comparison to Fluracil®, with this potential effect being particularly important for extended incubation durations.

Refining the Neuroimaging Definition of the Dandy-Walker Phenotype.

BACKGROUND AND PURPOSE: The traditionally described Dandy-Walker malformation comprises a range of cerebellar and posterior fossa abnormalities with variable clinical severity. We aimed to establish updated imaging criteria for Dandy-Walker malformation on the basis of cerebellar development. MATERIALS AND METHODS: In this multicenter study, retrospective MR imaging examinations from fetuses and children previously diagnosed with Dandy-Walker malformation or vermian hypoplasia were re-evaluated, using the choroid plexus/tela choroidea location and the fastigial recess shape to differentiate Dandy-Walker malformation from vermian hypoplasia. Multiple additional measures of the posterior fossa and cerebellum were also obtained and compared between Dandy-Walker malformation and other diagnoses. RESULTS: Four hundred forty-six examinations were analyzed (174 fetal and 272 postnatal). The most common diagnoses were Dandy-Walker malformation (78%), vermian hypoplasia (14%), vermian hypoplasia with Blake pouch cyst (9%), and Blake pouch cyst (4%). Most measures were significant differentiators of Dandy-Walker malformation from non-Dandy-Walker malformation both pre- and postnatally (P < .01); the tegmentovermian and fastigial recess angles were the most significant quantitative measures. Posterior fossa perimeter and vascular injury evidence were not significant differentiators pre- or postnatally (P > .3). The superior posterior fossa angle, torcular location, and vermian height differentiated groups postnatally (P < .01), but not prenatally (P > .07). CONCLUSIONS: As confirmed by objective measures, the modern Dandy-Walker malformation phenotype is best defined by inferior predominant vermian hypoplasia, an enlarged tegmentovermian angle, inferolateral displacement of the tela choroidea/choroid plexus, an obtuse fastigial recess, and an unpaired caudal lobule. Posterior fossa size and torcular location should be eliminated from the diagnostic criteria. This refined phenotype may help guide future study of the numerous etiologies and varied clinical outcomes.

Cellular Density in Adult Glioma, Estimated with MR Imaging Data and a Machine Learning Algorithm, Has Prognostic Power Approaching World Health Organization Histologic Grading in a Cohort of 1181 Patients.

BACKGROUND AND PURPOSE: Recent advances in machine learning have enabled image-based prediction of local tissue pathology in gliomas, but the clinical usefulness of these predictions is unknown. We aimed to evaluate the prognostic ability of imaging-based estimates of cellular density for patients with gliomas, with comparison to the gold standard reference of World Health Organization grading. MATERIALS AND METHODS: Data from 1181 (207 grade II, 246 grade III, 728 grade IV) previously untreated patients with gliomas from a single institution were analyzed. A pretrained random forest model estimated voxelwise tumor cellularity using MR imaging data. Maximum cellular density was correlated with the World Health Organization grade and actual survival, correcting for covariates of age and performance status. RESULTS: A maximum estimated cellular density of >7681 nuclei/mm2 was associated with a worse prognosis and a univariate hazard ratio of 4.21 (P < .001); the multivariate hazard ratio after adjusting for covariates of age and performance status was 2.91 (P < .001). The concordance index between maximum cellular density (adjusted for covariates) and survival was 0.734. The hazard ratio for a high World Health Organization grade (IV) was 7.57 univariate (P < .001) and 5.25 multivariate (P < .001). The concordance index for World Health Organization grading (adjusted for covariates) was 0.761. The maximum cellular density was an independent predictor of overall survival, and a Cox model using World Health Organization grade, maximum cellular density, age, and Karnofsky performance status had a higher concordance (C = 0.764; range 0.748-0.781) than the component predictors. CONCLUSIONS: Image-based estimation of glioma cellularity is a promising biomarker for predicting survival, approaching the prognostic power of World Health Organization grading, with added values of early availability, low risk, and low cost.

Synthesis of hydroxyapatite nanoparticles using Acacia falcata leaf extract and study of their anti-cancerous activity against cancerous mammalian cell lines.

This study deals with the synthesis of hydroxyapatite nanoparticles (HAPnps) mediated by Acacia falcata leaf extract. Aggregates of needle-shaped crystalline nanostructures were confirmed by FE-SEM and TEM analysis. Well-defined rings in the SAED patterns corroborated the polycrystalline nature of the HAPnps. Individual elements present in the HAPnps were attested by the specific signals for Ca, P, and O in the EDS and XPS analyses. The distinct peaks observed in the XRD spectrum matched well with the HAP hexagonal patterns with a mean crystallite size of 55.04 nm. The FTIR study unveiled the coating of the nanoparticles with the biomolecules from Acacia falcata leaves. The suspension HAPnps exhibited polydispersity (0.446) and remarkable stability (zeta potential: - 31.9 mV) as evident from DLS studies. The pore diameter was 25.7 nm as obtained from BET analysis, suggesting their mesoporous nature. The HAPnps showed the cytotoxic effect on A549 lung and MDA-MB231 breast carcinoma cell lines, with an IC50 value of 55 µg/mL. The distortion of the cell membrane and cell morphology, along with the chromatin condensation and cell necrosis on treatment with HAPnps were detected under fluorescence microscopy post acridine orange/ethidium bromide dye staining. This study reports the anti-cancerous potential of non-drug-loaded plant-mediated HAPnps. Therefore, the HAPnps obtained in this investigation could play a vital role in the biomedical field of cancer therapy.

Antidiabetic Effect of Tamarindus indica and Momordica charantia and Downregulation of TET-1 Gene Expression by Saroglitazar in Glucose Feed Adipocytes and Their Involvement in the Type 2 Diabetes-Associated Inflammation In Vitro.

To date, there is no satisfactory and effective therapy available to cure type 2 diabetes mellitus (T2DM). This present work is focused on plant extracts and the effect of saroglitazar and TET genes on oxidative stress and inflammation in vitro adipocytes. Aqueous extracts of Tamarindus indica and Momordica charantia seed have shown potent antidiabetic activity that decreases glucose levels in diabetic adipocytes. After seven and fourteen days, the sugar level in the blood was significantly reduced when plant extracts were supplemented. Lipid profiles including total cholesterol (TC), triglyceride (TGL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) showed a highly significant change as expected in adipocytes treated with glucose compared with controlled adipocytes (P < 0.001). Gene expression of catalase, superoxide dismutase (SOD1, SOD2), and glutathione peroxidase (GPx) are changed twice, thrice, and quadruplet, respectively. The level of interleukin-1 (IL1) and tumor necrosis factor-α (TNF-α) was restored but the interleukin-6 (IL6) and ten-eleven-translocation-1 (TET1) were completely knocked down by the use of saroglitazar. In comparison with the diabetic group, this supplementation significantly increased glycogen content and glucose-6-phosphate dehydrogenase activity. In the extract supplemented group, glucose-6-phosphatase, glucose-oxidizing enzyme, and glucose-phosphorylating enzyme activities were significantly reduced. After seven days of extract supplementation, these parameters were not resettled to a controlled level; however, after 14 days of supplementation, all parameters were restored to the control level. In addition to altering gene expression, TET enzymes may contribute to altered adiposity and its metabolic consequences. The purpose of this study is to examine new ideas and approaches for treating obesity, T2DM, and other associated metabolic disorders.

Dermatological Research in India: A Brief Bibliometric Analysis of Publications During 1999-2019.

Background: Dermatology is the science of the skin. In India, dermatology came into picture in the twentieth century. Today's dermatology practiced in India is the modern approach developed and established in western countries based on western medical theory, knowledge, experience, and results from study. Growth of dermatology field in India has progressed since two to three decades. This paper assesses the contributions made by India in the dermatology field by analyzing the total number of publications in top dermatological journals. Materials and Methods: SCImago Journal Rank indicator (2019) was used to search for top dermatology journals and publication metrics was recorded from respective journal websites. Simple statistics tools were used to determine the number of publications during this 20-year period. Results: From 1999 to 2019, there were 547 publications from India, in the top dermatologic journals. It was noted that, original research article contributes maximum number of documents (136). Journal of Dermatology had a maximum number of publications with 174 when compared to other journals. Postgraduate Institute of Medical Education and Research, Chandigarh' had a maximum number of publication (150). Conclusion: The last 20 years have seen a massive increase in the field of dermatology. Today, dermatology is a well-developed field in India. From 1999 to 2019, there is an increase in the trend of publications along with the collaborative publications in the top dermatologic journals. This show the encouraging trend in terms of publications from India in past 20 years.

Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination.

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.

Patients' views on a proposed oral cancer screening technology.

Brush cytology and telemedicine platforms are used with proven benefits in remote diagnosis of malignancies like cervical cancer. In low-resource settings access to the current standard of care, biopsy and histopathology grading of oral lesions, can be unfeasible. Risk-stratifying early malignant and oral potentially-malignant lesions can help instigate therapeutic treatment and improve prognosis. Therefore, a telecytology platform enabling remote connectivity to specialist centres may aid early detection of oral cancer. We outline head and neck (H&N) cancer patients' views on an oral brush cytology investigation.

Safety, immunogenicity, and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates.

Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, effective vaccines are essential to control the current coronavirus disease 2019 (COVID-19) pandemic. Plant-derived virus-like particle (VLP) vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza. Here, we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein (CoVLP) vaccine candidate formulated with or without Adjuvant System 03 (AS03) or cytidine-phospho-guanosine (CpG) 1018. Although a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses, booster immunization (at 28 days after priming) and adjuvant administration significantly improved both responses, with higher immunogenicity and protection provided by the AS03-adjuvanted CoVLP. Fifteen micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2 (IL-2)-driven response and IL-4 expression in CD4 T cells. Animals were challenged by multiple routes (i.e., intratracheal, intranasal, and ocular) with a total viral dose of 106 plaque-forming units of SARS-CoV-2. Lower viral replication in nasal swabs and bronchoalveolar lavage fluid (BALF) as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with AS03. No clinical, pathologic, or virologic evidence of vaccine-associated enhanced disease was observed in vaccinated animals. The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

Changes in stroke volume variation and cardiac index during open major bowel surgery.

BACKGROUND: Stroke volume variation (SVV) is a dynamic indicator of preload, which is a determinant of cardiac output. Aims: Aim of this study was to evaluate the relationship between changes in SVV and cardiac index (CI) in patients with normal left ventricular function undergoing major open abdominal surgery. PATIENTS AND METHODS: Patients undergoing major open abdominal surgery were monitored continuously with FloTrac® to measure SVV and CI along with standard monitoring. Both SVV and CI were noted at baseline and every 10 min thereafter till the end of surgery and were observed for concurrence between the measurements. RESULTS: 1800 pairs of measurement of SVV and CI were obtained from 60 patients. Mean SVV and CI (of all patients) measured at different time points of measurement showed that as SVV increased with time, the CI dropped correspondingly. When individual readings of CI and SVV were plotted against each other, the scatter was found to be wide, reiterating the lack of agreement between the two parameters (R2 = 0.035). SVV >13% suggesting hypovolemia was found at 207 time points. Of these, 175 had a CI >2.5 L/min/m2 and only 32 patients had a CI <2.5 L/min/m2. CONCLUSION: SVV, a dynamic index of fluid responsiveness can be used to monitor patients expected to have large fluid shifts during major abdominal surgery. It is very specific and has a high negative predictive value. When SVV increases, CI is usually maintained. Since many factors affect SVV and CI, any increase in SVV >13%, must be correlated with other parameters before administration of the fluid challenge.

On detour index of cycloparaphenylene and polyphenylene molecular structures.

Cycloparaphenylene is a particle that comprises a few benzene rings associated with covalent bonds in the para positions to frame a ring-like structure. Similarly, poly (para-phenylenes) are macromolecules that include benzenoid compounds straightforwardly joined to each other by C-C bonds. Because of their remarkable architectural highlights, these structures have fascinated attention from numerous vantage focuses. Descriptors are among the most fundamental segments of prescient quantitative structure-activity and property relationship (QSAR/QSPR) demonstrating examination. They encode chemical data of particles as quantitative numbers, which are utilized to create a mathematical correlation. The nature of a predictive model relies upon great demonstrating insights, yet additionally on the extraction of compound highlights. To a great extent, Molecular topology has exhibited its adequacy in portraying sub-atomic structures and anticipating their properties. It follows a two-dimensional methodology, just thinking about the interior plan, including molecules. Explicit subsets speak the design of every atom of topological descriptors. When all around picked, these descriptors give a unique method of describing an atomic system that can represent the most significant highlights of the molecular structure. Detour index is one such topological descriptor with much application in chemistry, especially in QSAR/QSPR studies. This article presents an exact analytical expression for the detour index of cycloparaphenylene and poly (para-phenylene).

E-pharmacophore based screening to identify potential HIV-1 gp120 and CD4 interaction blockers for wild and mutant types.

HIV-1 gp120 provides a multistage viral entry process through the conserved CD4 binding site. Hunting of potential blockers can diminish the interaction of gp120 with the CD4 host receptor leading to the suppression of HIV-1 infection. Structure-based pharmacophore virtual screening followed by binding free energy calculation, molecular dynamics (MD) simulation and density functional theory (DFT) calculation is applied to discriminate the potential blockers from six small molecule databases. Five compounds from six databases exhibited vital interactions with key residues ASP368, GLU370, ASN425, MET426, TRP427 and GLY473 of gp120, involved in the binding with CD4, host receptor. Most importantly, compound NCI-254200 displayed strong communication with key residues of wild type and drug resistance single mutant gp120 (M426L and W427V) even in the dynamic condition, evidenced from MD simulation. This investigation provided a potential compound NCI-254200 which may show inhibitory activity against HIV-1 gp120 variant interactions with CD4 host cell receptors.

Long-term outcomes of index cryoballoon ablation or point-by-point radiofrequency ablation in patients with atrial fibrillation and systolic heart failure.

Catheter ablation is an established effective approach for the treatment of atrial fibrillation (AF) in patients with heart failure, however, the role of cryoablation in this setting is unclear. Procedural success and left ventricular systolic dysfunction (LVEF) improvement in patients with LVEF ≤ 45% undergoing index catheter ablation with cryoablation were evaluated. Freedom from AF recurrence was seen in 43% rising to 59% following repeat procedure. There were significant improvements in LVEF and functional status at long-term follow-up. Results were comparable to a contemporaneous cohort of heart failure patients undergoing index ablation with radiofrequency ablation. Cryoablation is an effective first-line AF ablation approach in the setting of heart failure.

Estimating Local Cellular Density in Glioma Using MR Imaging Data.

BACKGROUND AND PURPOSE: Increased cellular density is a hallmark of gliomas, both in the bulk of the tumor and in areas of tumor infiltration into surrounding brain. Altered cellular density causes altered imaging findings, but the degree to which cellular density can be quantitatively estimated from imaging is unknown. The purpose of this study was to discover the best MR imaging and processing techniques to make quantitative and spatially specific estimates of cellular density. MATERIALS AND METHODS: We collected stereotactic biopsies in a prospective imaging clinical trial targeting untreated patients with gliomas at our institution undergoing their first resection. The data included preoperative MR imaging with conventional anatomic, diffusion, perfusion, and permeability sequences and quantitative histopathology on biopsy samples. We then used multiple machine learning methodologies to estimate cellular density using local intensity information from the MR images and quantitative cellular density measurements at the biopsy coordinates as the criterion standard. RESULTS: The random forest methodology estimated cellular density with R 2 = 0.59 between predicted and observed values using 4 input imaging sequences chosen from our full set of imaging data (T2, fractional anisotropy, CBF, and area under the curve from permeability imaging). Limiting input to conventional MR images (T1 pre- and postcontrast, T2, and FLAIR) yielded slightly degraded performance (R2 = 0.52). Outputs were also reported as graphic maps. CONCLUSIONS: Cellular density can be estimated with moderate-to-strong correlations using MR imaging inputs. The random forest machine learning model provided the best estimates. These spatially specific estimates of cellular density will likely be useful in guiding both diagnosis and treatment.

T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers.

Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to elicit nAbs and cellular immunity, including CD8+ tissue-resident memory T cells. After ten vaginal challenges with autologous virus, protection was observed in both vaccine groups at 53.3% and 66.7%, respectively. A nAb titer >300 was generally associated with protection but in the heterologous viral vector + nAb group, titers <300 were sufficient. In this group, protection was durable as the animals resisted six more challenges 5 months later. Antigen stimulation of T cells in ex vivo vaginal tissue cultures triggered antiviral responses in myeloid and CD4+ T cells. We propose that cellular immune responses reduce the threshold of nAbs required to confer superior and durable protection.

Imaging-Based Algorithm for the Local Grading of Glioma.

BACKGROUND AND PURPOSE: Gliomas are highly heterogeneous tumors, and optimal treatment depends on identifying and locating the highest grade disease present. Imaging techniques for doing so are generally not validated against the histopathologic criterion standard. The purpose of this work was to estimate the local glioma grade using a machine learning model trained on preoperative image data and spatially specific tumor samples. The value of imaging in patients with brain tumor can be enhanced if pathologic data can be estimated from imaging input using predictive models. MATERIALS AND METHODS: Patients with gliomas were enrolled in a prospective clinical imaging trial between 2013 and 2016. MR imaging was performed with anatomic, diffusion, permeability, and perfusion sequences, followed by image-guided stereotactic biopsy before resection. An imaging description was developed for each biopsy, and multiclass machine learning models were built to predict the World Health Organization grade. Models were assessed on classification accuracy, Cohen κ, precision, and recall. RESULTS: Twenty-three patients (with 7/9/7 grade II/III/IV gliomas) had analyzable imaging-pathologic pairs, yielding 52 biopsy sites. The random forest method was the best algorithm tested. Tumor grade was predicted at 96% accuracy (κ = 0.93) using 4 inputs (T2, ADC, CBV, and transfer constant from dynamic contrast-enhanced imaging). By means of the conventional imaging only, the overall accuracy decreased (89% overall, κ = 0.79) and 43% of high-grade samples were misclassified as lower-grade disease. CONCLUSIONS: We found that local pathologic grade can be predicted with a high accuracy using clinical imaging data. Advanced imaging data improved this accuracy, adding value to conventional imaging. Confirmatory imaging trials are justified.

Cholic Acid-Peptide Conjugates as Potent Antimicrobials against Interkingdom Polymicrobial Biofilms.

Interkingdom polymicrobial biofilms formed by Gram-positive Staphylococcus aureus and Candida albicans pose serious threats of chronic systemic infections due to the absence of any common therapeutic target for their elimination. Herein, we present the structure-activity relationship (SAR) of membrane-targeting cholic acid-peptide conjugates (CAPs) against Gram-positive bacterial and fungal strains. Structure-activity investigations validated by mechanistic studies revealed that valine-glycine dipeptide-derived CAP 3 was the most effective broad-spectrum antimicrobial against S. aureus and C. albicans CAP 3 was able to degrade the preformed single-species and polymicrobial biofilms formed by S. aureus and C. albicans, and CAP 3-coated materials prevented the formation of biofilms. Murine wound and catheter infection models further confirmed the equally potent bactericidal and fungicidal effect of CAP 3 against bacterial, fungal, and polymicrobial infections. Taken together, these results demonstrate that CAPs, as potential broad-spectrum antimicrobials, can effectively clear the frequently encountered polymicrobial infections and can be fine-tuned further for future applications.

Dynamic Contrast-Enhanced MRI in Patients with Brain Metastases Undergoing Laser Interstitial Thermal Therapy: A Pilot Study.

BACKGROUND AND PURPOSE: Tumor recurrence is difficult to predict in patients receiving laser ablation for intracranial malignancy. We assessed the efficacy of the initial area under the time-to-signal intensity curve at 60 seconds (iAUC60) from dynamic contrast-enhanced MR imaging in predicting progression-free survival in patients with brain metastases following laser interstitial thermal therapy. MATERIALS AND METHODS: The study population was a consecutive series of patients undergoing laser interstitial thermal therapy for brain metastases. Patient demographics including age, sex, tumor histology, and Karnofsky Performance Scale were collected prospectively. Preoperative, postoperative, and 1-month follow-up dynamic contrast-enhanced MRIs were analyzed. Values of iAUC60 were computed using a trapezoidal rule applied to the time history of contrast uptake over the first 60 seconds postenhancement. The change in iAUC60 (ΔiAUC60) was calculated by taking the difference between the values of iAUC60 from 2 time points. Pearson correlation coefficients were calculated between progression-free survival, defined as the time from laser interstitial thermal therapy to tumor recurrence, and iAUC60 or ΔiAUC60 values. RESULTS: Thirty-three cases of laser interstitial thermal therapy for 32 brain metastases in a cohort of 27 patients were prospectively analyzed. A significant relationship was observed between the values of iAUC60 from postoperative dynamic contrast-enhanced MR imaging and progression-free survival with Pearson correlation (P = .03) and Cox univariate analysis (P = .01). The relationship between preoperative and 1-month follow-up dynamic contrast-enhanced MR imaging was not significantly correlated with progression-free survival. Similarly, no statistically significant relationship was observed with ΔiAUC60 and progression-free survival between any time points. CONCLUSIONS: Progression-free survival is difficult to predict in patients undergoing laser interstitial thermal therapy for brain metastases due to confounding with posttreatment change. iAUC60 extracted from postoperative dynamic contrast-enhanced MR imaging shows promise for accurately prognosticating patients following this operative therapy.