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Egorova, Natalia, Elie Gottlieb, Mohamed Salah Khlif, Neil J. Spratt, and Amy Brodtmann. "Choroid plexus volume after stroke." International Journal of Stroke 14, no. 9 (May 17, 2019): 923–30. http://dx.doi.org/10.1177/1747493019851277.
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Background Cerebrospinal fluid circulation is crucial for the functioning of the brain. Aging and brain pathologies such as Alzheimer’s disease have been associated with a change in the morphology of the ventricles and the choroid plexus. Despite the evidence from animal models that the cerebrospinal fluid system plays an important role in neuroinflammation and the restoration of the brain after ischemic brain injury, little is known about changes to the choroid plexus after stroke in humans. Aims Our goal was to characterize structural choroid plexus changes poststroke. Methods We used an automatic segmentation tool to estimate the volumes of choroid plexus and lateral ventricles in stroke and control participants at three time points (at baseline, 3 and 12 months) over the first year after stroke. We assessed group differences cross-sectionally at each time point and longitudinally. For stroke participants, we specifically differentiated between ipsi- and contra-lesional volumes. Statistical analyses were conducted for each region separately and included covariates such as age, sex, total intracranial volume, and years of education. Results We observed significantly larger choroid plexus volumes in stroke participants compared to controls in both cross-sectional and longitudinal analyses. Choroid plexus volumes did not exhibit any change over the first year after stroke, with no difference between ipsi- and contra-lesional volumes. This was in contrast to the volume of lateral ventricles that we found to enlarge over time in all participants, with more accelerated expansion in stroke survivors ipsi-lesionally. Conclusions Our results suggest that chronic stages of stroke are characterized by larger choroid plexus volumes, but the enlargement likely takes place prior to or very early after the stroke incident.
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Fox, Robert J., Elizabeth Fisher, Jean Tkach, Jar-Chi Lee, Jeffrey A. Cohen, and Richard A. Rudick. "Brain atrophy and magnetization transfer ratio following methylprednisolone in multiple sclerosis: short-term changes and long-term implications." Multiple Sclerosis Journal 11, no. 2 (April 2005): 140–45. http://dx.doi.org/10.1191/1352458505ms1142oa.
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Background: The short-term effect of corticosteroids on MRI measures of multiple sclerosis (MS) is not well understood and may have a significant impact when using these quantitative measures to evaluate disease activity and changes following other therapeutic interventions. Objective: To determine the impact of a course of intravenous methylprednisolone (IVMP) on quantitative measures of disease activity and tissue injury in MS patients. Methods: We prospectively measured brain parenchymal fraction (BPF), magnetization transfer ratio (MTR, lesional and whole brain), and lesion volumes on nine weekly brain MRI studies in ten MS patients receiving a course of IVMP. A group of nine MS patients not receiving IVMP served as controls. Results: In comparison to untreated controls, BPF declined over the eight weeks following IVMP treatment (P<0.02). BPF decline was most prominent in patients with secondary progressive MS (SPMS, P<0.03), and was not seen in relapsing-remitting (RR) MS patients. Short-term change in BPF correlated with baseline BPF (r=0.62, P=0.05) and short-term change in lesional MTR (r=-0.55, P=0.03), but not with change in enhancing lesion volume. Short-term change in lesional MTR inversely correlated with baseline lesional and whole brain MTR (r=-0.79, P=0.04 for both). There was no significant difference between treated and control patients in measures of MTR or T2, T1 or enhancing lesion volumes. Conclusions: Patients with SPMS showed a greater decline in BPF following IVMP than RRMS patients. A correlation between changes in BPF and MTR suggest that these changes are secondary to altered water content within MS lesions. Differential response to a standardized therapeutic intervention in RRMS and SPMS suggests that responses to therapy may differ due to a fundamental pathologic difference between early and late stage MS.
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Xie, Yu, Catherine Oppenheim, Francis Guillemin, Vincent Gautheron, Benjamin Gory, Hélène Raoult, Sébastien Soize, Jacques Felblinger, Gabriela Hossu, and Serge Bracard. "Pretreatment lesional volume impacts clinical outcome and thrombectomy efficacy." Annals of Neurology 83, no. 1 (January 2018): 178–85. http://dx.doi.org/10.1002/ana.25133.
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Stoecklein, Veit, Stephan Wunderlich, Boris Papzov, Hesheng Liu, Michael Schmutzer, Niklas Thon, Christian Schichor, Jörg-Christian Tonn, and Sophia Stoecklein. "NIMG-65. RESTING-STATE FUNCTIONAL MRI DEMONSTRATES DAMAGE TO FUNCTIONAL CONNECTIVITY IN MENINGIOMA PATIENTS WITH PERIFOCAL EDEMA." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi144. http://dx.doi.org/10.1093/neuonc/noab196.563.
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Abstract BACKGROUND Meningiomas are common intracranial tumors which usually carry a benign prognosis. Some meningiomas cause perifocal edema which might indicate that this subset could interfere with normal brain function. Resting-state functional MRI (rsfMRI) can be used to assess whole brain functional connectivity (fc) which can be used as a marker for disease severity in patients with intracranial tumors, as was recently shown by our group in a cohort of glioma patients. In this study, we investigated whether the presence of perifocal edema in preoperative patients with meningioma leads to fc. METHODS Patients with suspected meningioma were prospectively included and functional resting state MRI scans were obtained. The resulting data was processed according to our recently published method and abnormality of fc was quantified for each individual patient. Abnormality of fc was then correlated with tumor and edema volume as well as WHO grade. RESULTS 26 patients (23 WHO grade I, 3 WHO grade II) were included. 13 patients had perifocal edema. There was a highly significant correlation between edema volume and higher abnormality of fc both in the lesional and the contra-lesional hemisphere (r=0.51, p=0.008 and r=0.61, p=0.001). Patients with no perifocal edema showed only very low abnormality of fc. Tumor volume was not correlated with abnormal fc in both the lesional and the contralesional hemispheres (r=0.23, p=0.27 and r=0.28, p=0.17). There was also no significant correlation between WHO grade and abnormality of fc. CONCLUSION RsfMRI showed significant abnormal fc in meningioma patients with perifocal edema in contrast to patients without edema, independent of tumor volume. This demonstrates that the presence of edema but not the tumor volume is relevant for disturbances of fc.
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Singh, Charu, Jack M. Qian, James B. Yu, and Veronica L. Chiang. "Local tumor response and survival outcomes after combined stereotactic radiosurgery and immunotherapy in non–small cell lung cancer with brain metastases." Journal of Neurosurgery 132, no. 2 (February 2020): 512–17. http://dx.doi.org/10.3171/2018.10.jns181371.
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OBJECTIVEConcurrent use of anti-PD-1 therapies with stereotactic radiosurgery (SRS) have been shown to be beneficial for survival and local lesional control in melanoma patients with brain metastases. It is not known, however, if immunotherapy (IT) confers the same outcome advantage in lung cancer patients with brain metastases treated with SRS.METHODSThe authors retrospectively reviewed 85 non–small cell lung cancer (NSCLC) patients with brain metastases who were treated with SRS between January 2006 and December 2016. Thirty-nine PD-L1 antibody–positive patients received anti-PD-1 therapy with SRS (IT group) and 46 patients received chemotherapy (CT) with SRS (CT group). Results were obtained using chi-square, Kaplan-Meier, and Mann-Whitney U tests and Cox regression analyses.RESULTSMedian survival following first radiosurgical treatment in the whole study group was 11.6 months (95% CI 8–15.5 months). Median survival times in the IT group and CT group were 10 months (95% CI 8.3–13.2 months) and 11.6 months (95% CI 7.7–15.6 months), respectively (p = 0.23). A Karnofsky Performance Status (KPS) score < 80 (p = 0.001) and lung-specific molecular marker Graded Prognostic Assessment (lungmol GPA) score < 1.5 (p = 0.02) were found to be predictive of worse survival.Maximal percent lesional shrinkage and time to maximal shrinkage were not significantly different between the CT and IT groups. Of the lesions for which a complete response occurred, 94.8% had pre-SRS volumes < 500 mm3. The amount of lesion shrinkage and time to maximal shrinkage were not different between the IT and CT groups for lesions with volumes < 500 mm3. However, in lesions with volume > 500 mm3, 90% of lesions shrank after radiosurgery in the IT group compared with 47.8% in the CT group (p = 0.001). Median times to initial response and times to maximal shrinkage were faster in the IT group than in the CT group: initial response 49 days (95% CI 33.7–64.3 days) versus 84 days (95% CI 28.1–140 days), p = 0.001; maximal response 105 days (95% CI 59–150 days) versus 182 days (95% CI 119.6–244 days), p = 0.12.CONCLUSIONSUnlike patients with melanoma, patients with NSCLC with brain metastases undergoing SRS showed no significant benefit—either in terms of survival or total amount of lesional response—when anti-PD-1 therapies were used. However, in lesions with volume > 500 mm3, combining SRS with IT may result in a faster and better volumetric response which may be particularly beneficial in lesions causing mass effect or located in neurologically critical locations.
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Summers, Philipp M., David A. Hartmann, Edward S. Hui, Xingju Nie, Rachael L. Deardorff, Emilie T. McKinnon, Joseph A. Helpern, Jens H. Jensen, and Andy Y. Shih. "Functional deficits induced by cortical microinfarcts." Journal of Cerebral Blood Flow & Metabolism 37, no. 11 (January 16, 2017): 3599–614. http://dx.doi.org/10.1177/0271678x16685573.
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Clinical studies have revealed a strong link between increased burden of cerebral microinfarcts and risk for cognitive impairment. Since the sum of tissue damage incurred by microinfarcts is a miniscule percentage of total brain volume, we hypothesized that microinfarcts disrupt brain function beyond the injury site visible to histological or radiological examination. We tested this idea using a mouse model of microinfarcts, where single penetrating vessels that supply mouse cortex were occluded by targeted photothrombosis. We found that in vivo structural and diffusion MRI reliably reported the acute microinfarct core, based on spatial co-registrations with post-mortem stains of neuronal viability. Consistent with our hypothesis, c-Fos assays for neuronal activity and in vivo imaging of single vessel hemodynamics both reported functional deficits in viable peri-lesional tissues beyond the microinfarct core. We estimated that the volume of tissue with functional deficit in cortex was at least 12-fold greater than the volume of the microinfarct core. Impaired hemodynamic responses in peri-lesional tissues persisted at least 14 days, and were attributed to lasting deficits in neuronal circuitry or neurovascular coupling. These data show how individually miniscule microinfarcts could contribute to broader brain dysfunction during vascular cognitive impairment and dementia.
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Genow, A., C. Hummel, G. Scheler, R. Hopfengärtner, M. Kaltenhäuser, M. Buchfelder, J. Romstöck, and H. Stefan. "Epilepsy surgery, resection volume and MSI localization in lesional frontal lobe epilepsy." NeuroImage 21, no. 1 (January 2004): 444–49. http://dx.doi.org/10.1016/j.neuroimage.2003.08.029.
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Goulay, Romain, Mikaël Naveau, Thomas Gaberel, Denis Vivien, and Jérôme Parcq. "Optimized tPA: A non-neurotoxic fibrinolytic agent for the drainage of intracerebral hemorrhages." Journal of Cerebral Blood Flow & Metabolism 38, no. 7 (July 25, 2017): 1180–89. http://dx.doi.org/10.1177/0271678x17719180.
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Intracerebral hemorrhage (ICH) is the most severe form of stroke. Catheter-delivered thrombolysis with recombinant tissue-type plasminogen activator (rtPA) for the drainage of ICH is currently under evaluation in a phase III clinical trial (MISTIE III). However, in a pig model of ICH, in situ fibrinolysis with rtPA was reported to increase peri-lesional edema by promoting N-methyl-D-aspartate (NMDA)-dependent excitotoxicity. In the present study, we engineered a non-neurotoxic tPA variant, OptPA, and investigated its safety and efficacy for in situ fibrinolysis in a rat model of ICH. Magnetic resonance imaging analyses of hematoma and edema volumes, behavioral tasks and histological analyses were performed to measure the effects of treatments. In vitro, OptPA was equally fibrinolytic as rtPA without promoting NMDA-dependent neurotoxicity. In vivo, in situ fibrinolysis using OptPA reduced hematoma volume, like rtPA, but it also reduced the evolution of peri-hematomal neuronal death and subsequent edema progression. Overall, this preclinical study demonstrates beneficial effects of OptPA compared to rtPA for the drainage of ICH.
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Egorova, Natalia, Thijs Dhollander, Mohamed Salah Khlif, Wasim Khan, Emilio Werden, and Amy Brodtmann. "Pervasive White Matter Fiber Degeneration in Ischemic Stroke." Stroke 51, no. 5 (May 2020): 1507–13. http://dx.doi.org/10.1161/strokeaha.119.028143.
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Background and Purpose— We examined if ischemic stroke is associated with white matter degeneration predominantly confined to the ipsi-lesional tracts or with widespread bilateral axonal loss independent of lesion laterality. Methods— We applied a novel fixel-based analysis, sensitive to fiber tract–specific differences within a voxel, to assess axonal loss in stroke (N=104, 32 women) compared to control participants (N=40, 15 women) across the whole brain. We studied microstructural differences in fiber density and macrostructural (morphological) changes in fiber cross-section. Results— In participants with stroke, we observed significantly lower fiber density and cross-section in areas adjacent, or connected, to the lesions (eg, ipsi-lesional corticospinal tract). In addition, the changes extended beyond directly connected tracts, independent of the lesion laterality (eg, corpus callosum, bilateral inferior fronto-occipital fasciculus, right superior longitudinal fasciculus). Conclusions— We conclude that ischemic stroke is associated with extensive neurodegeneration that significantly affects white matter integrity across the whole brain. These findings expand our understanding of the mechanisms of brain volume loss and delayed cognitive decline in stroke.
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Pathmanandavel, Sarennya, Megan Crumbaker, Andrew O. Yam, Andrew Nguyen, Remy Niman, Peter Wilson, Shikha Sharma, et al. "Quantifying molecular imaging patterns of treatment response or progression using a novel traffic light workflow within a prospective phase I/II trial of 177LuPSMA-617 and NOX66 (LuPIN)." Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022): 166. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.166.
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166 Background: 177Lutetium PSMA-617 (LuPSMA) is an effective therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance may occur. We developed a quantitative workflow for serial PSMA PET/CT to optimise predictive and prognostic imaging biomarker capability for progression free (PFS) and overall survival (OS). Methods: 56 men with mCRPC previously treated with taxane chemotherapy and androgen signaling inhibitor were enrolled, receiving up to 6 doses of LuPSMA and a radiation sensitizer idronoxil (NOX66). 68Ga-PSMA-11 PET/CT was performed at study entry and exit. Traffic Light (TL) quantification workflow was developed to track changes in both tumour volume and intensity at a total body and lesional level. Lesions were classified as responding in green (>30% decline in volume), stable in yellow (<30% change in volume/intensity), progressive in red (>30% increase in volume/intensity, or new). Overall response pattern was categorised as responding ( green/yellow), low volume red (<50% progressive disease) or high volume red (>50% progressive disease). TL workflow results were correlated with PFS and OS. Results: 37/56 men underwent both entry and exit imaging. The median PSA decline was 77% (IQR 34-92%), and 70% (26/37) achieved PSA response >50%. PSA progression occurred in 54% (20/37) at exit imaging. Median PFS was 8.6 months (95%CI 5.6-11.6) and median OS 22 months (95% CI 18.6-25.6). 95% (35/37) had reduction in PSMA SUVmax (-26.1 (IQR +11.7 to -89.4)) and SUVmean (-3.3 (+2.9 to -14.2)). PSMA total tumor volume reduced in 68% (25/37) (median -0.64 liters (range +1.44 to -1.1)). On TL workflow, 24% (9/37) had responding/stable disease ( green/ yellow), 76% (28/37) had progressive disease ( red) of whom 41% (15/37) had low volume progression and 35% (13/37) high volume progression. Men with high volume progression had worse OS compared to responders (HR 0.18 (0.05-0.59), p 0.005), and low volume progression (HR 0.30 (0.11-0.80), p 0.02). 68% (19/28) had progression on both TL workflow and PSA, while 32% (9/28) had progression on TL workflow without PSA progression. In multivariable analysis, TL workflow and PSA progression at time of exit scans were independent predictors of OS (Table). Conclusions: This study demonstrates the feasibility of characterizing lesional response on molecular imaging with a quantification TL workflow. TL workflow response independently correlated with survival outcomes, indicating serial PSMA PET has prognostic biomarker potential. Clinical trial information: ACTRN12618001073291.[Table: see text]
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Monteith, Stephen, John Snell, Mathew Eames, Neal F. Kassell, Edward Kelly, and Ryder Gwinn. "Transcranial magnetic resonance–guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study." Journal of Neurosurgery 125, no. 6 (December 2016): 1557–64. http://dx.doi.org/10.3171/2015.10.jns1542.
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OBJECTIVE In appropriate candidates, the treatment of medication-refractory mesial temporal lobe epilepsy (MTLE) is primarily surgical. Traditional anterior temporal lobectomy yields seizure-free rates of 60%–70% and possibly higher. The field of magnetic resonance–guided focused ultrasound (MRgFUS) is an evolving field in neurosurgery. There is potential to treat MTLE with MRgFUS; however, it has appeared that the temporal lobe structures were beyond the existing treatment envelope of currently available clinical systems. The purpose of this study was to determine whether lesional temperatures can be achieved in the target tissue and to assess potential safety concerns. METHODS Cadaveric skulls with tissue-mimicking gels were used as phantom targets. An ablative volume was then mapped out for a “virtual temporal lobectomy.” These data were then used to create a target volume on the InSightec ExAblate Neuro system. The target was the amygdala, uncus, anterior 20 mm of hippocampus, and adjacent parahippocampal gyrus. This volume was approximately 5cm3. Thermocouples were placed on critical skull base structures to monitor skull base heating. RESULTS Adequate focusing of the ultrasound energy was possible in the temporal lobe structures. Using clinically relevant ultrasound parameters (power 900 W, duration 10 sec, frequency 650 kHz), ablative temperatures were not achieved (maximum temperature 46.1°C). Increasing sonication duration to 30 sec demonstrated lesional temperatures in the mesial temporal lobe structures of interest (up to 60.5°C). Heating of the skull base of up to 24.7°C occurred with 30-sec sonications. CONCLUSIONS MRgFUS thermal ablation of the mesial temporal lobe structures relevant in temporal lobe epilepsy is feasible in a laboratory model. Longer sonications were required to achieve temperatures that would create permanent lesions in brain tissue. Heating of the skull base occurred with longer sonications. Blocking algorithms would be required to restrict ultrasound beams causing skull base heating. In the future, MRgFUS may present a minimally invasive, non-ionizing treatment of MTLE.
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Webb, Philip, Mark Zorman, Rhona Watson, Gemma Austin, Carol Thurgood, Nick Coupe, Miranda Payne, and Claire Hobbs. "Stereotactic radiosurgery combined with immune checkpoint inhibition for the treatment of melanoma brain metastases is associated with high levels of extracranial disease control and survivorship - an abscopal effect?" Neuro-Oncology 23, Supplement_4 (October 1, 2021): iv16. http://dx.doi.org/10.1093/neuonc/noab195.040.
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Abstract Aims Melanoma brain metastases (MBM) are a common presentation to the neuro-oncology MDT. Stereotactic radiosurgery (SRS) is a highly effective treatment for cerebral metastases, with at least 70% control rates of individual metastases,[1] whilst immune checkpoint blockade has revolutionised the management of metastatic melanoma in recent years.[2] Recent studies have demonstrated that immune checkpoint inhibition alone also has activity in the brain, with MBM response rates of 50% or more.[3, 4] When MBM are treated with combination immunotherapy and SRS together, 12-month intracranial progression free survival (PFS) rates of 85% have been achieved.[4, 5] The aim of the current study was to evaluate the local control of MBM treated at our tertiary referral centre, which benefits from specialist neuro-radiology peer review of SRS contour volumes, and further to investigate whether overall survival is also improved, and what the mechanism of this may be. Method A retrospective analysis of all patients treated with SRS for brain metastases at our teriary SRS centre between June 2017 – January 2020 was performed. Inclusion criteria included patients treated for MBM, who received at least 2 doses of any combination of immune checkpoint inhibition concurrently with (defined as at the time of or commenced within 3 months of) SRS. The primary endpoints were the intracranial and extracranial response rates and survival rate at 12 months. Response was defined as complete response, partial response or stable disease. Secondary endpoints included the rate of imaging-defined radionecrosis, median lesional progression free survival (mPFSlesion), non-lesional intracranial PFS (mPFSintracranial), extracranial PFS (mPFSextracranial) and overall survival (mOS), measured from the start date of SRS to the date of event or censored at the start date of data collection. Kaplan-Meier curves and survival statistics were generated using SPSS v26. Results 33 MBM from 18 patients were identified. The median follow up was 25.8 months (minimum 12 months). Of the 18 patients: the median age was 60 (IQR 48 – 72); 17 (94%) patients were ECOG performance status 0-1; the median number of extracranial disease sites was 2 (pre-immunotherapy) and 1 (pre-SRS); the median duration of immunotherapy treatment was 17.6 (12.9 – 28.5) months, and the median number of metastases treated per patient was 2. Of the 33 metastases: 31 (94%) were supratentorial; 6 (18%) underwent prior neurosurgical resection; the median GTV volume (cc) of unresected metastases was 0.5cc (0.1 – 2.7), and 21 (64%) were treated with single fraction SRS. The median OS and PFS for all subtypes were not reached. The rates of OS, PFSlesion, PFSintracranial and PFSextracranial at 12 months were 93.9%, 87.9%, 81.8% & 75.8% respectively. Conclusion Our cohort of MBM patients appear to perform favourably when compared with the current literature. When compared to a recent extensive systematic review of modern management of MBM, our lesional control rate is as good as the weighted average of concurrent SRS + immunotherapy studies (87.9% vs 85.4% 12-month PFS), however we demonstrate a significantly improved 12-month OS rate (93.9% vs 52.8%) compared to the same (mOS of 15.8 – 17.4 months in other studies).[6,7] Our extra-lesional PFS is high and, compared to extracranial PFS rates from 51% at 6-months to 70.4% at 9-months in the literature,[3,4] our 75.8% control at 12 months suggests that extracranial control could drive the OS benefit. This suggests a benefit of SRS beyond the local control of MBM and questions whether patients without brain metastases may benefit from body SABR to extracranial metastases, to elicit a similar, potentially abscopal type effect.
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Deppe, Michael, Karsten Tabelow, Julia Krämer, Jan-Gerd Tenberge, Patrick Schiffler, Stefan Bittner, Wolfram Schwindt, Frauke Zipp, Heinz Wiendl, and Sven G. Meuth. "Evidence for early, non-lesional cerebellar damage in patients with multiple sclerosis: DTI measures correlate with disability, atrophy, and disease duration." Multiple Sclerosis Journal 22, no. 1 (April 28, 2015): 73–84. http://dx.doi.org/10.1177/1352458515579439.
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Background: Common symptoms of multiple sclerosis (MS) such as gait ataxia, poor coordination of the hands, and intention tremor are usually the result of dysfunctionality in the cerebellum. Magnetic resonance imaging (MRI) has frequently failed to detect cerebellar damage in the form of inflammatory lesions in patients presenting with symptoms of cerebellar dysfunction. Objective: To detect microstructural cerebellar tissue alterations in early MS patients with a “normal appearing” cerebellum using diffusion tensor imaging (DTI). Methods: A total of 68 patients with relapsing–remitting MS (RRMS) and without cerebellar lesions and 26 age-matched healthy controls were admitted to high-resolution MRI and DTI to assess microstructure and volume of the cerebellar white matter (CBWM). Results: We found cerebellar fractional anisotropy (FA) and CBWM volume reductions in the group of 68 patients. Interestingly, a subgroup of these patients that was derived by including only patients with early and mild MS ( N=23, median age 30 years, median Expanded Disability Status Scale =1.5, median duration 28 months) showed already cerebellar FA but no CBWM volume reductions. FA reductions were correlated with disability, atrophy, and disease duration. Conclusion: “Normal appearing” cerebellar white matter can be damaged in a very early stage of RRMS. DTI seems to be a sensitive tool for detecting this hidden cerebellar damage.
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Ma, Ashley Y., Rita C. Vitorino, Seyed-Parsa Hojjat, Alannah D. Mulholland, Liying Zhang, Liesly Lee, Timothy J. Carroll, Charles G. Cantrell, Chase R. Figley, and Richard I. Aviv. "The relationship between white matter fiber damage and gray matter perfusion in large-scale functionally defined networks in multiple sclerosis." Multiple Sclerosis Journal 23, no. 14 (February 9, 2017): 1884–92. http://dx.doi.org/10.1177/1352458517691149.
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Background: Recent studies utilizing perfusion as a surrogate of cortical integrity show promise for overall cognition, but the association between white matter (WM) damage and gray matter (GM) integrity in specific functional networks is not previously studied. Objective: To investigate the relationship between WM fiber integrity and GM node perfusion within six functional networks of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients. Methods: Magnetic resonance imaging (MRI) and neurocognitive testing were performed on 19 healthy controls (HC), 39 RRMS, and 45 SPMS patients. WM damage extent and severity were quantified with T2-hyper/T1-hypointense (T2h/T1h) lesion volume and degree of perfusion reduction in lesional and normal-appearing white matter (NAWM), respectively. A two-step linear regression corrected for confounders was employed. Results: Cognitive impairment was present in 20/39 (51%) RRMS and 25/45 (53%) SPMS patients. GM node perfusion was associated with WM fiber damage severity (WM hypoperfusion) within each network—including both NAWM ( R2 = 0.67–0.89, p < 0.0001) and T2h ( R2 = 0.39–0.62, p < 0.0001) WM regions—but was not significantly associated ( p > 0.01) with WM fiber damage extent (i.e. T2h/T1h lesion volumes). Conclusion: Overall, GM node perfusion was associated with severity rather than extent of WM network damage, supporting a primary etiology of GM hypoperfusion.
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Feng, Jenny, Erik Offerman, Jian Lin, Elizabeth Fisher, Sarah M. Planchon, Ken Sakaie, Mark Lowe, Kunio Nakamura, Jeffrey A. Cohen, and Daniel Ontaneda. "Exploratory MRI measures after intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis." Multiple Sclerosis Journal - Experimental, Translational and Clinical 5, no. 2 (April 2019): 205521731985603. http://dx.doi.org/10.1177/2055217319856035.
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Background Mesenchymal stem cells (MSC) have immunomodulatory and neuro-protective properties and are being studied for treatment of multiple sclerosis (MS). Tractography-based diffusion tensor imaging (DTI), cortical thickness (Cth) and T2 lesion volume (T2LV) can provide insight into treatment effects. Objective The objective of this study was to analyse the effects of MSC transplantation in MS on exploratory MRI measures. Methods MRIs were obtained from 24 MS patients from a phase 1 open-label study of autologous MSC transplantation. DTI metrics were obtained in lesions and normal-appearing white matter motor tracts (NAWM). T2LV and Cth were derived. Longitudinal evolution of MRI outcomes were modelled using linear mixed effects. Pearson’s correlation was calculated between MRI and clinical measures. Results Lesional radial diffusivity (RD) and axial diffusivity (AD) decreased pre-transplant and showed no changes post-transplant. There were mixed trends in NAWM RD and AD pre/post-transplant. Transplantation stabilized T2LV growth. NAWM RD and AD correlated with Cth, T2LV and with leg and arm function but not with cognition. Lesional DTI demonstrated similar but less robust correlations. Conclusions Microstructural tissue integrity is altered in MS. DTI changes pre-transplant may be influenced by concomitant lesion accrual. Contributor to DTI stabilization post-transplant is multifactorial. DTI of major motor tracts correlated well with clinical measures, highlighting its sensitivity to clinically meaningful changes.
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Harrison, Daniel M., Jiwon Oh, Snehashis Roy, Emily T. Wood, Anna Whetstone, Michaela A. Seigo, Craig K. Jones, et al. "Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and relationship to cortical pathology." Multiple Sclerosis Journal 21, no. 9 (January 12, 2015): 1139–50. http://dx.doi.org/10.1177/1352458514558134.
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Objective: Pathology in both cortex and deep gray matter contribute to disability in multiple sclerosis (MS). We used the increased signal-to-noise ratio of 7-tesla (7T) MRI to visualize small lesions within the thalamus and to relate this to clinical information and cortical lesions. Methods: We obtained 7T MRI scans on 34 MS cases and 15 healthy volunteers. Thalamic lesion number and volume were related to demographic data, clinical disability measures, and lesions in cortical gray matter. Results: Thalamic lesions were found in 24/34 of MS cases. Two lesion subtypes were noted: discrete, ovoid lesions, and more diffuse lesional areas lining the periventricular surface. The number of thalamic lesions was greater in progressive MS compared to relapsing–remitting (mean ±SD, 10.7 ±0.7 vs. 3.0 ±0.7, respectively, p < 0.001). Thalamic lesion burden (count and volume) correlated with EDSS score and measures of cortical lesion burden, but not with white matter lesion burden or white matter volume. Conclusions: Using 7T MRI allows identification of thalamic lesions in MS, which are associated with disability, progressive disease, and cortical lesions. Thalamic lesion analysis may be a simpler, more rapid estimate of overall gray matter lesion burden in MS.
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Bagnato, Francesca, Giulia Franco, Fei Ye, Run Fan, Patricia Commiskey, Seth A. Smith, Junzhong Xu, and Richard Dortch. "Selective inversion recovery quantitative magnetization transfer imaging: Toward a 3 T clinical application in multiple sclerosis." Multiple Sclerosis Journal 26, no. 4 (March 25, 2019): 457–67. http://dx.doi.org/10.1177/1352458519833018.
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Background:Assessing the degree of myelin injury in patients with multiple sclerosis (MS) is challenging due to the lack of magnetic resonance imaging (MRI) methods specific to myelin quantity. By measuring distinct tissue parameters from a two-pool model of the magnetization transfer (MT) effect, quantitative magnetization transfer (qMT) may yield these indices. However, due to long scan times, qMT has not been translated clinically.Objectives:We aim to assess the clinical feasibility of a recently optimized selective inversion recovery (SIR) qMT and to test the hypothesis that SIR-qMT-derived metrics are informative of radiological and clinical disease-related changes in MS.Methods:A total of 18 MS patients and 9 age- and sex-matched healthy controls (HCs) underwent a 3.0 Tesla (3 T) brain MRI, including clinical scans and an optimized SIR-qMT protocol. Four subjects were re-scanned at a 2-week interval to determine inter-scan variability.Results:SIR-qMT measures differed between lesional and non-lesional tissue ( p < 0.0001) and between normal-appearing white matter (NAWM) of patients with more advanced disability and normal white matter (WM) of HCs ( p < 0.05). SIR-qMT measures were associated with lesion volumes, disease duration, and disability scores ( p ⩽ 0.002).Conclusion:SIR-qMT at 3 T is clinically feasible and predicts both radiological and clinical disease severity in MS.
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Cacciaguerra, Laura, Elisabetta Pagani, Sharlota Mesaros, Jelena Dackovic, Irena Dujmovic-Basuroski, Jelena Drulovic, Paola Valsasina, Massimo Filippi, and Maria Assunta Rocca. "Dynamic volumetric changes of hippocampal subfields in clinically isolated syndrome patients: A 2-year MRI study." Multiple Sclerosis Journal 25, no. 9 (July 24, 2018): 1232–42. http://dx.doi.org/10.1177/1352458518787347.
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Background:Different subregional patterns of hippocampal involvement have been observed in diverse multiple sclerosis (MS) phenotypes.Objective:To evaluate the occurrence of regional hippocampal variations in clinically isolated syndrome (CIS) patients, their relationships with focal white matter (WM) lesions, and their prognostic implications.Methods:Brain dual-echo and three-dimensional (3D) T1-weighted scans were acquired from 14 healthy controls and 36 CIS patients within 2 months from clinical onset and after 3, 12, and 24 months. Radial distance distribution was assessed using 3D parametric surface mesh models. A cognitive screening was also performed.Results:Patients showed clusters of reduced radial distance in the Cornu Ammonis 1 from month 3, progressively extending to the subiculum, negatively correlated with ipsilateral T2 and T1 lesion volume. Increased radial distance appeared in the right dentate gyrus after 3 ( p < 0.05), 12, and 24 ( p < 0.001) months, and in the left one after 3 and 24 months ( p < 0.001), positively correlated with lesional measures. Hippocampal volume variations were more pronounced in patients converting to MS after 24 months and did not correlate with cognitive performance.Conclusion:Regional hippocampal changes occur in CIS, are more pronounced in patients converting to MS, and are modulated by focal WM lesions.
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Beek, Johan, Nicanor Moldovan, Chantal van der Horst, Martin van Gemert, and Michal Heger. "Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains." Thrombosis and Haemostasis 93, no. 02 (2005): 242–56. http://dx.doi.org/10.1160/th04-05-0291.
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SummaryFor the past two decades much research on selective photothermolysis of port wine stain vasculature has been devoted to optimizing laser parameters. Unfortunately, 60% of patients still respond suboptimally to laser therapy, despite significant innovations in treatment strategies and laser technology. Here we present a novel treatment approach based on combining selective photothermolysis with the administration of prothrombotic and/or anti-fibrinolytic pharmaceutical agents, with the aim of enhancing vaso-occlusion and post-treatment remodelling in difficult-to-target vessels. A hypercoagulable state of blood will instill laser-induced occlusive thrombosis in a wider array of vessel diameters at greater dermal depths, whereby larger vascular segments will ultimately undergo the chronic inflammatory processes that result in blood volume reduction, and thus lesional blanching. With thrombosis as a primary trigger for these inflammatory processes, we have extrapolated the thresh-old damage profile that is required for clinically relevant thrombus formation. Consequently, a recently proposed model of thrombus organization, in which recanalization is associated with endothelial progenitor cell-mediated neovasculogenesis, is elaborated in the framework of lesional blanching and juxtaposed to angiogenic reconstruction of affected dermal vasculature. Since neovasculogenesis and angiogenesis are regulated by the degree of vaso-occlusion and corollary drop in local oxygen tension, both can be manipulated by the administration of procoagulant pharmaceuticals. Lastly, in an effort to optimally balance selective photothermolysis with pharmacokinetics and clinical safety, the use of a gold nanoshell drug delivery system, in which the procoagulant drugs are encapsulated by a wavelength-modulated, gold-coated polymer matrix, is proposed. We have termed this modality site-specific pharmaco-laser therapy.
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Tran, S., A. Thomas, M. Touat, C. Karachi, F. Lozano, K. Mokhtari, C. Dehais, et al. "OS07.1.A A threshold of mitotic activity and post-surgery residual volume are independant prognostic factors in astrocytoma IDH-mutant." Neuro-Oncology 24, Supplement_2 (September 1, 2022): ii15. http://dx.doi.org/10.1093/neuonc/noac174.046.
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Abstract Background The distinction between grade 2 and 3 is instrumental to choose between observational follow-up and adjuvant treatment in resected astrocytoma IDH-mutant. However, criteria of grade 2 versus 3 have not been updated since the WHO 2007 classification. There is no consensus on the method of evaluation of the mitotic activity or a cut-off of mitoses separating grade 2 and grade 3 tumors. The objectives were to evaluate the maximal mitotic activity on a series of resected astrocytoma IDH-mutant and assess its prognostic impact on survival. Material and Methods Maximal mitotic activity on consecutive high power fields corresponding to 3 mm2 was examined in 118 lower-grade astrocytoma IDH-mutant. The prognostic value for time-to-treatment (TTT) and overall survival (OS) of mitotic activity and other putative prognostic factors (including age, performance status, pre-surgical tumor volume, plurilobar involvement, post-surgical residual tumor volume, midline involvement) was assessed in tumors with (i) ATRX loss, and (ii) without CDKN2A homozygous deletion, lesional enhancement, histological necrosis nor microvascular proliferation. Results Among the 75 (64%) of tumors which had gone through observational follow-up after resection, the maximal mitotic activity, the post-surgical residual volume and the plurilobar involvement were independent prognostic factors of TTT (p < 0.0001). A threshold of mitotic activity for grade 2 was fitted on TTT and OS prognosis. Using this threshold, patients with “grade 2 tumors” had a median TTT of 55 months versus 19 months for “grade 3” (p = 0.0057) and a median OS of 102 months versus 73 months respectively (p = 0.001). Residual volume < 1 cm3 was associated with longer OS (113 months versus 88 months, p = 0.0021). Conclusion Mitotic activity and post-surgical residual volume can be combined to evaluate prognosis in resected astrocytoma IDH-mutant and could select the best candidates for observational follow-up.
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Tran, Suzanne, Alice Thomas, Mehdi Touat, Carine Karachi, Caroline Dehais, Loïc Feuvret, Karima Mokhtari, et al. "PATH-16. THRESHOLDS OF MITOTIC ACTIVITY AND POST-SURGERY RESIDUAL VOLUME ARE INDEPENDENT PROGNOSTIC FACTORS IN ASTROCYTOMA IDH-MUTANT." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii153. http://dx.doi.org/10.1093/neuonc/noac209.589.
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Abstract BACKGROUND The distinction between grade 2 and 3 is instrumental to choose between observational follow-up and adjuvant treatment in resected astrocytoma IDH-mutant. However, criteria for discriminating grade 2 and 3 tumors have not been updated since the WHO 2007 classification. There is no consensus on the method of evaluation of the mitotic activity or a mitosis cut-off for grading. The objectives were to evaluate the maximal mitotic activity on a series of resected astrocytoma IDH-mutant and assess its prognostic impact on survival. METHODS Maximal mitotic activity on consecutive high-power fields corresponding to 3 mm2 was examined in 118 lower-grade astrocytomas IDH-mutant. The prognostic value for time-to-treatment (TTT) and overall survival (OS) of mitotic activity as well as other prognostic factors (including age, performance status, presurgical tumor volume, plurilobar involvement, postsurgical residual tumor volume, midline involvement) was assessed in tumors with (i) ATRX loss, and (ii) without CDKN2A homozygous deletion, lesional enhancement, histological necrosis nor microvascular proliferation. RESULTS Among the 75 (64%) tumors which had gone through observational follow-up after resection, maximal mitotic activity, post-surgical residual volume and plurilobar involvement were independent prognostic factors of TTT (p < 0.0001). A threshold of mitotic activity for grade 2 was fitted using TTT and OS parameters. Using this threshold, patients with “grade 2 tumors” had a median TTT of 55 months versus 19 months for “grade 3” (p= 0.0057) and a median OS of 102 months versus 73 months respectively (p= 0.001). Residual volume < 1 cm3 was associated with longer OS (113 months versus 88 months, p= 0.0021). CONCLUSIONS The combination of mitotic activity and postsurgical residual volume improves prognostication in resected astrocytoma IDH-mutant. This novel risk assessment method could identify the best candidates for observational follow-up.
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Ozturk, A., SA Smith, EM Gordon-Lipkin, DM Harrison, N. Shiee, DL Pham, BS Caffo, PA Calabresi, and DS Reich. "MRI of the corpus callosum in multiple sclerosis: association with disability." Multiple Sclerosis Journal 16, no. 2 (February 2010): 166–77. http://dx.doi.org/10.1177/1352458509353649.
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Inflammatory demyelination and axon damage in the corpus callosum are prominent features of multiple sclerosis (MS) and may partially account for impaired performance on complex tasks. The objective of this article was to characterize quantitative callosal MRI abnormalities and their association with disability. In 69 participants with MS and 29 healthy volunteers, lesional and extralesional callosal MRI indices were estimated via diffusion tensor tractography. expanded disability status scale (EDSS) and MS functional composite (MSFC) scores were recorded in 53 of the participants with MS. All tested callosal MRI indices were diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51). Scores on the overall MSFC and its paced serial auditory addition test (PASAT) and 9-hole peg test components were correlated with callosal fractional anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity (r = —0.29, —0.30, and —0.31) but not with overall callosal volume or callosal lesion volume; the PASAT score was more weakly correlated with callosal magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were associated with impaired PASAT performance and posterior abnormalities with slow performance on the 9-hole peg test. In conclusion, abnormalities in the corpus callosum can be assessed with quantitative MRI and are associated with cognitive and complex upper-extremity dysfunction in MS.
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Rojas, J. I., L. Patrucco, C. Besada, J. Funes, and E. Cristiano. "Diferencias en la tasa de atrofia global y regional y del volumen lesional entre género en esclerosis múltiple." Neurología 28, no. 7 (September 2013): 389–93. http://dx.doi.org/10.1016/j.nrl.2012.10.008.
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Marasescu, R., M. Cerezo Garcia, and Y. Aladro Benito. "Afectación visuoespacial/visuoconstrucción en pacientes con esclerosis múltiple. Relación con el volumen lesional regional y la atrofia subcortical." Neurología 31, no. 3 (April 2016): 169–75. http://dx.doi.org/10.1016/j.nrl.2015.06.003.
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Grgic, Aleksandar, Ursula Nestle, Elena Ballek, Klemens Scheidhauer, Cornelia Puskas, Jochem Koenig, Karin Hohloch, Joerg Schubert, Lorenz H. Truemper, and Carl-Martin Kirsch. "MERIT Study – “Multicenter Evaluation of Patient- and Lesion-Specific Prognostic Factors for RadioImmunoTherapy with 90yttrium-Labeled Anti-CD20 in Follicular Non-Hodgkin's lymphoma”." Blood 114, no. 22 (November 20, 2009): 4792. http://dx.doi.org/10.1182/blood.v114.22.4792.4792.
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Abstract Abstract 4792 Background / Aim Although prognostic factors (PF) for conventional lymphoma therapy are well known and used in clinical practice and medical research, the PF for radioimmunotherapy (RIT) have not been fully defined until now. The aim of this prospective multicenter trial is to identify patient- and lesion-specific PF for a standard RIT using 90Yttrium-labeled anti-CD20-antibodies in relapsed or refractory follicular lymphoma (FL) by means of clinical and image data including FDG-PET and CT. To prove the feasibility of the multicenter web-based data collection and to assess the imaging data we performed an analysis on retrospective data. Material and methods This retrospective analysis included clinical and image data of patients with FL from 3 German centers (UKS Homburg, TU Munich, SK Karlsruhe). Clinical data were documented using the ”International Registry on Radioimmunotherapy“ (RIT-Registry). PET and CT data were uploaded in pseudonymous form into an online archive designed for the purpose of this study (Hermes Medical Solutions®). Treatment response was evaluated both on patient and lesion basis. To do so, clinical parameters as well as the documented patient and image data were analysed for every measurable lesion in terms of location, standardized uptake value and volume. PF were evaluated using a uni- and multivariate generalized mixed linear model (MGMLM). Results Web-based data capture comprised a total of 32 patients (aged 44 up to 86 years) documented retrospectively in the RIT-Registry. From this group, 16 patients with at least 1 PET examination before and after RIT were further analysed. Altogether, 159 lesions were measured corresponding to 1 up to 25 lesions per patient. In regard to the patients response, 5/16 patients achieved a CR, 8/16 patients a PR and 3/16 patients remained with NC. 6 patients showed divergent findings (21/159 lesions). In the MGMLM evaluation, the number of lesions per patient (p=0.009), the maximum lesion volume (p=0.004), total volume of lesions per patient (p=0.001) and the FLIPI (p=0.01) were identified as prognostic factors for patient's response (CR, PR). Concerning the lesional response (CR, PR), initial small lesion volume (in PET and CT) and high metabolic activity (PET) were identified as prognostically relevant variables (both p=0.04). Only the maximum SUV (p<0.0001) in the preRIT scan showed a significant impact on lesional and patients CR. The data of 15 patients concerning the prospective study so far are currently being evaluated and will be presented during the meeting. Conclusion The web-based multicenter acquisition of patient and image data is technically feasible and allows a central evaluation. Based on the findings from the retrospective pilot study, the analysis of the ongoing prospective study will allow to the patient- and even lesion-specific PF for RIT in FL. The data of already available patients from the prospective study will also be presented during the meeting. Disclosures: No relevant conflicts of interest to declare.
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Baptista, Simone Conceição Oliveira. "Uso de cobertura com tecnologia hydrofiber a base de carboximetilcelulose sódica e prata iônica no tratamento da síndrome de Fournier infectada." Enfermagem Brasil 18, no. 3 (July 16, 2019): 437. http://dx.doi.org/10.33233/eb.v18i3.2529.
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Introdução: A Síndrome de Fournier (SF) é uma fasciíte necrosante polimicrobial que envolve o períneo e/ou genitália externa com sinergismo para parede abdominal, que tem origem no escroto podendo ficar confinada apenas nesta área e evoluir para o pênis, podendo acometer, raramente, as mulheres e as crianças. Objetivo: Relatar o caso de uma paciente portadora de SF que foi submetida ao desbridamento cirúrgico e teve como conduta terapêutica das lesões a utilização da carboximetilcelulose sódica e prata iônica (HCSPI). Metodologia: Trata-se de um estudo descritivo, do tipo relato de caso realizado na UTI Geral do Hospital Geral Roberto Santos em Salvador/BA no período de 25/04/17 a 10/05/2017. Para a coleta dos dados, utilizaram-se as anotações da equipe de enfermagem do prontuário da paciente, além dos critérios de avaliação diária da pele lesionada e o acompanhamento fotográfico. Resultados: O presente estudo demonstrou através do relato de caso, que o uso da cobertura primária com HCSPI influenciou diretamente na melhoria do volume da exsudação, na modificação do odor, no aspecto do centro da lesão e na regressão da extensa área lesionada. Conclusão: Relatou-se que a utilização da HCSPI na lesão infectada provocada pela SF, teve como resultado uma evolução satisfatória da lesão e no bem-estar físico, psicológico, social e emocional do paciente.Palavras-chave: gangrena de Fournier, cuidados de enfermagem, ferimentos e lesões, desbridamento, procedimentos cirúrgicos reconstrutivos.
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Göttler, Jens, Mathias Lukas, Anne Kluge, Stephan Kaczmarz, Jens Gempt, Florian Ringel, Mona Mustafa, et al. "Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma." European Journal of Nuclear Medicine and Molecular Imaging 44, no. 3 (December 2, 2016): 392–97. http://dx.doi.org/10.1007/s00259-016-3585-0.
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Murillo, V., P. Manonelles, A. García, and J. Álvarez. "Medidas de prevención de lesiones de futsal. Una comparación entre dos temporadas." Revista Internacional de Medicina y Ciencias de la Actividad Física y del Deporte 22, no. 85 (March 16, 2022): 47–58. http://dx.doi.org/10.15366/rimcafd2022.85.004.
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Diferentes estudios evidencian que la carga de entrenamiento es una causa importante en la afectación de lesiones deportivas y han identificado variables como el volumen y la intensidad del entrenamiento claves para la prevención de lesiones. El objetivo de este estudio es reducir la incidencia de lesiones implementando seis medidas preventivas. El estudio incluyó 12 jugadores del primer equipo de "Sala 10 Zaragoza" de la Primera División de la Liga de Futsal de España. Se trata de un estudio longitudinal comparativo de la incidencia de lesiones en la temporada 2016-2017 y la temporada 2004-2005. Los resultados obtenidos revelan un total de 28 y 108 lesiones registradas y una incidencia lesional de 6,86 y 19,72 durante la temporada 2016-2017 y la temporada 2004-2005, respectivamente. El número de minutos de partido perdidos fue mucho más bajo en la temporada 2016-2017, en comparación con la temporada 2004-2005, 6.660 frente a 31.500 minutos.
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Nestle, U., K. Scheidhauer, C. Puskas, E. Ballek, K. Hohloch, J. Schubert, J. König, et al. "Retrospective web-based multicenter evaluation of 18F-FDG-PET and CT derived predictive factors." Nuklearmedizin 50, no. 01 (2011): 39–47. http://dx.doi.org/10.3413/nukmed-0322-10-06.
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Summary Aim: Although predictive factors (PF) for conventional lymphoma therapy are established and frequently used in clinical practice and medical research, the PF for radioimmunotherapy (RIT) have not been fully defined until now. The aim of this multicenter evaluation is to prove the feasibility of the multicenter web-based data collection and to preliminary explore imaging findings and prediction of therapy response in patients with follicular lymphoma (FL) following radioimmuno therapy (RIT) with 90Y-ibritumomab tiuxetan. Patients, methods: We retrospectively analyzed and correlated clinical and imaging data (CT and FDG-PET) before and after RIT as documented by the RIT-Network. Evaluation of treatment response was done on both patient and lesion basis. Every measurable lesion was analyzed in terms of standardized uptake value (SUV), volume (CT and PET) and response. PF were identified using a uni- and multivariate model. A web-based system was used for the documentation and evaluation of clinical and imaging data. Results: 16 patients with at least one PET before and after RIT were eligible for analysis. Concerning response three months postRIT, 5 patients achieved a CR, 6 patients a PR and 4 patients remained with NC. A total of 159 lesions were measured (mean 10 ± 8). In the multivariate model the log lesion volume (p < 0.0001), the total (p = 0.03) and maximum lesion volume (p = 0.05) were predictors for response (CR + PR). Concerning the lesional CR initial small lesion volume (p = 0.009) and its high metabolic activity (p = 0.01) were identified as predictors. The web-based system showed no major disturbances allowing secure data transfer and central image interpretation in a reasonable time. Conclusion: The use of a web-based multicenter archiving system for clinical and imaging data is technically feasible in a multicenter setting and allows a central analysis. This preliminary analysis suggests that FDG-PET may predict the likelihood of response to RIT.
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Martins, Nuno, Ana Aires, Beatriz Mendez, Sandra Boned, Marta Rubiera, Alejandro Tomasello, Pilar Coscojuela, et al. "Ghost Infarct Core and Admission Computed Tomography Perfusion: Redefining the Role of Neuroimaging in Acute Ischemic Stroke." Interventional Neurology 7, no. 6 (2018): 513–21. http://dx.doi.org/10.1159/000490117.
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Background: Determining the size of infarct extent is crucial to elect patients for reperfusion therapies. Computed tomography perfusion (CTP) based on cerebral blood volume may overestimate infarct core on admission and consequently include ghost infarct core (GIC) in a definitive lesional area. Purpose: Our goal was to confirm and better characterize the GIC phenomenon using CTP cerebral blood flow (CBF) as the reference parameter to determine infarct core. Methods: We performed a retrospective, single-center analysis of consecutive thrombectomies of middle cerebral or intracranial internal carotid artery occlusions considering noncontrast CT Alberta Stroke Program Early CT Score ≥6 in patients with pretreatment CTP. We used the RAPID® software to measure admission infarct core based on initial CBF. The final infarct was extracted from follow-up CT. GIC was defined as initial core minus final infarct > 10 mL. Results: A total of 123 patients were included. The median National Institutes of Health Stroke Scale score was 18 (13–20), the median time from symptoms to CTP was 188 (67–288) min, and the recanalization rate (Thrombolysis in Cerebral Infarction score 2b, 2c, or 3) was 83%. Twenty patients (16%) presented with GIC. GIC was associated with shorter time to recanalization (150 [105–291] vs. 255 [163–367] min, p = 0.05) and larger initial CBF core volume (38 [26–59] vs. 6 [0–27] mL, p < 0.001). An adjusted logistic regression model identified time to recanalization < 302 min (OR 4.598, 95% CI 1.143–18.495, p = 0.032) and initial infarct volume (OR 1.01, 95% CI 1.001–1.019, p = 0.032) as independent predictors of GIC. At 24 h, clinical improvement was more frequent in patients with GIC (80 vs. 49%, p = 0.01). Conclusions: CTP CBF < 30% may overestimate infarct core volume, especially in patients imaged in the very early time window and with fast complete reperfusion. Therefore, the CTP CBF technique may exclude patients who would benefit from endovascular treatment.
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Nascimento, Jackeline Matos, Walber Luiz Gavassoni, Lilian Maria Arruda Bacchi, Bruno Zuntini, Evandro Puhl Melo, and Renan Kobayashi Leonel. "Número de aplicações e uso de adjuvantes, adicionados à fungicidas no controle da ferrugem asiática da soja." Agrarian 11, no. 40 (May 28, 2018): 95–104. http://dx.doi.org/10.30612/agrarian.v11i40.4210.
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O uso de aditivos na calda dos fungicidas é recomendado pelos fabricantes, porém, o efeito de diferentes associações fungicida x adjuvantes é pouco conhecida. Foram realizados experimentos nas safras 2009/2010 e 2010/2011, com o objetivo de avaliar o efeito da adição de adjuvantes de diferentes naturezas químicas, sendo eles óleos mineral, óleo vegetal, e adjuvantes siliconados adicionados aos fungicidas picoxistrobina + ciproconazol, todos com uma e duas aplicações, totalizando doze tratamentos + testemunha (sem fungicida). Avaliou-se número de lesões, urédias, e porcentagem de área lesionada pela doença. Na safra 2010/2011, durante a segunda aplicação, foram utilizados papeis hidrossensíveis, avaliou-se diâmetro da mediana volumétrica (DMV), diâmetro da mediana numérica (DMN), coeficiente de variação de gotas (CV), densidade (número de gotas cm-²), volume recuperado (L ha-1) e área coberta pela calda fungicida (%). Nas duas safras, todos os adjuvantes associados ao fungicida proporcionaram redução na AACPD. Na Safra 2010/2011, os tratamentos com Silwet® e Nimbus®, em geral, resultou em maiores valores de DMV, CV, DMN, volume recuperado e porcentagem de área coberta. A adição de adjuvante siliconado, óleos minerais ou óleos vegetais ao fungicida são eficazes e não diferem do adjuvante Nimbus®, recomendado pelo fabricante dos fungicidas utilizados.
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Eijlers, Anand J. C., Iris Dekker, Martijn D. Steenwijk, Kim A. Meijer, Hanneke E. Hulst, Petra J. W. Pouwels, Bernard M. J. Uitdehaag, et al. "Cortical atrophy accelerates as cognitive decline worsens in multiple sclerosis." Neurology 93, no. 14 (September 4, 2019): e1348-e1359. http://dx.doi.org/10.1212/wnl.0000000000008198.
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ObjectiveTo determine which pathologic process could be responsible for the acceleration of cognitive decline during the course of multiple sclerosis (MS), using longitudinal structural MRI, which was related to cognitive decline in relapsing-remitting MS (RRMS) and progressive MS (PMS).MethodsA prospective cohort of 230 patients with MS (179 RRMS and 51 PMS) and 59 healthy controls was evaluated twice with 5-year (mean 4.9, SD 0.94) interval during which 22 patients with RRMS converted to PMS. Annual rates of cortical and deep gray matter atrophy as well as lesion volume increase were computed on longitudinal (3T) MRI data and correlated to the annual rate of cognitive decline as measured using an extensive cognitive evaluation at both time points.ResultsThe deep gray matter atrophy rate did not differ between PMS and RRMS (−0.82%/year vs −0.71%/year, p = 0.11), while faster cortical atrophy was observed in PMS (−0.87%/year vs −0.48%/year, p < 0.01). Similarly, faster cognitive decline was observed in PMS compared to RRMS (p < 0.01). Annual cognitive decline was related to the rate of annual lesion volume increase in stable RRMS (r = −0.17, p = 0.03) to the rate of annual deep gray matter atrophy in converting RRMS (r = 0.50, p = 0.02) and annual cortical atrophy in PMS (r = 0.35, p = 0.01).ConclusionsThese results indicate that cortical atrophy and cognitive decline accelerate together during the course of MS. Substrates of cognitive decline shifted from worsening lesional pathology in stable RRMS to deep gray matter atrophy in converting RRMS and to accelerated cortical atrophy in PMS only.
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Schettino, Maria Gabriella, Ornella Piazza, Carmine Vecchione, Maria Consiglio Calabrese, Antonella Maisto, and Vincenzo De Paola. "Riabilitazione polmonare precoce per polmonite SARS-CoV-2." La Sanità Pubblica. Ricerca applicata 2, no. 2 (July 25, 2021): 95–98. http://dx.doi.org/10.48268/covid/2021/0001.2.
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La ventilazione meccanica in posizione prona viene utilizzata per migliorare l’ossigenazione e mitigare gli effetti dannosi della ventilazione meccanica nei pazienti con sindrome da distress respiratorio acuto (ARDS). La sindrome da distress respiratorio acuto (ARDS) è una malattia fulminante caratterizzata da ridotta ossigenazione, congestione polmonare e ridotta compliance polmonare a seguito di un danno polmonare diretto, come aspirazione o polmonite, o una lesione sistemica, come sepsi o trauma. In molti pazienti con ARDS la ventilazione meccanica può danneggiare ulteriormente i polmoni, portando a morbilità e mortalità a lungo termine. Sebbene la riduzione al minimo dei volumi correnti e l’ottimizzazione della pressione positiva di fine espirazione (PEEP) possano ridurre il danno polmonare la mortalità associata all’ARDS rimane elevata.
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Patel, Sarvatit, Lauren Mastrogiacomo, Madison Fulmer, Yuanyuan Shi, and Geoff H. Werstuck. "Deletion of Macrophage-Specific Glycogen Synthase Kinase (GSK)-3α Promotes Atherosclerotic Regression in Ldlr−/− Mice." International Journal of Molecular Sciences 23, no. 16 (August 18, 2022): 9293. http://dx.doi.org/10.3390/ijms23169293.
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Recent evidence from our laboratory suggests that impeding ER stress–GSK3α/β signaling attenuates the progression and development of atherosclerosis in mouse model systems. The objective of this study was to determine if the tissue-specific genetic ablation of GSK3α/β could promote the regression of established atherosclerotic plaques. Five-week-old low-density lipoprotein receptor knockout (Ldlr−/−) mice were fed a high-fat diet for 16 weeks to promote atherosclerotic lesion formation. Mice were then injected with tamoxifen to induce macrophage-specific GSK3α/β deletion, and switched to standard diet for 12 weeks. All mice were sacrificed at 33 weeks of age and atherosclerosis was quantified and characterized. Female mice with induced macrophage-specific GSK3α deficiency, but not GSK3β deficiency, had reduced plaque volume (~25%) and necrosis (~40%) in the aortic sinus, compared to baseline mice. Atherosclerosis was also significantly reduced (~60%) in the descending aorta. Macrophage-specific GSK3α-deficient mice showed indications of increased plaque stability and reduced inflammation in plaques, as well as increased CCR7 and ABCA1 expression in lesional macrophages, consistent with regressive plaques. These results suggest that GSK3α ablation promotes atherosclerotic plaque regression and identify GSK3α as a potential target for the development of new therapies to treat existing atherosclerotic lesions in patients with cardiovascular disease.
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Liberato, Afonso P., Eric J. Mallack, Razina Aziz-Bose, Doug Hayden, Arne Lauer, Paul A. Caruso, Patricia L. Musolino, and Florian S. Eichler. "MRI brain lesions in asymptomatic boys with X-linked adrenoleukodystrophy." Neurology 92, no. 15 (March 22, 2019): e1698-e1708. http://dx.doi.org/10.1212/wnl.0000000000007294.
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ObjectiveTo describe the brain MRI findings in asymptomatic patients with childhood cerebral adrenoleukodystrophy (CCALD).MethodsWe retrospectively reviewed a series of biochemically or genetically confirmed cases of adrenoleukodystrophy followed at our institution between 2001 and 2015. We identified and analyzed 219 brain MRIs from 47 asymptomatic boys (median age 6.0 years). Patient age, MRI scan, and brain lesion characteristics (e.g., contrast enhancement, volume, and Loes score) were recorded. The rate of lesion growth was estimated using a linear mixed effect model.ResultsSixty percent of patients (28/47) showed brain lesions (median Loes score of 3.0 points; range 0.5–11). Seventy-nine percent of patients with CCALD (22/28) had contrast enhancement on first lesional or subsequent MRI. Lesion progression (Loes increase of ≥0.5 point) was seen in 50% of patients (14/28). The rate of lesion growth (mL/mo) was faster in younger patients (r = −0.745; p < 0.0001). Older patients (median age 14.4 y/o) tended to undergo spontaneous arrest of disease. Early lesions grew 46× faster when still limited to the splenium, genu of the corpus callosum, or the brainstem (p = 0.001).ConclusionWe provide a description of CCALD lesion development in a cohort of asymptomatic boys. Understanding the early stages of CCALD is crucial to optimize treatments for children diagnosed by newborn screening.
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Harat, Maciej, Andrzej Lebioda, Judyta Lasota, and Roman Makarewicz. "Evaluation of brain edema formation defined by MRI after LINAC-based stereotactic radiosurgery." Radiology and Oncology 51, no. 2 (May 24, 2017): 137–41. http://dx.doi.org/10.1515/raon-2017-0018.
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Abstract Background Peri-lesional edema is a serious and well-known complication of stereotactic radiosurgery (SRS). Here we evaluated edema risk after SRS and assessed its formation and resolution dynamics. Patients and methods 107 patients underwent SRS for heterogeneous diagnoses: 34 (29%) with arteriovenous malformations, 38 (35%) with meningiomas, 16 (15%) with metastatic tumors, 16 (15%) with acoustic neuromas, 3 with (3%) cavernomas, and 2 (2%) each with anaplastic astrocytomas and anaplastic oligoastrocytomas. Edema area was delineated in MRI T2-FLAIR sequences 0, 6, 12, 18, 24, 30, and 38 months after treatment. Lesion location was defined as either above (n = 80) or below (n = 32) the “Frankfurt modified line” (FML). Results 17% of patients developed or had worsening post-treatment edema. Edema volume was maximal at 6 months (mean 7.2, SD 1.2) post radiosurgery. Post-SRS edema was 5.1 (1.06 – 24.53) times more likely in patients with lesions above the FML. There was no association between edema development and age, PTV size, number of beams, and diagnosis (p = 0.07). Conclusions Radiosurgery-associated edema develops within 6 months of treatment and decreases over time. Edema occurrence is strongly related to lesion location, and its presence is much more likely when the treated lesions are situated above the Frankfurt line.
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Torres, Vitor Lima, Paulo Victor Silva Moraes, Victor Machado de Carvalho, Alexandre Tavares Camelo Oliveira, Rodrigo Fonseca de Medeiros Guedes, Adriana de Queiroz Pinheiro, and Tiago Cunha Ferreira. "Quérion dermatofítico em cadela: Relato de caso." Pubvet 15, no. 1 (January 2021): 1–6. http://dx.doi.org/10.31533/pubvet.v15n01a731.1-6.
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A dermatofitose é uma afecção fúngica que pode acometer cães e gatos de diversas idades. Uma apresentação pouco comum para esta doença é sua forma nodular, chamada quérion. Diversas técnicas são indicadas na literatura para o diagnóstico, dentre elas destaca-se a citologia por ser uma técnica de simples execução, pouco dispendiosa e rápida. Neste relato uma fêmea canina foi atendida apresentando um aumento de volume em região de pálpebra superior direita. Ao exame físico dermatológico, a lesão encontrava-se alopécica e inflamada, com presença de conteúdo viscoso à palpação, sendo compatível com quérion dermatofítico. Foi realizado exame citológico com punção por agulha fina, bem como cultura fúngica da secreção proveniente da lesão. A avaliação citológica revelou infiltrado inflamatório e estruturas compatíveis com artroconídeos fúngicos. Após 30 dias da semeadura ocorreu crescimento de colônias de Microsporum canis. A terapia da paciente baseou-se no uso de Itraconazol em suspensão (10mg/kg/dia) por um período de 45 dias. Ao final do tratamento obteve-se cura clínica, com ausência de processo inflamatório e total repilação do local lesionado.
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Voyten, Jamie, Matthew Peter Holtzman, Liron Pantanowitz, Rajiv Dhir, H. Scott Beasley, Jackie Cuda, and Sara Elizabeth Monaco. "Lessons learned from clinical trial queries on small biopsy collections from an academic cancer center." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e14016-e14016. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e14016.
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e14016 Background: Small biopsies and cytology specimens are becoming increasingly important for clinical trials and biomarker testing. Thus, institutions must ensure that there is adequate lesional material meeting specifications for a multitude of different protocols, which can involve rapid on-site evaluation (ROSE). The aim of this study is to look at the recent clinical trial biopsy characteristics and feedback on these collections at our institution. Methods: Clinical trial biopsies performed at our institution and trial feedback (so called “queries”) were analyzed from the past two years (2017-2019). The query data was reviewed in detail, in addition to protocol modifications related to biopsy requirements and study protocol changes. Results: A total of 698 biopsy collections were performed for clinical trial purposes for 95 trials, with the majority of these requiring biopsies at more than 1 time point (63.2%), for phase 1 or 2 trials (92.6%), and for specific tumor types (67.4%). Only 18 (18.9%) of the 95 trials requiring fresh tissue biopsies provided feedback. This included 90 (12.9%) cases, of which 27 (30.0%) had queries regarding insufficient (10, 37.0%) or borderline (17, 63.0%) tumor, and only 1 (3.7%) of these had ROSE by cytology. ROSE was performed due to institutional guidelines (45.3%), requirement by study (1.1%), or trial modification (5.3%).(Table). Conclusions: This investigation shows the high volume of clinical trial biopsies managed at our academic cancer center. Feedback from trials is low at 18.9%, and frequently involves suboptimal cases without ROSE at acquisition, which has led to more widespread adoption of ROSE to mitigate insufficient biopsies and repeat procedures. The high volume of clinical trial biopsies and variability in trial needs necessitates a collaborative multi-disciplinary network to facilitate these important biopsies for cancer patients. [Table: see text]
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Hagens, Marloes H. J., Sandeep S. V. Golla, Bieneke Janssen, Danielle J. Vugts, Wissam Beaino, Albert D. Windhorst, James O’Brien-Brown, et al. "The P2X7 receptor tracer [11C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study." European Journal of Nuclear Medicine and Molecular Imaging 47, no. 2 (November 8, 2019): 379–89. http://dx.doi.org/10.1007/s00259-019-04550-x.
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Abstract Purpose The novel PET tracer [11C]SMW139 binds with high affinity to the P2X7 receptor, which is expressed on pro-inflammatory microglia. The purposes of this first in-man study were to characterise pharmacokinetics of [11C]SMW139 in patients with active relapsing remitting multiple sclerosis (RRMS) and healthy controls (HC) and to evaluate its potential to identify in vivo neuroinflammation in RRMS. Methods Five RRMS patients and 5 age-matched HC underwent 90-min dynamic [11C]SMW139 PET scans, with online continuous and manual arterial sampling to generate a metabolite-corrected arterial plasma input function. Tissue time activity curves were fitted to single- and two-tissue compartment models, and the model that provided the best fits was determined using the Akaike information criterion. Results The optimal model for describing [11C]SMW139 kinetics in both RRMS and HC was a reversible two-tissue compartment model with blood volume parameter and with the dissociation rate k4 fixed to the whole-brain value. Exploratory group level comparisons demonstrated an increased volume of distribution (VT) and binding potential (BPND) in RRMS compared with HC in normal appearing brain regions. BPND in MS lesions was decreased compared with non-lesional white matter, and a further decrease was observed in gadolinium-enhancing lesions. In contrast, increased VT was observed in enhancing lesions, possibly resulting from disruption of the blood-brain barrier in active MS lesions. In addition, there was a high correlation between parameters obtained from 60- to 90-min datasets, although analyses using 60-min data led to a slight underestimation in regional VT and BPND values. Conclusions This first in-man study demonstrated that uptake of [11C]SMW139 can be quantified with PET using BPND as a measure for specific binding in healthy controls and RRMS patients. Additional studies are warranted for further clinical evaluation of this novel neuroinflammation tracer.
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Leal Verdugo, Camilo Adolfo, and Diego Mauricio Chaustre Ruiz. "Trauma raquimedular y rehabilitación cardiopulmonar." Revista Colombiana de Médicina Física y Rehabilitación 30, no. 1 (September 9, 2020): 54–66. http://dx.doi.org/10.28957/rcmfr.v30n1a5.
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Las personas con lesión medular presentan alteraciones cardiopulmonares y físicas más allá del compromiso motor secundario derivado de la lesión medular; ello genera desacondicionamiento, alteraciones de la dinámica respiratoria y del volumen sanguíneo circu- lante, y sedentarismo, lo cual aumenta el riesgo cardiovascular. El ejercicio es una herramienta demanejo de estas alteraciones con escasa difusión clínica. Se describe su importancia para el paciente lesionado medular, los mecanismos de evaluación funcional y la formulación del ejercicio. Los beneficios son la optimización del gasto cardiaco y el balance respiratorio muscular, así como la mejora en el desempeño de las actividades básicas cotidianas y su funcionalidad relacionada con dispositivos de marcha y movilidad. La valoración funcional tiene protocolos específicos dependientes del nivel de lesión, así como la prescripción del ejercicio. Los programas de rehabilitación cardiaca y pulmonar, así como la prescripción del ejercicio, deben ser considerados en los programas de rehabilitación y manejo del paciente con lesión medular.
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Xie, Yu, Julien Oster, Emilien Micard, Bailiang Chen, Ioannis K. Douros, Liang Liao, François Zhu, et al. "Impact of Pretreatment Ischemic Location on Functional Outcome after Thrombectomy." Diagnostics 11, no. 11 (November 4, 2021): 2038. http://dx.doi.org/10.3390/diagnostics11112038.
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Pretreatment ischemic location may be an important determinant for functional outcome prediction in acute ischemic stroke. In total, 143 anterior circulation ischemic stroke patients in the THRACE study were included. Ischemic lesions were semi-automatically segmented on pretreatment diffusion-weighted imaging and registered on brain atlases. The percentage of ischemic tissue in each atlas-segmented region was calculated. Statistical models with logistic regression and support vector machine were built to analyze the predictors of functional outcome. The investigated parameters included: age, baseline National Institutes of Health Stroke Scale score, and lesional volume (three-parameter model), together with the ischemic percentage in each atlas-segmented region (four-parameter model). The support vector machine with radial basis functions outperformed logistic regression in prediction accuracy. The support vector machine three-parameter model demonstrated an area under the curve of 0.77, while the four-parameter model achieved a higher area under the curve (0.82). Regions with marked impacts on outcome prediction were the uncinate fasciculus, postcentral gyrus, putamen, middle occipital gyrus, supramarginal gyrus, and posterior corona radiata in the left hemisphere; and the uncinate fasciculus, paracentral lobule, temporal pole, hippocampus, inferior occipital gyrus, middle temporal gyrus, pallidum, and anterior limb of the internal capsule in the right hemisphere. In conclusion, pretreatment ischemic location provided significant prognostic information for functional outcome in ischemic stroke.
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Kim, Dong Wook, So-Hyang Im, Jeong-Yeon Kim, Dong-Eog Kim, Goo Taeg Oh, and Sang-Wuk Jeong. "Decreased brain edema after collagenase-induced intracerebral hemorrhage in mice lacking the inducible nitric oxide synthase gene." Journal of Neurosurgery 111, no. 5 (November 2009): 995–1000. http://dx.doi.org/10.3171/2009.3.jns081285.
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Object Hematoma size and brain edema after intracerebral hemorrhage (ICH) are important prognostic factors. Inducible nitric oxide synthase (iNOS) is induced after cerebral ischemia and is known to be involved in secondary neuronal injury, but its significance in ICH is unknown. The authors tested whether iNOS would influence hematoma size and brain edema after ICH. Methods The authors used C57BL/6 and iNOS knockout mice for all the experiments. Experimental ICH was induced by the intrastriatal stereotactic administration of bacterial collagenase. Brain tissue was obtained at 72 hours after ICH. The volume of hematoma was quantified by spectrophotometric assay, and the brain water content was measured. The investigators also measured blood-brain barrier permeability using Evans blue dye. Results There was no significant difference in hematoma size between the 2 groups. The brain water content of the lesional hemisphere was higher in C57BL/6 mice than in iNOS knockout mice. More Evans blue leakage in the brain was observed in C57BL/6 control mice than in iNOS knockout mice. Immunohistochemistry showed iNOS immunoreactivity in the perihematoma areas of C57BL/6 mice but not in the iNOS knockout mice. Conclusions When hematoma size was similar, iNOS knockout mice had significantly less brain edema than their littermates. These results suggest that iNOS modulation might become an antiedematous therapy for ICH.
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Bodini, Benedetta, Francesca Branzoli, Emilie Poirion, Daniel García-Lorenzo, Mélanie Didier, Elisabeth Maillart, Julie Socha, et al. "Dysregulation of energy metabolism in multiple sclerosis measured in vivo with diffusion-weighted spectroscopy." Multiple Sclerosis Journal 24, no. 3 (April 10, 2017): 313–21. http://dx.doi.org/10.1177/1352458517698249.
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Objective: We employed diffusion-weighted magnetic resonance spectroscopy (DW-MRS), which allows to measure in vivo the diffusion properties of metabolites, to explore the functional neuro-axonal damage and the ongoing energetic dysregulation in multiple sclerosis (MS). Methods: Twenty-five patients with MS and 18 healthy controls (HC) underwent conventional magnetic resonance imaging (MRI) and DW-MRS. The apparent diffusion coefficient (ADC) of total N-acetyl-aspartate (tNAA) and creatine–phosphocreatine (tCr) were measured in the parietal normal-appearing white matter (NAWM) and in the thalamic grey matter (TGM). Multiple regressions were used to compare metabolite ADCs between groups and to explore clinical correlations. Results: In patients compared with HCs, we found a reduction in ADC(tNAA) in the TGM, reflecting functional and structural neuro-axonal damage, and in ADC(tCr) in both NAWM and TGM, possibly reflecting a reduction in energy supply in neurons and glial cells. Metabolite ADCs did not correlate with tissue atrophy, lesional volume or metabolite concentrations, while in TGM metabolite ADCs correlated with clinical scores. Conclusion: DW-MRS showed a reduction in tCr diffusivity in the normal-appearing brain of patients with MS, which might reflect a state of ongoing energy dysregulation affecting neurons and/or glial cells. Reversing this energy dysregulation before neuro-axonal degeneration arises may become a key objective in future neuroprotective strategies.
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Iino, Shiro, Suguru Sato, Natsuki Baba, Naoki Maruta, Wataru Takashima, Noritaka Oyama, Takahiro Kiyohara, Masato Yasuda, and Minoru Hasegawa. "Two-phase Surgery Using a Dermal Regeneration Material for Nail Unit Melanoma: Three Case Reports." Open Dermatology Journal 11, no. 1 (October 31, 2017): 81–86. http://dx.doi.org/10.2174/1874372201711010081.
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Background: Nail unit melanoma (NUM) poses a considerable treatment challenge, particularly in cases with in situ or early invasive lesions, and wide excision with phalanx amputation. For post-excisional skin defects, stump plasty and/or split-thickness skin grafting may cause persisted irritation and ulceration as a post-operative complication, because of the insufficient underlying tissue volume, vascularity, and stability. Objective: To seek out other superior management avoiding disadvantages associated with the conventional NUM surgery. Method: Three consecutive cases with NUM were treated by a novel two-phase surgical procedure using a commercially available dermal regeneration template; as the first phase, the lesional nail unit was excised and subsequently covered by a dermal regeneration template onto the phalangeal bone surface, allowing development of robust granulation with extracellular matrix and vascular network. Thereafter, the second phase employed a full-thickness skin grafting. Results: All three cases accomplished complete removal of the NUM lesion, and achieved a good cosmetic and functional outcome, maintaining physiological firmness, contour, and less contraction and atrophy of the overlying skin. They did not complain of major post-operative complications. Conclusion: Our two-phase approach using a dermal regeneration material is a satisfactory and straightforward technique, achieving a substantial benefit functionally and cosmetically in the post-operative period. We propose that the additional use of a tissue regeneration material can provide superior results for the reconstruction step of excised NUM.
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Pincelli, Thais P. "Platelet Rich Plasma in the Treatment of Frontal Fibrosing Alopecia." Clinical Dermatology and Therapy 7, no. 3 (December 31, 2021): 1–3. http://dx.doi.org/10.24966/cdt-8771/100091.
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Frontal Fibrosing Alopecia (FFA) represents a form of scaring alopecia more frequent in postmenopausal women that presents with frontal hairline recession. It is typically classified as a variant of lichen planopilaris. Treatment of FFA can be challenging with poor long-term outcomes. Platelet-Rich Plasma (PRP) consists of an autologous concentration of platelets in a small volume of plasma. Activated platelets secrete cytokines and growth factors and thus may have a potential role in the treatment of inflammatory scarring alopecia such as FFA. A 68-year-old female with multi-resistant FFA was treated with lesional PRP injections every 4 weeks for 16 weeks. Baseline LPPAI score and phototrichograms targeting a representative area of disease activity were compared at baseline and at 16 weeks. After 16 weeks, no significant change in follicular units or follicular density from baseline to week 16 was noted. Only a minimal improvement in inflammatory activity observed clinically and through the Lichen Planopilaris Activity Index was observed. The discordance between the follicular density count and observed inflammatory activity suggests a longer treatment and observational period is needed. Additionally, the frequency of PRP injections potentially may also need to be increased. Given the limited efficacy of current therapies for FFA, PRP injections may be an option in patients with refractory disease, as an adjunct to systemic therapy. Additional investigation is needed to optimize frequency of PRP injections in FFA and to better assess its true anti-inflammatory effect.
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Venegas, Fábio, and João Carlos Cury Saad. "FUNGIGAÇÃO NO CONTROLE DO MOFO BRANCO E PRODUTIVIDADE DO FEIJOEIRO EM CONDIÇÕES DE CERRADO BRASILEIRO." IRRIGA 15, no. 2 (June 17, 2010): 159–72. http://dx.doi.org/10.15809/irriga.2010v15n2p159.
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O presente estudo objetivou determinar a severidade da doença mofo branco (Sclerotinia sclerotiorum (Lib.) de Bary) e os componentes de produção do feijoeiro (Phaseolus vulgaris L.), var. Pérola, submetido a aplicação do fungicida procimidone (Sialex 500), via fungigação (pivô central) e pulverizador automotriz (Uniport). O estudo foi realizado sob condições de produção comercial em campo, no município de Primavera do Leste - MT. O experimento constou de 5 tratamentos (com 4 repetições de 4 ha cada), sendo 4 deles envolvendo duas aplicações de procimidone (1,2 kg ha -1 cada aplicação), aos 42 dias e aos 52 dias após o plantio (DAP), e um deles sem aplicação deste produto, com delineamento experimental de blocos casualizados. Foram testadas as lâminas de água de 5,5 e 11,0 mm na aplicação via pivô central, proporcionando assim volume de calda de 55.000 e 110.000 L ha -1, respectivamente, e os volumes de 120 e 200 L ha -1 de calda no pulverizador automotriz. O critério adotado em todas as avaliações da severidade da doença foi o da porcentagem da área foliar lesionada utilizando escala diagramática de severidade da doença mofo branco. Os valores foram usados para calcular a área abaixo da curva de progresso de doença (AACPD). Foram analisados também, o número dos apotécios do fungo durante o ciclo da cultura e o peso dos escleródios residuais do patógeno na colheita. Nesta ocasião foram avaliados os seguintes componentes da produção da cultura: número de plantas por parcela (stand final), número de vagens por planta, número de grãos por vagem, peso médio de 200 grãos e produtividade de grãos. Os valores da AACPD, apotécios aos 42, 49 e 56 DAP, escleródios em 2 kg de solo e os parâmetros de produtividade da cultura foram submetidos à análise de variância e ao teste de comparação de médias de Tukey no nível de 5 % de significância, utilizando o programa computacional STAT. Nas condições experimentais em que se desenvolveu o trabalho, não foram constatadas diferenças significativas entre as diferentes técnicas de aplicação estudadas em relação ao parâmetros de produtividade, porém, melhores resultados de controle da doença mofo branco, menor número de apotécios por m2 aos 49 e 56 DAP e menor peso dos escleródios residuais na colheita foram obtidos com a aplicação do fungicida via pivô central, independentemente do volume de calda utilizado. UNITERMOS: Phaseolus vulgaris L., Sclerotinia sclerotiorum (Lib.) de Bary, fungigação. VENEGAS, F; SAAD, J. C. C. WHITE MOLD CONTROL USING FUNGIGATION AND YIELD BEAN IN BRAZILIAN SAVANNAH CONDITIONS. 2 ABSTRACT The aim of this research was to evaluate the white mold severity (Sclerotinia sclerotiorum (Lib.) of Bary), bean production components and yield (Phaseolus vulgaris L.), variety Perola, according to the application of procimidone fungicide (Sialex 500), through fungigation (center pivot) and automotive sprayer (Uniport). The study was carried under field production commercial conditions, in Primavera do Leste - MT - Brazil. The experiment consisted of 5 treatments (with 4 repetitions of 4 ha each), all with two procimidone applications (1.2 kg ha-1 each application, same as, 0.6 kg a.i. per hectare) to the 42 and 52 days after seeding. The water depths of 5.5 and 11.0 mm were tested in the application through central pivot (this had your checked uniformity), providing volumes of 55.000 and 110.000 L ha-1, respectively, and the volumes of 120 and 200 L ha-1 in the automotive sprayer. The severity of disease was evaluated by the percentage of the area affected by plant damage using diagramatic grade scale of white mold severity, as described by Azevedo (1998). The values were used to calculate the area under the disease progress curve (AUDPC). They were also analyzed, the number of the fungus apothecia during the crop cycle and the residual sclerotias weight in harvest. On this occasion, it was also evaluated the crop yield parameters: number of plants per plot (final stand), pods per plant, grains per pod, medium weight of 200 grains and productivity of grains. The AUDPC values, apothecia to 42, 49 and 56 days after seeding, sclerotias in 2 soil kg and the crop productivity parameters were submitted to the variance analysis and Tukey Test at 0.05 of probability. This test was also applied in the comparison among the different fungicide application methods, independent of spray volumes in each one. The statistical processing was accomplished by STAT program. The results showed that weren't differences among application techniques studied in relation to productivity parameters, however, best white mold control, smaller apothecia number to 49 and 56 days after seeding and smaller weight of residual sclerotias in the harvest were obtained with the fungigation, independently of the spray volume used. KEYWORDS: Phaseolus vulgaris L., Sclerotinia sclerotiorum (Lib.) de Bary, fungigation.
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Wetz, Christoph, Julian Rogasch, Philipp Genseke, Imke Schatka, Christian Furth, Michael Kreissl, Henning Jann, Marino Venerito, and Holger Amthauer. "Asphericity of Somatostatin Receptor Expression in Neuroendocrine Tumors: An Innovative Predictor of Outcome in Everolimus Treatment?" Diagnostics 10, no. 9 (September 22, 2020): 732. http://dx.doi.org/10.3390/diagnostics10090732.
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Background: in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET), the mTOR inhibitor everolimus is associated with significant improvement in progression-free survival (PFS). This study evaluated the lesional asphericity (ASP) in pretherapeutic somatostatin receptor (SSR) imaging as the first imaging-based prognostic marker for PFS. Methods: this retrospective bicentric cohort study included 30 patients (f = 13, median age, 66.5 (48–81) years) with pretherapeutic [111In-DTPA0]octreotide scintigraphy (Octreoscan®). ASP of functional volumes of up to three leading lesions per patient (n = 74) was calculated after semiautomatic, background-adapted segmentation. Uni- and multivariable Cox regression regarding PFS for clinical factors and the maximum ASP per patient was obtained. Results: all 30 patients showed metachronous or progressive liver metastases. ASP, primary tumor site, metastases pattern, and prior peptide receptor radionuclide therapy (PRRT) were significantly associated with PFS in univariable Cox regression. Only ASP > 12.9% (hazard ratio (HR), 3.33; p = 0.024) and prior PRRT (HR, 0.35; p = 0.043) remained significant in multivariable Cox. Median PFS was 6.7 months for ASP > 12.9% (95% confidence interval (CI), 2.1–11.4 months) versus 14.4 (12.5–16.3) months for ASP ≤ 12.9% (log-rank, p = 0.028). Conclusion: pretherapeutic ASP of SSR positive lesions independently predicted PFS for treatment with everolimus in GEP-NET. ASP may supplement risk-benefit assessment before patient inclusion to treatment.
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Demir, Fadime, and Ahmet Yanarateş. "Relationship between FDG-PET/CT and hematological parameters in squamous cell lung cancer without distant metastasis." Medical Science and Discovery 7, no. 6 (June 26, 2020): 520–25. http://dx.doi.org/10.36472/msd.v7i6.391.
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Objective: This study aimed to investigate the relationship between 18Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters and hematological parameters in squamous cell lung cancer without distant metastasis and to investigate the prognostic value of these parameters.
Patients and Methods: This study included 155 patients who underwent 18F-FDG PET/CT imaging for squamous cell lung cancer. Metabolic and hematological parameters were analyzed. Metabolic parameters included maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), total lesional glycolysis (TLG), and maximum tumor-to-blood SUV ratio (SURmax). Hematological parameters included neutrophil, lymphocyte, platelet, neutrophil/lymphocyte count ratio (NLR), and platelet/lymphocyte count ratio (PLR)
Results: Overall survival was significantly shorter in patients with TLG > 194, NLR > 3.3, and PLR > 157.2 (p < 0.001, p = 0.001, and p = 0.001, respectively). There was a poor correlation between TLG and NLR (p < 0.001, r = 0.302), TLG and PLR (p < 0.001, r = 0.304). TLG (> 194; hazard ratio 1.704, 95% CI 1.056–2.751, p = 0.027) and Tumor-Node-Metastasis (TNM)-based staging (stage II; hazard ratio 1.965, 95% CI 0.739–5.227, p = 0.019) were independent prognostic factors for overall survival.
Conclusion: While PET/CT metabolic parameters had both predictive and independent prognostic values in squamous cell lung cancers, PLR and NLR had only predictive values. It shows that PET/CT metabolic parameters related to the course of the disease are more valuable than hematological parameters in squamous cell lung cancer.
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Falcão, Eduardo Martins, Paulo José D’Albuquerque Medeiros, Danilo Passeado Branco Ribeiro, José Renato Moraes Carvalho Barreto Brandão, Alan Robert Moreira Schmitt, and Ramiro Beato Souza. "Reconstrução mandibular após ressecção de extenso Ameloblastoma de ramo: uso de prótese de Metilmetacrilato seguido de instalação de prótese de ATM customizada – relato de caso / Mandibular reconstruction after extensive Ameloblastoma resecetion in mandibular ramus: use of a space maintainer of Polymethylmethacrylate followed by custom TMJ prosthesis installation – case report." Brazilian Journal of Health Review 5, no. 4 (July 19, 2022): 13044–59. http://dx.doi.org/10.34119/bjhrv5n4-087.
Full textAbstract:
O ameloblastoma é um tumor dentário comum, tem um comportamento localmente agressivo e é capaz de causar um extenso envolvimento das mandíbulas. A lesão freqüentemente afeta a mandíbula, especialmente a região molar e o ângulo mandibular. No exame radiográfico, geralmente tem aspecto radiolúcido e multilocular, apresentando na maioria dos casos, expansão cortical e reabsorção radicular dos dentes adjacentes. O objetivo deste artigo é relatar um caso de um paciente de 72 anos, do sexo masculino, leucodermia, com treta no serviço de Cirurgia Oral e Maxilo-facial do Hospital Pedro Ernesto. Na primeira visita, o paciente teve um aumento assintomático de volume no lado direito da face e intraoral. A tomografia computadorizada, havia imagem hipodensa, multiloculada, com perfuração da cortical, estendendo-se da porção posterior do corpo mandibular até o pescoço do côndilo e o processo coronoide à direita. Foi realizada uma biópsia incisional que mostrou o resultado do ameloblastoma multicístico. A equipe decidiu realizar a ressecção do bloco lesional com desmontagem e reconstrução com prótese TMJ personalizada. Devido à burocracia e ao tempo necessário para a aquisição desta prótese, o tratamento foi necessário para a realização de dois tempos cirúrgicos. Portanto, foi decidido ressecar a lesão e realizar a reconstrução temporária do defeito com placa de reconstrução 2,4mm, parafusos bicorticais e polimetilmetacrilato na porção do ramo mandibular e do côndilo. Aproximadamente 6 meses após a cirurgia da lesão para remover a reconstrução final foi realizada com prótese personalizada da ATM. Atualmente, o paciente está com 5 anos de pós-operatório a segunda cirurgia sem evidência de recidiva ou infecção. Apresenta-se com o contorno facial devolvido e função mastigatória satisfatória.
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Novakovic, Nemanja, Joseph R. Linzey, Thomas L. Chenevert, Joseph J. Gemmete, Jonathan P. Troost, Guohua Xi, Richard F. Keep, Aditya S. Pandey, and Neeraj Chaudhary. "White Matter Survival within and around the Hematoma: Quantification by MRI in Patients with Intracerebral Hemorrhage." Biomolecules 11, no. 6 (June 18, 2021): 910. http://dx.doi.org/10.3390/biom11060910.
Full textAbstract:
White matter (WM) injury and survival after intracerebral hemorrhage (ICH) has received insufficient attention. WM disruption surrounding the hematoma has been documented in animal models with histology, but rarely in human ICH with noninvasive means, like magnetic resonance imaging (MRI). A few human MRI studies have investigated changes in long WM tracts after ICH remote from the hematoma, like the corticospinal tract, but have not attempted to obtain an unbiased quantification of WM changes within and around the hematoma over time. This study attempts such quantification from 3 to 30 days post ictus. Thirteen patients with mild to moderate ICH underwent diffusion tensor imaging (DTI) MRI at 3, 14, and 30 days. Fractional anisotropy (FA) maps were used to calculate the volume of tissue with FA > 0.5, both within the hematoma (lesion) and in the perilesional tissue. At day 3, the percentages of both lesional and perilesional tissue with an FA > 0.5 were significantly less than contralateral, unaffected, anatomically identical tissue. This perilesional contralateral difference persisted at day 14, but there was no significant difference at day 30. The loss of perilesional tissue with FA > 0.5 increased with increasing hematoma size at day 3 and day 14. All patients had some tissue within the lesion with FA > 0.5 at all time points. This did not decrease with duration after ictus, suggesting the persistence of white matter within the hematoma/lesion. These results outline an approach to quantify WM injury, both within and surrounding the hematoma, after mild to moderate ICH using DTI MRI. This may be important for monitoring treatment strategies, such as hematoma evacuation, and assessing efficacy noninvasively.