Diffuse Large B-Cell Epstein-Barr Virus-Positive Primary CNS Lymphoma in Non-AIDS Patients: High Diagnostic Accuracy of DSC Perfusion Metrics.

BACKGROUND AND PURPOSE: Immunodeficiency-associated CNS lymphoma may occur in different clinical scenarios beyond AIDS. This subtype of CNS lymphoma is diffuse large B-cell and Epstein-Barr virus-positive. Its accurate presurgical diagnosis is often unfeasible because it appears as ring-enhancing lesions mimicking glioblastoma or metastasis. In this article, we describe clinicoradiologic features and test the performance of DSC-PWI metrics for presurgical identification. MATERIALS AND METHODS: Patients without AIDS with histologically confirmed diffuse large B-cell Epstein-Barr virus-positive primary CNS lymphoma (December 2010 to January 2022) and diagnostic MR imaging without onco-specific treatment were retrospectively studied. Clinical, demographic, and conventional imaging data were reviewed. Previously published DSC-PWI time-intensity curve analysis methodology, to presurgically identify primary CNS lymphoma, was used in this particular lymphoma subtype and compared with a prior cohort of 33 patients with Epstein-Barr virus-negative CNS lymphoma, 35 with glioblastoma, and 36 with metastasis data. Normalized curves were analyzed and compared on a point-by-point basis, and previously published classifiers were tested. The standard percentage of signal recovery and CBV values were also evaluated. RESULTS: Seven patients with Epstein-Barr virus-positive primary CNS lymphoma were included in the study. DSC-PWI normalized time-intensity curve analysis performed the best for presurgical identification of Epstein-Barr virus-positive CNS lymphoma (area under the receiver operating characteristic curve of 0.984 for glioblastoma and 0.898 for metastasis), followed by the percentage of signal recovery (0.833 and 0.873) and CBV (0.855 and 0.687). CONCLUSIONS: When a necrotic tumor is found in a potentially immunocompromised host, neuroradiologists should consider Epstein-Barr virus-positive CNS lymphoma. DSC-PWI could be very useful for presurgical characterization, with especially strong performance of normalized time-intensity curves.

Presurgical Identification of Primary Central Nervous System Lymphoma with Normalized Time-Intensity Curve: A Pilot Study of a New Method to Analyze DSC-PWI.

BACKGROUND AND PURPOSE: DSC-PWI has demonstrated promising results in the presurgical diagnosis of brain tumors. While most studies analyze specific parameters derived from time-intensity curves, very few have directly analyzed the whole curves. The aims of this study were the following: 1) to design a new method of postprocessing time-intensity curves, which renders normalized curves, and 2) to test its feasibility and performance on the diagnosis of primary central nervous system lymphoma. MATERIALS AND METHODS: Diagnostic MR imaging of patients with histologically confirmed primary central nervous system lymphoma were retrospectively reviewed. Correlative cases of glioblastoma, anaplastic astrocytoma, metastasis, and meningioma, matched by date and number, were retrieved for comparison. Time-intensity curves of enhancing tumor and normal-appearing white matter were obtained for each case. Enhancing tumor curves were normalized relative to normal-appearing white matter. We performed pair-wise comparisons for primary central nervous system lymphoma against the other tumor type. The best discriminatory time points of the curves were obtained through a stepwise selection. Logistic binary regression was applied to obtain prediction models. The generated algorithms were applied in a test subset. RESULTS: A total of 233 patients were included in the study: 47 primary central nervous system lymphomas, 48 glioblastomas, 39 anaplastic astrocytomas, 49 metastases, and 50 meningiomas. The classifiers satisfactorily performed all bilateral comparisons in the test subset (primary central nervous system lymphoma versus glioblastoma, area under the curve = 0.96 and accuracy = 93%; versus anaplastic astrocytoma, 0.83 and 71%; versus metastases, 0.95 and 93%; versus meningioma, 0.93 and 96%). CONCLUSIONS: The proposed method for DSC-PWI time-intensity curve normalization renders comparable curves beyond technical and patient variability. Normalized time-intensity curves performed satisfactorily for the presurgical identification of primary central nervous system lymphoma.

Neurologic Involvement in COVID-19: Cause or Coincidence? A Neuroimaging Perspective.

The rapid spread of the coronavirus disease 2019 (COVID-19) pandemic has shaken hospitals worldwide. Some authors suggest that neurologic involvement could further complicate the disease. This descriptive study is a cross-sectional review of 103 patients diagnosed with COVID-19 who underwent neuroimaging (of a total of 2249 patients with COVID-19 in our center). Analyzed variables were neurologic symptoms and acute imaging findings. The most frequent symptoms that motivated neuroimaging examinations were mild nonfocal neurologic symptoms, code stroke (refers to patients presenting with signs and symptoms of stroke whose hyperacute assessment and care is prioritized), focal neurologic symptoms, postsedation encephalopathy, and seizures. No cases of encephalitis or direct central nervous system involvement were detected. Thirteen patients presented with acute ischemic events, and 7, with hemorrhagic events; however, most reported multiple vascular risk factors. Despite the large cohort of patients with COVID-19, we found a large number of symptomatic patients with negative neuroimaging findings, and no conclusions can be drawn concerning concrete associations between neuroimaging and COVID-19.

Variability of the Mammalian Target of Rapamycin Inhibitors Is Correlated With Long-Term Renal Graft Survival.

BACKGROUND: Many studies demonstrate the relationship between the high intrapatient variability of calcineurin inhibitor (CNI) levels and poor long-term renal graft outcome. Our objective is to analyze the intrapatient variability observed in the mammalian target of rapamycin inhibitors (mTOR-i) blood levels, to compare the variability of sirolimus (SRL) with that of everolimus (EVL) in kidney transplant patients converted to an mTOR-i, and to analyze whether the coefficient of variation (CV) was correlated with long-term graft survival. METHODS: We analyzed 279 adult renal transplant patients converted to an mTOR-i. CV was calculated using at least 3 blood trough levels between 3 and 18 months postconversion. RESULTS: The mean and median CV of the entire group was 25.54% and 23.7%, respectively. SRL and EVL mean CV was 23.8% and 27.1% (P = .03), respectively. The group of patients into the last tertile with CV> 28.52% presented a lower death-censored graft survival (75.26% vs. 93.01%, P < .0001) with a mean follow-up of 66.5 months. CONCLUSION: The CV of mTOR-i is correlated with long-term renal graft survival, so it should be considered a prognostic factor. SRL has a lower CV than EVL in renal transplant patients converted to mTOR-i in the stable posttransplant phase.

Acute ischiofemoral impingement? / ¿Pinzamiento isquiofemoral agudo?

We report a case of rare clinical entity, which comes within the spectrum of hip impingements. The case deals with a 36 year old female, Olympic athlete, who developed ischiofemoral impingement 14 months after a surgical hamstring reattachment. She was treated conservatively and fully recovered. When looking into literature on this matter, we found that it is probably an under-diagnosed problem, particularly in patients with no history of prior surgery. To our knowledge, this is the first case reported after a hamstrings tendon reattachment.

Cortical and Trabecular Bone Analysis of Patients With High Bone Mass From the Barcelona Osteoporosis Cohort Using 3-Dimensional Dual-Energy X-ray Absorptiometry: A Case-Control Study.

High bone mass (HBM), a rare phenotype, can be detected by dual-energy X-ray absorptiometry (DXA) scanning. Measurements with peripheral quantitative computed tomography at the tibia have found increased trabecular bone mineral density and changes in cortical bone density and structure, all of which lead to increased bone strength. However, no studies on cortical and trabecular bone have been performed at the femur. The recently developed 3-dimensional (3D)-DXA software algorithm quantifies the trabecular and cortical volumetric bone mineral density (vBMD) and the anatomical distribution of cortical thickness using routine hip DXA scans. We analyzed the femurs of 15 women with HBM and 15 controls from the Barcelona Osteoporosis (BARCOS) cohort using the 3D-DXA technique. The mean vBMD of proximal femur was 29.7% higher in HBM cases than in controls for the integral bone, 41.3% higher for the trabecular bone, and 7.3% higher for the cortical bone (p < 0.001). No differences in bone size were detected between cases and controls. Patients with HBM had a thicker cortex and higher trabecular and cortical vBMDs, as measured by 3D-DXA at the femur and compared to controls; bone size was similar in both groups. To the best of our knowledge, this is the first description of trabecular and cortical characteristics of the hip in patients with HBM.

Residual neck disease management in squamous-cell carcinoma of the head and neck treated with radiotherapy plus cetuximab

Purpose. Management of residual neck disease (RND) is one of the unsolved points after bio-radiotherapy (BRT) in loco-regional advanced squamous-cell carcinoma of the head and neck (SCCHN). The aims of the study were to characterize the radiological pattern of response by computed tomography (CT) and to assess the role of positron-emission tomography (PET)/CT in this setting for a better decision-making in the indication of neck dissection (ND). Methods. We retrospectively reviewed 202 patients consecutively diagnosed with node-positive SCCHN (N1: 24; N2: 152; N3: 26) who had been treated with concomitant radiotherapy and cetuximab with or without previous induction chemotherapy between 2006 and 2013. Radiological evaluation after treatment was assessed by standard criteria using CT and in addition by PET/CT when RND was suspected in cases from 2010. Results. There were 42 (21 %) patients who achieved complete response of the primary tumor persisting RND by CT. From this group, 24 patients were managed without PET/CT, leading to the performance of ND in 22 (92 %). On the other hand, 18 patients underwent PET/CT and ND was performed in only 6 (33 %). The overall survival was not different between both groups (p = 0.32). After histological examination and follow-up, PET/CT obtained a positive predictive value of 56 % and a negative predictive value of 89 %. Conclusions. Radiological response after BRT is similar to that after treatment with chemo-radiotherapy, thereby validating in this scenario the accepted CT criteria to define complete response of the neck. However, when RND is suspected by CT, PET/CT is useful to prevent unnecessary ND (AU)

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Preradiotherapy MR Imaging: A Prospective Pilot Study of the Usefulness of Performing an MR Examination Shortly before Radiation Therapy in Patients with Glioblastoma.

BACKGROUND AND PURPOSE: Current protocols in patients with glioblastoma include performing an MR examination shortly after surgery and then 2-6 weeks after ending concomitant chemoradiotherapy. The assessment of this first postradiotherapy examination is challenging because the pseudoprogression phenomenon may appear. The aim of this study was to explore if performing an MR examination shortly before radiation therapy (preradiotherapy MR imaging) could improve the radiologic assessment of patients with glioblastoma. MATERIALS AND METHODS: A preradiotherapy MR imaging examination was prospectively performed before the start of radiation therapy in 28 consecutive patients with glioblastoma who had undergone surgical resection. Tumor response to chemoradiotherapy was assessed twice: with the early postoperative MR examination as baseline and with the preradiotherapy MR imaging examination as baseline. In addition, tumor growth in the preradiotherapy MR imaging examination was evaluated, and its correlation with patient survival was assessed with Kaplan-Meier analysis and Cox regression. RESULTS: Tumor progression after radiation therapy was found in 16 patients, corresponding to pseudoprogression in 7 of them (44%). Four assessments of pseudoprogression switched to partial response or stable disease when preradiotherapy MR imaging was the baseline examination, and the ratio of pseudoprogression was reduced to 25% (3 of 12). Significant differences in survival were found when patients were stratified according to the pattern of tumor growth on preradiotherapy MR imaging (median overall survival "no-growth," 837 days; "focal-growth," 582 days; "global-growth," 344 days; P = .001). CONCLUSIONS: Performing a preradiotherapy MR imaging examination may improve the clinical management of patients with glioblastoma by reducing the ratio of pseudoprogression assessments and providing prognostic information.

Residual neck disease management in squamous-cell carcinoma of the head and neck treated with radiotherapy plus cetuximab.

PURPOSE: Management of residual neck disease (RND) is one of the unsolved points after bio-radiotherapy (BRT) in loco-regional advanced squamous-cell carcinoma of the head and neck (SCCHN). The aims of the study were to characterize the radiological pattern of response by computed tomography (CT) and to assess the role of positron-emission tomography (PET)/CT in this setting for a better decision-making in the indication of neck dissection (ND). METHODS: We retrospectively reviewed 202 patients consecutively diagnosed with node-positive SCCHN (N1: 24; N2: 152; N3: 26) who had been treated with concomitant radiotherapy and cetuximab with or without previous induction chemotherapy between 2006 and 2013. Radiological evaluation after treatment was assessed by standard criteria using CT and in addition by PET/CT when RND was suspected in cases from 2010. RESULTS: There were 42 (21 %) patients who achieved complete response of the primary tumor persisting RND by CT. From this group, 24 patients were managed without PET/CT, leading to the performance of ND in 22 (92 %). On the other hand, 18 patients underwent PET/CT and ND was performed in only 6 (33 %). The overall survival was not different between both groups (p = 0.32). After histological examination and follow-up, PET/CT obtained a positive predictive value of 56 % and a negative predictive value of 89 %. CONCLUSIONS: Radiological response after BRT is similar to that after treatment with chemo-radiotherapy, thereby validating in this scenario the accepted CT criteria to define complete response of the neck. However, when RND is suspected by CT, PET/CT is useful to prevent unnecessary ND.

Proton MR spectroscopy provides relevant prognostic information in high-grade astrocytomas.

BACKGROUND AND PURPOSE: There is a large range of survival times in patients with HGA that can only be partially explained by histologic grade and clinical aspects. This study aims to retrospectively assess the predictive value of single-voxel (1)H-MRS regarding survival in HGA. MATERIALS AND METHODS: Pretreatment (1)H-MRS in 187 patients with HGA produced 180 spectra at STE (30 ms) and 182 at LTE (136 ms). Patients were dichotomized into 2 groups according to survival better or worse than the median. The spectra of the 2 groups were compared using the Mann-Whitney U test. The points on the spectrum with the most significant differences were selected for discriminating patients with good and poor prognosis. Thresholds were defined with ROC curves, and survival was analyzed by using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Four points on the spectrum showed the most significant differences: 0.98 and 3.67 ppm at STE; and 0.98 and 1.25 ppm at LTE (P between <.001 and .011). These points were useful for stratifying 2 prognostic groups (P between <.001 and .003, Kaplan-Meier). The Cox forward stepwise model selected 3 spectroscopic variables: the intensity values of the points 3.67 ppm at STE (hazard ratio, 2.132; 95% CI, 1.504-3.023), 0.98 ppm at LTE (hazard ratio, 0.499; 95% CI, 0.339-0.736), and 1.25 ppm at LTE (hazard ratio, 0.574; 95% CI, 0.368-0.897). CONCLUSIONS: (1)H-MRS is of value in predicting the length of survival in patients with HGA and could be used to stratify prognostic groups.

Correlation of C0 and C2 levels with cyclosporine side effects in kidney transplantation.

Cyclosporine has a narrow therapeutic window requiring close monitoring to ensure adequate immunosuppression while avoiding nephrotoxicity and other side effects. Pharmacokinetic studies have suggested that cyclosporine levels at 2 hours postdose (C2) is the best single time point to predict area under the concentration curve (AUC) in kidney transplant recipients. C2 also predicted acute rejection episodes and nephrotoxicity better than trough levels (C0). Targeting cyclosporine levels to minimize side effects while maintaining adequate immunosuppressive effects is of clinical interest. There are conflicting evidence and few reports about whether cyclosporine-related side effects are a dose-dependent phenomenon. The aim of this single center study was to ascertain whether cyclosporine side effects were dose-dependent and which single time point level (C0 or C2) was more closely related to them. We analyzed 225 patients on Neoral-based immunosuppression with C0 and C2 levels measured on the same day of 2 different visits. Serum creatinine, glucose, uric acid, potassium, total cholesterol, triglycerides, and 24-hour urinary sodium elimination were measured by routine biochemical analyses. Blood pressure was measured at each visit. A significant positive correlation was observed between C2 and C0 concentrations and levels of potassium (P < .001), total cholesterol (P < .001), systolic blood pressure (P < .001), and pulse pressure (P < .01). There was a significant negative correlation between C2 and uric acid (P < .001). AUCs of receiver operating characteristic (ROC) curves for both C2 and C0 levels were significant as predictors of hyperkalemia (P < .001), hyperuricemia (P = .001), hypercholesterolemia (P < .05), and high systolic blood pressure (P < .05). There were no significant differences between the capacities of C2 or C0 to predict these variables. In conclusion, potassium, total cholesterol, uric acid, and systolic hypertension were influenced by cyclosporine in a dose-dependent manner. Both C2 and C0 were useful to predict cyclosporine side effects.

Muerte súbita y epilepsia / Sudden death and epilepsy

La muerte súbita es una de las principales causas de mortalidad en pacientes epilépticos. Se define por su presentación repentina e inesperada, no traumática, con o sin evidencia de crisis, sin que el examen postmortem revele hallazgos anatómicos o toxicológicos como causa de la muerte. En este sentido, los hallazgos de autopsia suelen ser inespecíficos y por lo que respecta al examen neuropatológico, son raros los casos en los que se puede demostrar la presencia de lesiones encefálicas. En este trabajo, presentamos el caso de un varón de 29 años de edad, con antecedentes de enfermedad epiléptica, que falleció de forma súbita e inesperada mientras dormía. El estudio neuropatológico reveló la presencia de anomalías cerebrales en ambos hemisferios que consistían en trastornos de la sulcación y de la migración neuronal. Se realiza la descripción macroscópica de estas malformaciones congénitas, las cuales con frecuencia se manifiestan clínicamente en forma de crisis comiciales (AU)

Sudden unexpected death in epilepsy is one of the main causes of mortality in epileptic patients. It is defined as sudden, unexpected, non-traumatic death in an individual with epilepsy, witnessed or unwitnessed, in which postmortem examination fails to reveal an anatomical or toxicological cause of the death. In this sense, postmortem examination uses to be unspecific and neuropathological findings are unusual. In this paper, a case is presented of a 29-year old male, with a medical history of chronic epilepsy, who died suddenly and unexpectedly during sleep. Neuropathological study showed brain anomalies in both hemispheres related to sulcation and neuronal migration disorders. We report the macroscopical description of these congenital malformations, which have been widely associated with epilepsy (AU)

High initial blood levels of tacrolimus in overweight renal transplant recipients.

For the purpose of both efficacy and safety, exposure to tacrolimus and other immunosuppressive drugs must be monitored, since initial levels influence the development of acute rejection episodes, nephrotoxicity, and posttransplantation diabetes mellitus. The aim of this study was to identify risk factors for developing high initial tacrolimus blood levels. We analyzed clinical and biochemical parameters of 85 renal transplant recipients receiving tacrolimus-based immunosuppressive therapy by stratifying into subgroups of patients who displayed first tacrolimus concentrations higher and lower than 15 ng/mL. Patients with a first level of tacrolimus higher than 15 ng/mL were older (52 +/- 13 vs 40 +/- 12 years, P < .05) and had a larger body mass index (27 +/- 4 vs 23 +/- 3 kg/m2, P < .05) than patients with lower levels, despite receiving a lower weight-adjusted cumulative steroid dose (8.2 +/- 2.2 vs 9.3 +/- 2.5 mg/kg, P < .05). Upon logistic regression, age (RR 1.047, 95% CI 1.007 to 1.08, P = .021) and body mass index (RR 1.176, 95% CI 1.009 to 1.371, P = .036) remained significant risk factors for high initial blood levels of tacrolimus. As these subgroups of patients are most prone to develop posttransplantation glycemic disorders, attention must be paid to avoid high tacrolimus blood levels by diminishing initial tacrolimus doses or estimating them from ideal body weight.

Higher initial tacrolimus blood levels and concentration-dose ratios in kidney transplant recipients who develop diabetes mellitus.

Posttransplantation diabetes mellitus (PTDM) is a common complication of kidney transplantation, associated with poorer graft and patient outcomes. Tacrolimus is a strong immunosuppressive drug associated with low acute rejection rates, but a higher risk for PTDM. High trough levels of tacrolimus during the first month after transplantation have been found to be a significant risk factor for the development of PTDM. The aim of this single-center study was to identify the risk factors for the development of PTDM among kidney transplant recipients under tacrolimus therapy. We examined 73 cadaveric kidney transplant recipients receiving tacrolimus between 1994 and 2003. Age, donor and recipient gender, dialysis method, body mass index (BMI), first year weight gain, mismatches, incidence of acute rejection and delayed graft function, hepatitis C serology, first year cumulative steroid dose, first tacrolimus blood level, first tacrolimus blood level <15 ng/mL, and corresponding tacrolimus daily doses and concentration/dose ratios (CDR) were also collected. PTDM was defined as at least 2 fasting blood glucose values > or =126 mg/dL, according to the World Health Organization criteria. Incidence of first year PTDM was 27.4%. Patients with PTDM showed significantly higher age, BMI, first tacrolimus blood level, first tacrolimus CDR, and CDR with tacrolimus blood level <15 ng/mL as well as less 1-year weight gain. After logistic regression, age (relative risk [RR] 1.060, confidence interval [CI] 95%, 1.001-1.122; P = .043) and first tacrolimus blood level (RR 1.154; CI 95%, 1.038-1.283; P = .008) remain significant risk factors for developing PTDM. Older age and initial tacrolimus blood levels were the main risk factors for PTDM among our group of patients. Kidney transplant recipients who develop PTDM maintain a high CDR of tacrolimus.