Acute ischemic stroke and COVID-19 pandemic in Brazil: a comparative study of frequency and risk factors before and during SARS-CoV-2 era.

BACKGROUND: COVID-19 pandemic directly impacted the request for hospital care and medical assistance for several diseases worldwide, as occurred with acute ischemic stroke. The present study sought to compare the incidence and severity of acute ischemic stroke (AIS), in addition to sociodemographic, clinical, and radiological characteristics of patients hospitalized in the prepandemic (2018-2019) and pandemic (2020-2021) eras. METHODS: An incidence case-control, observational, and analytical research was carried out in the Stroke Unit of Hospital Governador Celso Ramos, Florianopolis, Santa Catarina, Brazil, including 171 patients admitted with acute ischemic stroke from April 2018 to April 2019 (prepandemic era) and 148 patients between January 2020 and January 2021 (during pandemic). RESULTS: The mean incidence of AIS hospital admissions was significantly lower in the pandemic period (CI 95%, 0.2 to 5.6; p = 0.04), being lower in the lockdown periods and when the incidence of new COVID-19 cases increased. Besides, referring to AIS severity, the mean areas of AIS were larger during the pandemic period (p < 0.01), especially in August, September, December, and January (p < 0.05). Sociodemographic and clinical variables did not show any difference between the two periods of the study. CONCLUSIONS: Hospital admissions for AIS decreased in the COVID-19 pandemic, mostly during months of higher incidences of new COVID-19 cases. When the incidence of admissions diminished, an increase in the severity of AIS was observed, characterized by larger areas. These findings might contribute to other similar referral centers in managing public policies related to stroke.

Quality of life long after temporal lobe epilepsy surgery.

OBJECTIVES: To identify variables independently associated with a meaningful improvement in QOL long after surgical treatment of drug-resistant MTLE-HS patients. MATERIAL & METHODS: We prospectively evaluated 72 consecutive MTLE-HS surgically treated patients and analyzed pre and post-surgical variables independently associated with a meaningful improvement in QOL evaluated by the Quality of Life in Epilepsy-31 (QOLIE-31) overall score, and its domain scores determined at follow-up after 36 to 131 months (mean 93 months) after surgery. RESULTS: The mean overall QOLIE-31 score and its subdomain scores improved significantly after surgery (p < 0.01), and 55 patients (76.4%) had a meaningful QOL improvement. Being seizure-free (Engel IA) after surgery showed a non-significant association (OR 2.63, CI 95% 0.53 to 13.05, p = 0.23) and lower depressive symptoms a significant association (OR 4.15, CI 95% 1.19 to 14.53, p = 0.03) with meaningful improvement of QOL. CONCLUSIONS: Patients with MTLE-HS who underwent epilepsy surgery show a sustained, meaningful improvement in their QOL. Pre-surgical variables do not predict long-term QOL improvement after surgery. Lower levels of depressive symptoms at postoperative evaluation are associated with meaningful QOL improvement.

Anxiety and depressive symptoms long after mesial temporal epilepsy surgery: A prospective study.

BACKGROUND: Anxiety and depressive symptoms are prevalent in patients with refractory mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) before and after anterior temporal lobectomy (ATL). AIMS: (1) To follow the levels of anxiety and depressive symptoms long-term after ATL among patients with refractory MTLE-HS; (2) To identify pre- and postsurgical variables associated with the levels of anxiety and depressive symptoms after surgery. METHODS: We compared the levels of anxiety and depressive symptoms determined by the Hospital Anxiety and Depression Scale (HADS) before and long after ATL (mean 104 months, range 70-130) in 41 consecutive patients refractory MTLE-HS. The last follow-up was between September 2018 and March 2020. We also determined pre- and postsurgical variables independently associated with the HADS scores after surgery. RESULTS: The scores of HADS and its subdomains related to anxiety and depression decreased significantly (p < 0.01) after ATL. After multiple linear regressions, the HADS-Anxiety scores before surgery (B = 0.47, CI 95% 0.20 to 0.75, p = 0.001) and at follow-up after surgery (B = 0.07, CI 0.00 to 0.14, p = 0.05) remain independently and positively associated with HADS-Anxiety scores after surgery. The HADS-Depression scores after surgery were independently positively associated with HADS-Depression scores before surgery (B = 0.39, CI 95% 0.10 to 0.76, p = 0.01) and worse seizure control after surgery (B = 1.55, CI 95% 0.23 to 2.87, p = 0.02). CONCLUSION: Anxiety and depressive symptoms in patients with MTLE-HS significantly improved after ATL. Presurgical levels of anxiety and depressive symptoms, respectively, were positively associated with the postsurgical levels of those symptoms. Length of follow-up is associated with anxiety, and worse seizure control is associated with depressive symptoms after ATL. The results have implications for the surgical management of MTLE-HS patients.

Female sex is strongly associated with cognitive impairment in HIV infection.

BACKGROUND: Neurocognitive disorders remain frequent despite highly active antiretroviral treatment (HAART). The CNS is known as the sanctuary of HIV infection, where persistent neuroinflammation occurs regardless of viral suppression. Moreover, opportunistic infections, neurovascular damage and HAART neurotoxicity contribute to neurocognitive impairment. Therefore, detailed epidemiological studies might help to elucidate those complex mechanisms. OBJECTIVE: To investigate the prevalence of cognitive impairment and the associated sociodemographic, clinical and neuropsychological variables among HIV-infected patients admitted to a tertiary centre, in southern Brazil. METHODS: An observational, cross-sectional and analytic study was conducted between February 2019 and March 2020, in Hospital Nereu Ramos (HNR), with148 HIV-infected patients. They were interviewed, submitted to the International HIV Dementia Scale (IHDS) and had their medical data analysed. RESULTS: The prevalence of cognitive impairment was 69.6%. It was higher among women (OR = 3.5; 95% CI 1.5-8; p < 0.01), independently of depression, educational status and age. Full years of schooling were strongly associated with IHDS scores (p < 0.01). Patient Health Questionnaire-9 (PHQ-9) scores for depression (p = 0.8), time since HIV diagnosis (p = 0.2), CD4+ cell counts (p = 0.8) and viral load (p = 0.8) were not associated with IHDS scale. CONCLUSION: A high prevalence of cognitive impairment in HIV-infected patients was identified, independently associated with the female sex and fewer years of schooling. Further studies are needed to clarify the differences in the pathophysiology between sexes and the role of cognitive reserve in prevention of cognitive impairment in HIV infection.

How predictable is cognitive performance in Brazilian patients with pharmacoresistant mesial temporal lobe epilepsy?

OBJECTIVE: The objective of the study was to investigate the independent association between clinical, demographic, psychiatric, radiologic, electrophysiological, and pharmacologic variables and cognitive performance of Brazilian patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE). METHODS: Ninety-three patients with pharmacoresistant MTLE related to hippocampal sclerosis (HS) were included in the study. Multiple linear regressions were done to identify predictor variables for 24 cognitive tests. Independent variables analyzed were sex, hand dominance, age, years of education, marital status, work activity, history for an initial precipitant injury (IPI), family history of epilepsy, lesion side, antiseizure medication (ASM) treatment type, ASM serum levels, benzodiazepine (BDZ) treatment, age at epilepsy onset, disease duration, monthly frequency of seizures, and Hospital Anxiety and Depression Scale (HADS) scores. RESULTS: Years of education was an independent and positive predictor in 22 of the 24 cognitive tests evaluated. Male sex was also a positive predictor of one cognitive test. Variables negatively associated with cognitive performance were left side lesion (10 tests), disease duration (5 tests), polytherapy (3 tests), ASM serum levels (3 tests), and BDZ treatment or not working (1 test each). The regression model explained between 6% and 44% of the cognitive test scores variation. SIGNIFICANCE: In Brazilian patients with pharmacoresistant MTLE-HS, up to 44% of cognitive test scores variation is predictable by clinical, demographic, psychiatric, radiologic, electrophysiology, and pharmacological variables. The identification of predictors of cognitive performance may be helpful for better planning of patient care.

Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study.

OBJECTIVES: To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients. METHODS: Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS. RESULTS: The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2-14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity. SIGNIFICANCE: These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.

Mitochondrial Respiration Chain Enzymatic Activities in the Human Brain: Methodological Implications for Tissue Sampling and Storage.

Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery.

Variables associated with physical health-related quality of life in Parkinson's disease patients presenting for deep brain stimulation.

Deep brain stimulation (DBS) benefits Parkinson's disease (PD) patient's quality of life specially in domains as mobility, activities of daily living (ADL) and bodily discomfort (BD), but little is known about the variables associated with these HRQOL domains in patients presenting for DBS. The objective is to evaluate variables associated with of HRQOL in a Brazilian sample of PD patients presenting for DBS treatment, specifically in the domains related with motor symptoms. In a cross-sectional study of 59 PD patients evaluated at outpatient Unit for Movement Disorders, multiple linear regression analysis was performed to identify independent variables associated with mobility, ADL and BD domains of the 39-item Parkinson's disease questionnaire (PDQ-39). UPDRS III "on" scores, duration of the disease, age, presence of comorbidities and anxiety and depressive symptoms quantified by hospital anxiety and depression scale (HADS), were the independent variables. In our results, HADS scores were independently associated to mobility domain: ß coefficient 1.36 (95 % CI 0.55-2.15) and BD domain: ß coefficient 1.57 (95 % CI 0.67-2.48). UPDRS III "on" scores were independently associated to mobility domain: 0.42 (95 % CI 0.03-0.81). The model of each multiple linear regression analysis explains 25 % of the mobility domain variability (p < 0.01) and 24 % of the BD domain variability (p < 0.01). Psychiatric symptoms were at least as relevant to quality of life as motor symptoms in PD patients presenting for DBS treatment. The effect of treating these psychiatric symptoms on patients' HRQOL deserves further investigation.

In Vivo Function of PTEX88 in Malaria Parasite Sequestration and Virulence.

Malaria pathology is linked to remodeling of red blood cells by eukaryotic Plasmodium parasites. Central to host cell refurbishment is the trafficking of parasite-encoded virulence factors through the Plasmodium translocon of exported proteins (PTEX). Much of our understanding of its function is based on experimental work with cultured Plasmodium falciparum, yet direct consequences of PTEX impairment during an infection remain poorly defined. Using the murine malaria model parasite Plasmodium berghei, it is shown here that efficient sequestration to the pulmonary, adipose, and brain tissue vasculature is dependent on the PTEX components thioredoxin 2 (TRX2) and PTEX88. While TRX2-deficient parasites remain virulent, PTEX88-deficient parasites no longer sequester in the brain, correlating with abolishment of cerebral complications in infected mice. However, an apparent trade-off for virulence attenuation was spleen enlargement, which correlates with a strongly reduced schizont-to-ring-stage transition. Strikingly, general protein export is unaffected in PTEX88-deficient mutants that mature normally in vitro. Thus, PTEX88 is pivotal for tissue sequestration in vivo, parasite virulence, and preventing exacerbation of spleen pathology, but these functions do not correlate with general protein export to the host erythrocyte. The presented data suggest that the protein export machinery of Plasmodium parasites and their underlying mechanistic features are considerably more complex than previously anticipated and indicate challenges for targeted intervention strategies.

How predictable is the erectile function of patients with epilepsy?

INTRODUCTION: Erectile dysfunction (ED) is often reported by patients with epilepsy and may be related to endocrine system abnormalities, side effects of antiepileptic drugs, psychiatric comorbidities, and family or social difficulties. AIMS: This study aimed to identify independent predictor factors for ED in patients with epilepsy. MAIN OUTCOME MEASURES: the five-question form of the International Index of Erectile Function (IIEF-5). METHODS: Independent predictive factors for ED evaluated by the IIEF-5 questionnaire in 36 patients (mean age: 39 years) with focal epilepsy (mean: 6 seizures/month) were identified by multiple linear regression analysis. RESULTS: Eight (21.1%) patients were asymptomatic. Among the symptomatic patients, 11 (28.9%) had mild dysfunction, 10 (26.3%) had moderate dysfunction, and 9 (23.7%) showed severe ED. The multiple linear regression model including family income (B=0.005; p=0.05), education levels in years (B=0.54; p=0.03), depressive symptoms determined by HADS depression subscale (B=-0.49; p=0.03), and prolactin levels (B=-0.45; p=0.07) showed a moderate association (r=0.64) with the IIEF questionnaire and explained 41% (r(2)=0.41) of its variation. CONCLUSIONS: Erectile dysfunction is highly prevalent in patients with focal epilepsies. Education, depressive symptoms, and prolactin levels can predict erectile dysfunction in up to 41% of patients with epilepsy. This preliminary report justifies further efforts to make a large sample size study to identify independent biomarkers and therapeutic targets for ED treatment in patients with epilepsy.

Prevalence of headache in patients with Parkinson's disease and its association with the side of motor symptom onset.

We compared the lifetime prevalence and the prevalence of headache during the previous year in patients with Parkinson's disease (PD) and control subjects. We also investigated the association between the side of PD symptom onset and the side of the headache. We interviewed 98 consecutive patients with an established diagnosis of PD between December 2010 and January 2012. The control group consisted of the 98 oldest sex-matched individuals from the nationwide Brazilian headache database. PD patients showed a significantly lower prevalence (40.8%) of headache in the previous year than controls (69.4%) (adjusted OR 0.5, CI 95% 0.2-0.9, p = 0.03). PD patients also showed a lower prevalence of headache throughout life (74.5%) than controls (93.9%) (adjusted OR 0.2, CI 95% 0.1-0.6, p = 0.01). Considering only patients who presented headache during the previous year, PD patients showed a higher association with occurrence of migraine than tension-type headache compared with controls (adjusted OR 3.3, CI 95% 1.2-8.9, p = 0.02). The headache side was ipsilateral to the side of PD onset in 21 patients (84%), with a concordance of 85.7% on the left side and 81.8% on the right side (p < 0.01). The prevalence of primary headache was significantly lower in patients with PD than controls. The predominant side of headache was ipsilateral to the side of initial motor signs of PD.

Herpesvirus Infection of Endothelial Cells as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Understanding the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that a herpesvirus infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment-symptoms consistent with ME/CFS and Long COVID. This paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within the ECs of ME/CFS patients. This review offers conceptual advances by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research toward potentially unexplored avenues in understanding and treating this complex syndrome.

Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy.

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-D-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser(845) in the Ctx and GluR1-Ser(831) in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.

Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses.

ME/CFS is a debilitating chronic condition that often develops after viral or bacterial infection. Insight from the study of Long COVID/Post Acute Sequelae of COVID-19 (PASC), the post-viral syndrome associated with SARS-CoV-2 infection, might prove to be useful for understanding pathophysiological mechanisms of ME/CFS. Disease presentation is similar between the two conditions, and a subset of Long COVID patients meet the diagnostic criteria for ME/CFS. Since Long COVID is characterized by significant vascular pathology - including endothelial dysfunction, coagulopathy, and vascular dysregulation - the question of whether or not the same biological abnormalities are of significance in ME/CFS arises. Cardiac abnormalities have for a while now been documented in ME/CFS cohorts, with recent studies demonstrating major deficits in cerebral blood flow, and hence vascular dysregulation. A growing body of research is demonstrating that ME/CFS is accompanied by platelet hyperactivation, anomalous clotting, a procoagulant phenotype, and endothelial dysfunction. Endothelial damage and dysregulated clotting can impair substance exchange between blood and tissues, and result in hypoperfusion, which may contribute to the manifestation of certain ME/CFS symptoms. Here we review the ME/CFS literature to summarize cardiovascular and haematological findings documented in patients with the condition, and, in this context, briefly discuss the potential role of previously-implicated pathogens. Overall, cardiac and haematological abnormalities are present within ME/CFS cohorts. While atherosclerotic heart disease is not significantly associated with ME/CFS, suboptimal cardiovascular function defined by reduced cardiac output, impaired cerebral blood flow, and vascular dysregulation are, and these abnormalities do not appear to be influenced by deconditioning. Rather, these cardiac abnormalities may result from dysfunction in the (autonomic) nervous system. Plenty of recently published studies are demonstrating significant platelet hyperactivity and endothelial dysfunction in ME/CFS, as well as anomalous clotting processes. It is of particular importance to determine to what extent these cardiovascular and haematological abnormalities contribute to symptom severity, and if these two systems can be targeted for therapeutic purposes. Viral reservoirs of herpesviruses exist in ME/CFS, and most likely contribute to cardiovascular and haematological dysfunction directly or indirectly. This review highlights the potential of studying cardiac functioning, the vasculature, and coagulation system in ME/CFS.

In-Hospital Symptoms of Depression and Anxiety are Strong Risk Factors for Post-Stroke Depression 90 Days After Ischemic Stroke.

Background and Purpose: Acute ischemic stroke (AIS) and depression are the major causes of disability and decreased quality of life worldwide. Psychiatric disorders are common after stroke, especially post-stroke depression (PSD), which affects one-third of survivors. Although frequent, little is known about the real complexity of the pathophysiology and the factors associated with PSD. Methods: This research aimed to provide data about risk factors and predictors of PSD 90 days after AIS. A cohort study was conducted in a tertiary stroke center located in southern Brazil. We interviewed 148 patients with AIS who were consecutively hospitalized between January 2020 and January 2021. The Hospital Anxiety and Depression Scale (HADS) was applied during hospitalization and at follow-up 90 days after AIS. Furthermore, sociodemographic, clinical, and radiological variables were investigated. Predictive factors were assessed using univariate and multivariate linear regression. The impact of the COVID-19 pandemic on the data was also evaluated. Results: The frequency of PSD 90 days after AIS was 33.9%. In-hospital symptoms of depression and anxiety each represented a 2-fold risk for PSD at follow-up. Furthermore, the HADS - anxiety score 90 days after AIS was strongly associated with the HADS - depression value 90 days after stroke (R: .71; B: .56; P < .01). Conclusions: The present study highlighted a noteworthy frequency of PSD 90 days after AIS. Psychiatric variables during hospitalization and in the follow-up appeared to be the leading associated factors with PSD. These data might support the determination of which patients require more psychiatric management.

Genome sequencing reveals molecular subgroups in oral epithelial dysplasia.

This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: "HGD-like cluster" with 4HGD and 2LGD and "LGD-like cluster" with 4 LGD. MLL4 pathogenic variants were exclusively in the "LGD-like cluster". TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.

Determination of acceptable Hounsfield units uncertainties via a sensitivity analysis for an accurate dose calculation in the context of prostate MRI-only radiotherapy.

Radiation therapy is moving from CT based to MRI guided planning, particularly for soft tissue anatomy. An important requirement of this new workflow is the generation of synthetic-CT (sCT) from MRI to enable treatment dose calculations. Automatic methods to determine the acceptable range of CT Hounsfield Unit (HU) uncertainties to avoid dose distribution errors is thus a key step toward safe MRI-only radiotherapy. This work has analysed the effects of controlled errors introduced in CT scans on the delivered radiation dose for prostate cancer patients. Spearman correlation coefficient has been computed, and a global sensitivity analysis performed following the Morris screening method. This allows the classification of different error factors according to their impact on the dose at the isocentre. sCT HU estimation errors in the bladder appeared to be the least influential factor, and sCT quality assessment should not only focus on organs surrounding the radiation target, as errors in other soft tissue may significantly impact the dose in the target volume. This methodology links dose and intensity-based metrics, and is the first step to define a threshold of acceptability of HU uncertainties for accurate dose planning.

Computed tomography synthesis from magnetic resonance imaging using cycle Generative Adversarial Networks with multicenter learning.

Background and Purpose: Addressing the need for accurate dose calculation in MRI-only radiotherapy, the generation of synthetic Computed Tomography (sCT) from MRI has emerged. Deep learning (DL) techniques, have shown promising results in achieving high sCT accuracies. However, existing sCT synthesis methods are often center-specific, posing a challenge to their generalizability. To overcome this limitation, recent studies have proposed approaches, such as multicenter training . Material and methods: The purpose of this work was to propose a multicenter sCT synthesis by DL, using a 2D cycle-GAN on 128 prostate cancer patients, from four different centers. Four cases were compared: monocenter cases, monocenter training and test on another center, multicenter trainings and a test on a center not included in the training and multicenter trainings with an included center in the test. Trainings were performed using 20 patients. sCT accuracy evaluation was performed using Mean Absolute Error, Mean Error and Peak-Signal-to-Noise-Ratio. Dose accuracy was assessed with gamma index and Dose Volume Histogram comparison. Results: Qualitative, quantitative and dose results show that the accuracy of sCTs for monocenter trainings and multicenter trainings using a seen center in the test did not differ significantly. However, when the test involved an unseen center, the sCT quality was inferior. Conclusions: The aim of this work was to propose generalizable multicenter training for MR-to-CT synthesis. It was shown that only a few data from one center included in the training cohort allows sCT accuracy equivalent to a monocenter study.

A deep learning model to generate synthetic CT for prostate MR-only radiotherapy dose planning: a multicenter study.

Introduction: For radiotherapy based solely on magnetic resonance imaging (MRI), generating synthetic computed tomography scans (sCT) from MRI is essential for dose calculation. The use of deep learning (DL) methods to generate sCT from MRI has shown encouraging results if the MRI images used for training the deep learning network and the MRI images for sCT generation come from the same MRI device. The objective of this study was to create and evaluate a generic DL model capable of generating sCTs from various MRI devices for prostate radiotherapy. Materials and methods: In total, 90 patients from three centers (30 CT-MR prostate pairs/center) underwent treatment using volumetric modulated arc therapy for prostate cancer (PCa) (60 Gy in 20 fractions). T2 MRI images were acquired in addition to computed tomography (CT) images for treatment planning. The DL model was a 2D supervised conditional generative adversarial network (Pix2Pix). Patient images underwent preprocessing steps, including nonrigid registration. Seven different supervised models were trained, incorporating patients from one, two, or three centers. Each model was trained on 24 CT-MR prostate pairs. A generic model was trained using patients from all three centers. To compare sCT and CT, the mean absolute error in Hounsfield units was calculated for the entire pelvis, prostate, bladder, rectum, and bones. For dose analysis, mean dose differences of D 99% for CTV, V 95% for PTV, Dmax for rectum and bladder, and 3D gamma analysis (local, 1%/1 mm) were calculated from CT and sCT. Furthermore, Wilcoxon tests were performed to compare the image and dose results obtained with the generic model to those with the other trained models. Results: Considering the image results for the entire pelvis, when the data used for the test comes from the same center as the data used for training, the results were not significantly different from the generic model. Absolute dose differences were less than 1 Gy for the CTV D 99% for every trained model and center. The gamma analysis results showed nonsignificant differences between the generic and monocentric models. Conclusion: The accuracy of sCT, in terms of image and dose, is equivalent to whether MRI images are generated using the generic model or the monocentric model. The generic model, using only eight MRI-CT pairs per center, offers robust sCT generation, facilitating PCa MRI-only radiotherapy for routine clinical use.