Exploring SARS-CoV-2 infection and vaccine-induced immunity in chronic myeloid leukemia patients: insights from real-world data in Brazil and the United States.

This study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07-4.51; p < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01-3.31; p < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease.

Radioligand Therapy in Lymphoma: Past, Present, and Future.

In the1980s, radiolabeled cells helped understand the pathology of hemato-oncology. In the 1990s, preclinical trials evaluated radiolabeled immunotherapy with monoclonal antibodies (MoAbs) such as anti-CD20 agents labeled with Iodine-131 (Bexxar) or Yttrium-90 (Zevalin). Due to the safe and durable responses of radiolabeled MoAbs, the Food and Drug Administration approved these agents in the 2000s. Despite radioimmunotherapy's long journey, its application has recently decreased. This review will discuss the historical timeline of radioimmunotherapy, debate on advantages and difficulties, and explore trials. We will examine future directions of radioligand therapy in hemato-oncology, considering emerging molecules that may become the next theragnostic trend.

Importance of the lumbar paraspinal muscles on the maintenance of global sagittal alignment after lumbar pedicle subtraction osteotomy.

OBJECTIVE: There are limited data about the influence of the lumbar paraspinal muscles on the maintenance of sagittal alignment after pedicle subtraction osteotomy (PSO) and the risk factors for sagittal realignment failure. The authors aimed to investigate the influence of preoperative lumbar paraspinal muscle quality on the postoperative maintenance of sagittal alignment after lumbar PSO. METHODS: Patients who underwent lumbar PSO with preoperative lumbar MRI and pre- and postoperative whole-spine radiography in the standing position were included. Spinopelvic measurements included pelvic incidence, sacral slope, pelvic tilt, L1-S1 lordosis, T4-12 thoracic kyphosis, spinosacral angle, C7-S1 sagittal vertical axis (SVA), T1 pelvic angle, and mismatch between pelvic incidence and L1-S1 lordosis. Validated custom software was used to calculate the percent fat infiltration (FI) of the psoas major, as well as the erector spinae and multifidus (MF). A multivariable linear mixed model was applied to further examine the association between MF FI and the postoperative progression of SVA over time, accounting for repeated measures over time that were adjusted for age, sex, BMI, and length of follow-up. RESULTS: Seventy-seven patients were recruited. The authors' results demonstrated significant correlations between MF FI and the maintenance of corrected sagittal alignment after PSO. After adjustment for the aforementioned parameters, the model showed that the MF FI was significantly associated with the postoperative progression of positive SVA over time. A 1% increase from the preoperatively assessed total MF FI was correlated with an increase of 0.92 mm in SVA postoperatively (95% CI 0.42-1.41, p < 0.0001). CONCLUSIONS: This study included a large patient cohort with midterm follow-up after PSO and emphasized the importance of the lumbar paraspinal muscles in the maintenance of sagittal alignment correction. Surgeons should assess the quality of the MF preoperatively in patients undergoing PSO to identify patients with severe FI, as they may be at higher risk for sagittal decompensation.

Cleft Lip and Palate Surgery at a Rural African Hospital: A 13-Year Experience From Western Kenya.

INTRODUCTION: Most studies on the treatment of cleft lip and palate (CLP) in low-income and middle-income countries have reported on the experience of urban centers or surgical mission trips to rural locations. There is a paucity of literature on the experience of local teams providing orofacial cleft surgery in rural Sub-Saharan Africa. This study reports the efficacy and cost-effectiveness of cleft surgery performed by an all-local team in rural Kenya. METHODS: A retrospective chart review was performed on all patients who received CLP repair at Kapsowar Hospital between 2011 and 2023. Information regarding patient age, sex, cleft etiology, surgical management, and home location was retrieved. For the most recent year of study (2023), the authors performed a financial audit of all costs related to the performance of unilateral cleft lip surgery. Descriptive statistics were performed. RESULTS: The authors identified 381 CLP surgeries performed on 311 patients (197 male, 63.3%). The most common etiology of the cleft was left unilateral (28.3%). The average age of primary lip repair decreased from 46.3 months in 2008 to 2009 to 20.2 months in 2022 to 2023 ( P <0.001). The average age of primary cleft palate repair decreased from 38.0 months in 2008 to 2009 to 25.3 months in 2022 to 2023 ( P <0.001). Patients traveled from 23 districts to receive treatment. Age of treatment was not different when distinguished by sex, county poverty level, or travel time from the hospital. The total costs associated with cleft lip repair was $201.6. CONCLUSIONS: Adequately staffed hospitals in rural locations can meaningfully address a regional CLP backlog more cost-effectively than surgical mission trips.

The Pattern and Profile of Orofacial Clefts in Somaliland: A Review of 40 Consecutive Cleft Lip and Palate Surgical Camps.

INTRODUCTION: Somaliland is an autonomously run country that is not internationally recognized. As such, it has been largely excluded by global health development programs despite being the world's fourth poorest country. The purpose of this study was to provide the first known description of the pattern and clinical profile of patients with cleft lip and palate from this nation. METHODS: The authors performed a retrospective chart review on all patients who received cleft lip and palate repair by a single surgeon in 40 separate surgical camps at Edna Adan University Hospital in Hargeisa, Somaliland, between 2011 and 2024. Information regarding patient age, sex, cleft etiology, surgical management, and home location was retrieved. Descriptive statistical analysis was performed. RESULTS: A total of 767 patients (495 male, 64.5%) received 787 surgical procedures. The average age of primary surgery was 73.7 months. The most common chief complaint was left cleft lip with cleft palate (316, 41.2%). Males received primary surgery 19.2 months later than did females (73.7 and 54.6 mo, respectively, P <0.001). Patients residing in Hargeisa received their initial procedure an average of 17.8 months younger than those who lived elsewhere in Somaliland (62.9 and 80.7 mo, respectively, P =0.004). CONCLUSIONS: In this severely economically depressed region, patients received treatment at ages that lagged far beyond recommended guidelines. Our finding of earlier treatment for females than males is rare in the literature and likely relates to cultural sex expectations. Patients from rural locations were especially vulnerable to receiving delayed treatment. Further efforts to decrease the burden of craniofacial deformities in Somaliland should be pursued in earnest.

Importance of the cervical paraspinal muscles in postoperative patient-reported outcomes and maintenance of sagittal alignment after anterior cervical discectomy and fusion.

OBJECTIVE: The aim of this study was to investigate the influence of preoperatively assessed paraspinal muscle parameters on postoperative patient-reported outcomes and maintenance of cervical sagittal alignment after anterior cervical discectomy and fusion (ACDF). METHODS: Patients with preoperative and postoperative standing cervical spine lateral radiographs and preoperative cervical MRI who underwent an ACDF between 2015 and 2018 were reviewed. Muscles from C3 to C7 were segmented into 4 functional groups: anterior, posteromedial, posterolateral, and sternocleidomastoid. The functional cross-sectional area and also the percent fat infiltration (FI) were calculated for all groups. Radiographic alignment parameters collected preoperatively and postoperatively included C2-7 lordosis and C2-7 sagittal vertical axis (SVA). Neck Disability Index (NDI) scores were recorded preoperatively and at 2 and 4-6 months postoperatively. To investigate the relationship between muscle parameters and postoperative changes in sagittal alignment, multivariable linear mixed models were used. Multivariable linear regression models were used to analyze the correlations between the changes in NDI scores and the muscles' FI. RESULTS: A total of 168 patients with NDI and 157 patients with sagittal alignment measurements with a median follow-up of 364 days were reviewed. The mixed models showed that a greater functional cross-sectional area of the posterolateral muscle group at each subaxial level and less FI at C4-6 were significantly associated with less progression of C2-7 SVA over time. Moreover, there was a significant correlation between greater FI of the posteromedial muscle group measured at the C7 level and less NDI improvement at 4-6 months after ACDF. CONCLUSIONS: The findings highlight the importance of preoperative assessment of the cervical paraspinal muscle morphology as a predictor for patient-reported outcomes and maintenance of C2-7 SVA after ACDF.

Association Between Severity of Cervical Central Spinal Stenosis and Paraspinal Muscle Parameters in Patients Undergoing Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of this study was to evaluate the association between severity and level of cervical central stenosis (CCS) and the fat infiltration (FI) of the cervical multifidus/rotatores (MR) at each subaxial levels. SUMMARY OF BACKGROUND DATA: The relationship between cervical musculature morphology and the severity of CCS is poorly understood. METHODS: Patients with preoperative cervical magnetic resonance imaging (MRI) who underwent anterior cervical discectomy and fusion (ACDF) were reviewed. The cervical MR were segmented from C3 to C7 and the percent FI was measured using a custom-written Matlab software. The severity of the CCS at each subaxial level was assessed using a previously published classification. Grade 3, representing a loss of cerebrospinal fluid space and deformation of the spinal cord > 25%, was set as the reference and compared to the other gradings. Multivariable linear regression analyses were conducted and adjusted for age, sex, and body mass index. RESULTS: 156 consecutive patients were recruited. A spinal cord compression at a certain level was significantly associated with a greater FI of the MR below that level. After adjustment for the above-mentioned confounders, our results showed that spinal cord compression at C3/4 and C4/5 was significantly associated with greater FI of the MR from C3 to C6 and C5 to C7, respectively. A spinal cord compression at C5/6 or C6/7 was significantly associated with greater FI of the MR at C7. CONCLUSION: Our results demonstrated significant correlations between the severity of CCS and a greater FI of the MR. Moreover, significant level-specific correlations were found. A significant increase in FI of the MR at the levels below the stenosis was observed in patients presenting with spinal cord compression. Given the segmental innervation of the MR, the increased FI might be attributed to neurogenic atrophy. LEVEL OF EVIDENCE: 3.

Montreal cognitive assessment in Brazilian adults with sickle cell disease: The burdens of poor sociocultural background.

Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients (n = 124; 19-70 years; 56 men; 79 SS, 28 SC, 10 S/ß0, 7 S/ß+) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging. The Median MoCA score was 23 (8-30); 70% had a 25-or-less score, suggesting some level of cognitive impairment. There were no significant associations between MoCA results and any clinical or laboratory data in SS and SC patients; however, a significant correlation (P = 0.03) with stroke was found in HbS/ß-thalassemic patients. Correlations were further detected according to sociodemographic conditions, such as age (r = -0.316; P < 0.001), age at first job (r = 0.221; P = 0.018), personal (r = 0.23; P = 0.012) and per capita familiar incomes (r = 0.303; P = 0.001), personal (r = 0.61; P = 0), maternal (r = 0.536; P = 0), and paternal educational status (r = 0.441; P = 0). We further sought independent predictors of performance using multivariable regressions and increased education was an independent predictor of better scores in MoCA (0.8099, 95% confidence interval [CI]: 0.509-1.111). Brain imaging analysis showed significant and progressive atrophy in important cerebral areas related to memory, learning, and executive function. These data point to the high prevalence and impact of cognitive decline in adult SCD patients, mirrored in brain atrophic areas. It is also possible to observe the influence of sociodemographic conditions on patients' cognitive performances and the need for creating focused therapeutic plans that address these deficiencies. Moreover, the absence of a significant correlation of MoCA values with stroke in the SS and SC groups may be related to the worst sociocultural and economic conditions of the Brazilian African descent population, in which the impact of low educational stimulation on cognitive function can outweigh even the anatomical damage caused by the disease.

Assessing Long-Term Volume Retention in Breast Fat Grafting: A Comparative Study of Lipoaspirate Processing Techniques.

INTRODUCTION: Autologous fat grafting is a method of improving aesthetic outcomes after both breast reconstruction and aesthetic surgery through volume enhancement and tissue contouring. Long-lasting effects are linked to greater patient satisfaction and more optimal augmentation results. Harvesting, processing, and injection techniques may all affect the longevity of deformity filling. Our objective is to evaluate the effect of lipoaspirate processing modality on longitudinal volume retention after surgery. METHODS: A prospective, single-institution, randomized control trial placed consented postmastectomy fat grafting patients into 1 of 3 treatment arms (active filtration, low-pressure decantation, and standard decantation) in a 1:1:1 ratio. A preoperative 3-dimensional scan of the upper torso was taken as baseline. At the 3-month postoperative visit, another 3D scan was taken. Audodesk Meshmixer was used to evaluate the volume change. RESULTS: The volume of fat injected during the initial procedure did not differ significantly between the treatment arms (P > 0.05). Both active filtration and low-pressure decantation resulted in higher percentage volume retention than traditional decantation (P < 0.05). Active filtration and low-pressure decantation exhibited comparable degrees of fat maintenance at 3 months (P > 0.05). DISCUSSION: Compared with using traditional decantation as the lipoaspirate purification technique, active filtration and low-pressure decantation may have led to higher levels of cell viability by way of reduced cellular debris and other inflammatory components that may contribute to tissue resorption and necrosis. Further immunohistochemistry studies are needed to examine whether active filtration and low-pressure decantation lead to lipoaspirates with more concentrated viable adipocytes, progenitor cells, and factors for angiogenesis.

Association patterns between lumbar paraspinal muscles and sagittal malalignment in preoperative patients undergoing lumbar three-column osteotomy.

PURPOSE: We aim to investigate the associations between lumbar paraspinal muscles and sagittal malalignment in patients undergoing lumbar three-column osteotomy. METHODS: Patients undergoing three-column osteotomy between 2016 and 2021 with preoperative lumbar magnetic resonance imaging (MRI) and whole spine radiographs in the standing position were included. Muscle measurements were obtained using a validated custom software for segmentation and muscle evaluation to calculate the functional cross-sectional area (fCSA) and percent fat infiltration (FI) of the m. psoas major (PM) as well as the m. erector spinae (ES) and m. multifidus (MM). Spinopelvic measurements included pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), L1-S1 lordosis (LL), T4-12 thoracic kyphosis (TK), spino-sacral angle (SSA), C7-S1 sagittal vertical axis (SVA), T1 pelvic angle (TPA) and PI-LL mismatch (PI - LL). Statistics were performed using multivariable linear regressions adjusted for age, sex, and body mass index (BMI). RESULTS: A total of 77 patients (n = 40 female, median age 64 years, median BMI 27.9 kg/m2) were analyzed. After adjusting for age, sex and BMI, regression analyses demonstrated that a greater fCSA of the ES was significantly associated with greater SS and SSA. Moreover, our results showed a significant correlation between a greater FI of the ES and a greater kyphosis of TK. CONCLUSION: This study included a large patient cohort with sagittal alignment undergoing three-column osteotomy and is the first to demonstrate significant associations between the lumbar paraspinal muscle parameters and global sagittal alignment. Our findings emphasize the importance of the lumbar paraspinal muscles in sagittal malalignment.

Stereo-EEG-based ictal functional connectivity in patients with periventricular nodular heterotopia-related epilepsy.

Nodular heterotopia (NH)-related drug-resistant epilepsy is challenging due to the deep location of the NH and the complexity of the underlying epileptogenic network. Using ictal stereo-electroencephalography (SEEG) and functional connectivity (FC) analyses in 14 patients with NH-related drug-resistant epilepsy, we aimed to determine the leading structure during seizures. For this purpose, we compared node IN and OUT strength between bipolar channels inside the heterotopia and inside gray matter, at the group level and at the individual level. At seizure onset, the channels within NH belonging to the epileptogenic and/or propagation network showed higher node OUT-strength than the channels within the gray matter (p = .03), with higher node OUT-strength than node IN-strength (p = .03). These results are in favor of a "leading" role of NH during seizure onset when involved in the epileptogenic- or propagation-zone network (50% of patients). However, when looking at the individual level, no significant difference between NH and gray matter was found, except for one patient (in two of three seizures). This result confirms the heterogeneity and the complexity of the epileptogenic network organization in NH and the need for SEEG exploration to characterize more precisely patient-specific epileptogenic network organization.

A decade of firearm injuries: Have we improved?

BACKGROUND: Firearm injuries are a growing public health issue, with marked increases coinciding with the coronavirus disease 2019 (COVID-19) pandemic. This study evaluates temporal trends over the past decade, hypothesizing that despite a growing number of injuries, mortality would be unaffected. In addition, the study characterizes the types of centers affected disproportionately by the reported firearm injury surge in 2020. METHODS: Patients 18 years and older with firearm injuries from 2011 to 2020 were identified retrospectively using the National Trauma Data Bank (NTDB®). Trauma centers not operating for the entirety of the study period were excluded to allow for temporal comparisons. Joinpoint regression and risk-standardized mortality ratios (SMR) were used to evaluate injury counts and adjusted mortality over time. Subgroup analysis was performed to describe centers with the largest increases in firearm injuries in 2020. RESULTS: A total of 238,674 patients, treated at 420 unique trauma centers, met inclusion criteria. Firearm injuries increased by 31.1% in 2020, compared to an annual percent change of 2.4% from 2011 to 2019 ( p = 0.01). Subset analysis of centers with the largest changes in firearm injuries in 2020 found that they were more often Level I centers, with higher historic trauma volumes and percentages of firearm injuries ( p < 0.001). Unadjusted mortality decreased by 0.9% from 2011 to 2020, but after controlling for demographics, injury characteristics and physiology, there was no difference in adjusted mortality over the same time period. However, among patients with injury severity scores ≥25, adjusted mortality improved compared with 2011 (SMR of 0.950 in 2020; 95% confidence interval, 0.916-0.986). CONCLUSION: Firearm injuries pose an increasing burden to trauma systems, with Level I and high-volume centers seeing the largest growth in 2020. Despite increasing numbers of firearm injuries, mortality has remained unchanged over the past decade. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Association between severity of the cervical foraminal stenosis and paraspinal muscle parameters in patients undergoing anterior cervical discectomy and fusion.

OBJECTIVE: The cervical multifidus and rotatores muscles are innervated by the posterior rami of the spinal nerves of the corresponding level, and it has been hypothesized that cervical foraminal stenosis (CFS) affecting the spinal nerves results in changes in these muscles. The purpose of this study was to evaluate the relationship between the severity of CFS and fat infiltration (FI) of the multifidus and rotatores muscles. METHODS: Patients who received preoperative cervical MRI, underwent anterior cervical decompression and fusion between 2015 and 2018, and met inclusion and exclusion criteria were included. Multifidus and rotatores muscles were segmented bilaterally from C3 to C7, and the percent FI was measured using custom-written MATLAB software. The severity of the CFS was assessed by the Kim classification. Multivariable linear mixed models were conducted and adjusted for age, sex, BMI, and repeated measures. RESULTS: In total, 149 patients were included. Linear mixed modeling results showed that a more severe CFS at C3-4 was correlated with a greater FI of the multifidus and rotatores muscles at C4 (estimate 0.034, 95% CI 0.003-0.064; p = 0.031), a more severe CFS at C4-5 was correlated with a greater FI of the multifidus and rotatores muscles at C5 (estimate 0.037, 95% CI 0.015-0.057; p < 0.001), a more severe CFS at C5-6 was correlated with a greater FI of the multifidus and rotatores muscles at C6 (estimate 0.041, 95% CI 0.019-0.062; p < 0.001) and C7 (estimate 0.035, 95% CI 0.012-0.058; p = 0.003), and a more severe CFS at C6-7 was correlated with a greater FI of the multifidus and rotatores muscles at C7 (estimate 0.049, 95% CI 0.027-0.071; p < 0.001). CONCLUSIONS: These results demonstrated level- and side-specific correlations between the FI of the multifidus and rotatores muscles and severity of CFS. Given the segmental innervation of the multifidus and rotatores muscles, the authors hypothesize that the observed increased FI could be reflective of changes due to muscle denervation from CFS.

Association Between Cervical Sagittal Alignment and Subaxial Paraspinal Muscle Parameters.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: The authors aim to investigate the association between muscle functional group characteristics and sagittal alignment parameters in patients undergoing anterior cervical discectomy and fusion. SUMMARY OF BACKGROUND DATA: The relationship between the morphology of cervical paraspinal muscles and sagittal alignment is not well understood. MATERIALS AND METHODS: Patients with preoperative cervical magnetic resonance imaging and cervical spine lateral radiographs in standing position who underwent anterior cervical discectomy and fusion between 2015 and 2018 were reviewed. Radiographic alignment parameters included C2 to 7 lordosis, C2 to 7 sagittal vertical axis (SVA), C2 slope, neck tilt, T1 slope, and thoracic inlet angle. Muscles from C3 to C7 were categorized into four functional groups: sternocleidomastoid group, anterior group, posteromedial group, and posterolateral group (PL). A custom-written Matlab software was used to assess the functional cross-sectional area (fCSA) and percent fat infiltration (FI) for all groups. Multivariable linear regression analyses were conducted and adjusted for age, sex, and body mass index. RESULTS: A total of 172 patients were included. Regression analyses demonstrated that a greater C2 to 7 SVA was significantly associated with a greater FI of the anterior group from C3 to C5 and with a higher fCSA of the PL group at C3 to C4, and C6 to 7. A larger C2 slope was significantly correlated with a greater FI of the anterior group at C3 to C4 and a higher fCSA of the PL group from C3 to C5. CONCLUSION: This work proposes new insights into the complex interaction between sagittal alignment and cervical paraspinal muscles by emphasizing the importance of these muscles in sagittal alignment. The authors hypothesize that with cervical degeneration, the stabilizing function of the anterior muscles decreases, which may result in an increase in the compensatory mechanism of the PL muscles. Consequently, there may be a corresponding increase in the C2 to C7 SVA and a larger C2 slope.

Treatment patterns and outcomes for Hodgkin Lymphoma patients aged 60 and older: a report from the Brazilian Prospective Hodgkin Lymphoma Registry.

The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival.

Low SARS-CoV-2 seroprevalence in a cohort of Brazilian sickle cell disease patients: Possible effects of emphasis on social isolation for a population initially considered to be at very high risk.

Despite being initially considered at higher risk for severe COVID-19, sickle cell disease (SCD) patients have mostly presented clinical severity similar to the general population. As their vulnerability to become infected remains uncertain, we assessed the seroreactivity for SARS-CoV-2 to estimate the prevalence of infection and possible phenotypic and socioeconomic determinants for their contagion. Serologic evaluation was performed on 135 patients with an overall prevalence of 11%; positivity was associated with older age and use of public transportation. We speculate that social distancing instructions recommended by our clinic may have contributed to lower levels of infection, but potential protection factors need further investigation.

The "Connectivity Epileptogenicity Index " (cEI), a method for mapping the different seizure onset patterns in StereoElectroEncephalography recorded seizures.

OBJECTIVE: Localization of epileptogenic brain regions is a crucial aim of pre-surgical evaluation of patients with drug-resistant epilepsy. Several methods have been proposed to identify the seizure onset zone, particularly based on the detection of fast activity. Most of these methods are inefficient to detect slower patterns of onset that account for 20-30% of commonly observed Stereo-Electro-Encephalography (SEEG) patterns. We seek to evaluate the performance of a new quantified measure called the Connectivity Epileptogenicity Index (cEI) in various types of seizure onset patterns. METHODS: We studied SEEG recorded seizures from 51 patients, suffering from focal drug-resistant epilepsy. The cEI combines a directed connectivity measure ("out-degrees") and the original epileptogenicity index (EI). Quantified results (Out-degrees, cEI and EI) were compared to visually defined seizure onset zone (vSOZ). We computed recall (sensitivity) and precision (proportion of correct detections within all detections) with vSOZ as a reference. The quality of the detector was quantified by the area under the precision-recall curve. RESULTS: Best results (in terms of match with vSOZ) were obtained for cEI. For seizures with fast onset patterns, cEI and EI gave comparable results. For seizures with slow onset patterns, cEI gave a better estimation of the vSOZ than EI. CONCLUSIONS: We observed that cEI discloses better performance than EI when seizures starts with slower patterns and equal to EI in seizures with fast onset patterns. SIGNIFICANCE: The cEI is a promising new tool for epileptologists, that helps characterizing the seizure onset zone in sEEG, in a robust way despite variations in seizure onset patterns.

Longitudinal sequencing of RUNX1 familial platelet disorder: new insights into genetic mechanisms of transformation to myeloid malignancies.

The mechanisms by which patients with RUNX1 familial platelet disorder with propensity to myeloid malignancies (FPDMM) develop myeloid malignancies (MM) are not fully understood. We report the results of targeted next-generation sequencing on three patients with RUNX1 FPDMM who developed acute myeloid leukaemia or myelodysplastic syndromes (AML/MDS). DNA samples were collected from bone marrow, peripheral blood and buccal swabs at different time points. One patient had clonal haematopoiesis, represented by an SRSF2 p.P95R variant, prior to his AML diagnosis, when he developed an additional NRAS p.G12D variant. His sister presented to us with MDS, with a TET2 p.S471fs and identical NRAS p.G12D variant. The third patient, from another family, had an additional RUNX1 p.R204X and an NFE2 p.Q139fs variant at AML diagnosis. This constitutes the first report of NFE2 variants in AML without extramedullary disease and NRAS variants in AML/MDS in the setting of FPDMM. A systematic review of the literature including our findings distinguishes two genetic landscapes at AML transformation from FPDMM characterized by either the presence or absence of somatic abnormalities in RUNX1 with or without variants in genes usually associated with MM. Whether clonal haematopoiesis precedes transformation only in patients without somatic abnormalities in RUNX1 needs further confirmation.