Low-risk HPLLs/ABC score patients with splenic marginal zone lymphoma can be safely managed without treatment: Results from a prospective Spanish study.

The aims of our study were to analyse compliance with the 2014 GELTAMO SMZL Guidelines, in patients with splenic marginal zone lymphoma (SMZL), and to evaluate the outcome according to the HPLLs/ABC-adapted therapeutic strategy. Observational prospective multicenter study of 181 SMZL patients diagnosed between 2014 and 2020. Lymphoma-specific survival (LSS), composite event-free survival (CEFS) and response rates were assessed. 57% of the 168 patients included in the analysis followed the Guidelines. The overall response rate was higher in the rituximab chemotherapy and in the rituximab arms compared with the splenectomy arm (p < 0.001). The 5-year overall survival was 77% and the 5-year LSS of 93%. There were no differences in the 5-year LSS according to the treatment received (p = 0.68). The 5-year CEFS in the overall series was 45%, and there were significant differences between scores A and B (p = 0.036). There were no significant differences when comparing LSS and progression-free survival in patients treated with rituximab or rituximab chemotherapy at diagnosis or after observation. Our data support HPLLs/ABC score as a practical tool for the management of SMZL, observation as the best approach for patients in group A and rituximab as the best treatment for group B.

Extranodal natural killer/T-cell lymphoma nasal type in a western population: Molecular profiling identifies new therapeutic targets.

(A) Correlation matrix of unsupervised co-regulated genes, based on the 208 genes included in the NanoString platform. Some of the clusters of co-regulated genes corresponded to the following: Inflammatory cells; Epstein-Barr virus; B-cells; Cytotoxic T-cells; T-cells; and Proliferation. (B) Analysis of genomic alterations by targeted sequencing. Distribution of mutations in the 62 analyzed genes. Rows correspond to sequenced genes, columns represent individual patients. Color coding: green, missense; blue, synonymous; pink, frameshift; violet, Indel; red, stop gained; yellow, UTR.

Blood transfusion activity in a general hospital during the COVID-19 pandemic.

BACKGROUND: The COVID-19 outbreak has affected almost all hospital departments, including transfusion services. However, the demand for transfusions in a general hospital designated to deal with COVID-19 patients has not been analysed before. STUDY DESIGN AND METHODS: A retrospective study was conducted to evaluate blood transfusion practices from 15 March to 14 April 2020 at Hospital Universitario Infanta Leonor (Madrid, Spain). During this month, with few exceptions, the hospital became a 'COVID-19' centre. In addition, transfusion rates during this time frame and the same period over the last 4 years were compared. RESULTS: From 15 March to 14 April 2020, only 254 blood components were transfused, resulting in a 49·3% reduction over the previous year. Interestingly, in critically ill patients, the red blood cell (RBC) transfusion/bed ratio significantly decreased during this period (0·92) compared to the same ratio over the past 4 years (2·70) (P = 0·02). Of note, 106 blood components (95 RBC; 11 platelet concentrates) were transfused to only 36 out of 1348 COVID-19 patients (2·7%). The main reason for RBC transfusion in COVID-19 patients was a previous underlying disease (44%) followed by bleeding (25%) and inflammatory anaemia (25%). CONCLUSION: This is the first study to report a decrease in blood transfusions during the COVID-19 pandemic in a general hospital and especially in the intensive care unit. The results of this study suggest that COVID-19 does not generally induce transfusion requiring anaemia, being the main causes for transfusion in these patients underlying conditions or bleeding.

High penetrance of inferior vena cava system atresia in severe thrombophilia caused by homozygous antithrombin Budapest 3 variant: Description of a new syndrome.

Atresia of inferior vena cava (IVC) is a rare congenital malformation associated with high risk of venous thrombosis that still has unknown etiology, although intrauterine IVC thrombosis has been suggested to be involved. The identification of IVC atresia in a case with early idiopathic venous thrombosis and antithrombin deficiency caused by the homozygous SERPINC1 c.391C > T variant (p.Leu131Phe; antithrombin Budapest 3) encouraged us to evaluate the role of this severe thrombophilia in this vascular abnormality. We have done a cross-sectional study in previously identified cohorts of patients homozygous for the Budapest 3 variant (N = 61) selected from 1118 patients with congenital antithrombin deficiency identified in two different populations: Spain (N = 692) and Hungary (N = 426). Image analysis included computed tomography and phlebography. Atresia of the IVC system was observed in 17/24 cases (70.8%, 95% confidence interval [CI]: 48.9%-87.3%) homozygous for antithrombin Budapest 3 with available computed tomography (5/8 and 12/16 in the Spanish and Hungarian cohorts, respectively), 16 had an absence of infrarenal IVC and one had atresia of the left common iliac vein. All cases with vascular defects had compensatory mechanisms, azygos-hemiazygos continuation or double IVC, and seven also had other congenital anomalies. Short tandem repeat analysis supported the specific association of the IVC system atresia with SERPINC1. We show the first evidence of the association of a severe thrombophilia with IVC system atresia, supporting the possibility that a thrombosis in the developing fetal vessels is the reason for this anomaly. Our hypothesis-generating results encourage further studies to investigate severe thrombophilic states in patients with atresia of IVC.

Can Virtual Assistants Perform Cognitive Assessment in Older Adults? A Review.

Community-dwelling older adults have raised the scientific community's interest during the COVID-19 era as their chronic conditions might be aggravated by the consequences of confinement. Digital devices in this field to monitor cognitive impairment are an emerging reality of an innovative nature. However, some groups may not have benefited from these developments as much as, for example, younger people. The aim of this manuscript is to carry out a review on the development of digital devices, and specifically virtual assistants, for the detection of cognitive impairment in older adults. After a screening process, eight studies were found under the given criteria, and this number was even smaller for those using virtual assistants. Given the opportunities offered by virtual assistants through techniques such as natural language processing, it seems imperative to take advantage of this opportunity for groups such as older adults.

RELINF: prospective epidemiological registry of lymphoid neoplasms in Spain. A project from the GELTAMO group.

Lymphomas are a large, heterogeneous group of neoplasms with well-defined characteristics, and this heterogeneity highlights the importance of epidemiological data. Knowledge of local epidemiology is essential to optimise resources, design clinical trials, and identify minority entities. Given there are few published epidemiological data on lymphoma in Spain, the Spanish Lymphoma and Autologous Bone Marrow Transplant Group created the RELINF project. The aim of this project is to determine the frequencies and distribution of lymphoid neoplasms in Spain and to analyse survival. We developed an online platform for the prospective collection of data on newly diagnosed cases of lymphoma in Spain between January 2014 and July 2018; 11,400 patients were registered. Diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) were the most frequent lymphomas in our series. Marginal B cell lymphoma frequency was higher than that reported in other studies, representing more than 11% of mature B cell lymphomas. Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) was the most common subtype of T cell lymphoma, and NK/T cell lymphomas were more frequent than expected (5.4% of total). Hodgkin's lymphoma accounted for 12% of lymphoproliferative syndromes. Overall survival was greater than 90% at 2 years for indolent B cell lymphomas, and approximately 60% for DLBCL, somewhat lower than that previously reported. Survival was poor for PTCL-NOS and angioimmunoblastic T cell lymphoma, as expected; however, it was somewhat better than that in other studies for anaplastic large cell anaplastic lymphoma kinase lymphomas. This is the first prospective registry to report the frequencies, distribution, and survival of lymphomas in Spain. The frequencies and survival data we report here are globally consistent with that reported in other Western countries. These updated frequencies and survival statistics are necessary for developing appropriate management strategies for neoplasias in the Spanish population.

Prospective Associations between BOLD Markers of Response Inhibition and the Transition to Frequent Binge Drinking.

BACKGROUND: Altered brain activation during response inhibition has been linked to a greater risk for alcohol and other substance use behaviors in late adolescence. However, the ability of neural markers of response inhibition, acquired during adolescence, to temporally predict the transition from less frequent and lower quantity alcohol use to high-risk, frequent (≥ weekly) binge drinking behavior remains unclear. METHODS: Adolescents (N = 29; 9 females) were selected from a larger ongoing longitudinal study to include those who transitioned to at least weekly binge drinking (≥5/4 alcoholic drinks for males/females per occasion) over a 15-year follow-up period. Prior to the onset of weekly binge drinking (mean age = 18.0), participants underwent a functional MRI including a go/no-go task. Whole-brain activation from the no-go correct rejection versus no-go false alarm contrast was used to predict time to transition to frequent binge drinking. RESULTS: Less no-go correct rejection versus no-go false alarm activation in a cluster including the precentral gyri, insula, and inferior frontal gyri predicted a more rapid transition into frequent binge drinking (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05, cluster threshold ≥ 18 voxels). CONCLUSIONS: Results from this study are supported by literature suggesting that frontoinsular involvement is important for successful inhibition and cognitive control. Altered brain activation during response inhibition may thus represent neural antecedents of impulse regulation difficulties related to alcohol consumption. The magnitude of this activation provides temporal information that may be used to inform and optimize timing of interventions aimed at preventing the escalation and transition to problematic drinking for youth who have already begun to engage in drinking behaviors.

Parental Family History of Alcohol Use Disorder and Neural Correlates of Response Inhibition in Children From the Adolescent Brain Cognitive Development (ABCD) Study.

BACKGROUND: Youth whose parents have alcohol use disorder (AUD) are at higher risk for earlier initiation and greater magnitude of alcohol use, and have a higher likelihood of developing an AUD than their peers without parental history of AUD. This increased risk may be partly attributable to altered development of inhibitory control and related neural circuitry. This study examined neural activation during a motor response inhibition Stop Signal Task (SST) in substance-naïve youth aged 9 to 10 years with and without parental family history of AUD. METHODS: Baseline cross-sectional survey and functional magnetic resonance imaging (fMRI) data were drawn from 6,898 youth in the US-based Adolescent Brain Cognitive Development Study. Generalized additive mixed models were conducted to examine the association between maternal, paternal, and parental (both mother and father) family history of AUD with neural activation during successful and failed response inhibition. Family history interactions with sex and stratification by ethnicity were explored. RESULTS: Of 6,898 participants, 951 (14%) were family history positive for any parental AUD. Paternal history of AUD was associated with greater activation for successful inhibition in the right medial orbital frontal gyrus, compared to youth with no family history. Maternal history of AUD was associated with greater activation for failed response inhibition among females in the cerebellum, compared to females with no such history. Parental history (both mother and father) of AUD was associated with greater activation during successful inhibition in the left paracentral gyri and left superior parietal lobule. Maternal history and parental history of AUD findings were accounted for by a family history of substance use disorder in general. All effect sizes were relatively small. CONCLUSIONS: Substance-naïve children with a parental family history of AUD exhibit greater neural activation in some regions of the fronto-basal ganglia and cerebellar networks when they successfully or unsuccessfully inhibit a response as compared to children with no such family history. This unique neural response pattern could reflect a compensatory response and may represent an inherent neurobiological vulnerability to risk-related behaviors in these youth which will be examined in future longitudinal analyses of this cohort.

Life expectancy of follicular lymphoma patients in complete response at 30 months is similar to that of the Spanish general population.

The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10-year period who needed therapy and were treated with rituximab-containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10-year overall survival (OS) of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex- and age-matched Spanish general population.

The Relationship Between Regional Cerebral Blood Flow Estimates and Alcohol Problems at 5-Year Follow-Up: The Role of Level of Response.

BACKGROUND: Acute alcohol consumption is associated with temporarily increased regional cerebral blood flow (CBF). The extent of this increase appears to be moderated by individual differences in the level of response (LR) to alcohol's subjective effects. The low LR phenotype is a known risk factor for the development of alcohol problems. This study investigates how the low LR phenotype relates to the relationship between alcohol-related changes in CBF and alcohol problems 5 years later. METHODS: Young adults (ages 18 to 25) were selected based on their LR to alcohol and underwent a neuroimaging protocol including arterial spin labeling and functional scans. These participants were recontacted ~5 years later and assessed on alcohol outcomes. A final sample of 107 subjects (54 low and 53 high LR subjects) was included in the analyses. Whole-brain analysis revealed 5 clusters of significant alcohol-induced, versus placebo-induced, CBF changes that were consistent with a previous report. Peak alcohol-placebo CBF response was extracted from these regions and, along with the LR group, submitted to a hierarchical linear regression predicting alcohol problems. Analyses controlled for age, sex, and baseline alcohol problems. RESULTS: In the regression analysis, greater alcohol-placebo CBF difference in the right middle/superior/inferior frontal gyri and bilateral anterior cingulate gyri clusters predicted greater future alcohol problems for the low LR group, whereas this relationship was not found to be significant in the high LR group. CONCLUSIONS: This study demonstrates a clinically important relationship between CBF and future alcohol problems, particularly in individuals with a low LR phenotype. These initial results help to elucidate the neurobiological pathways involved in the development of alcohol use disorders for individuals with low LR.

Risk of, and survival following, histological transformation in follicular lymphoma in the rituximab era. A retrospective multicentre study by the Spanish GELTAMO group.

The diagnostic criteria for follicular lymphoma (FL) transformation vary among the largest series, which commonly exclude histologically-documented transformation (HT) mandatorily. The aims of this retrospective observational multicentre study by the Spanish Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea, which recruited 1734 patients (800 males/934 females; median age 59 years), diagnosed with FL grades 1-3A, were, (i) the cumulative incidence of HT (CI-HT); (ii) risk factors associated with HT; and (iii) the role of treatment and response on survival following transformation (SFT). With a median follow-up of 6·2 years, 106 patients developed HT. Ten-year CI-HT was 8%. Considering these 106 patients who developed HT, median time to transformation was 2·5 years. High-risk FL International Prognostic Index [Hazard ratio (HR) 2·6, 95% confidence interval (CI): 1·5-4·5] and non-response to first-line therapy (HR 2·9, 95% CI: 1·3-6·8) were associated with HT. Seventy out of the 106 patients died (5-year SFT, 26%). Response to HT first-line therapy (HR 5·3, 95% CI: 2·4-12·0), autologous stem cell transplantation (HR 3·9, 95% CI: 1·5-10·1), and revised International Prognostic Index (HR 2·2, 95% CI: 1·1-4·2) were significantly associated with SFT. Response to treatment and HT were the variables most significantly associated with survival in the rituximab era. Better therapies are needed to improve response. Inclusion of HT in clinical trials with new agents is mandatory.

Delirium in the acute phase after stroke: comparison between methods of detection.

Delirium is an acute neuropsychiatric syndrome, very common in hospitalized people with medical and neurological conditions. The identification of delirium after stroke is not an easy task and validated psychometric instruments are needed to correctly identify it. We decided to verify if (1) formal training in DSM-V criteria is needed to correctly identify post-stroke delirium, (2) if the use of a brief psychometric instrument such as 4AT improves its identification, (3) the applicability of these scales in the stroke setting. In the first phase of this study we retrospectively studied 102 acute stroke patients in Stroke Units of San Martino Hospital (Genova, Italy) to evaluate delirium with clinical criteria, first by a neurologist without a formal training in DSM-V criteria and after training. Then, we enrolled 100 new acute stroke patients who underwent screening for delirium using 4AT scale and DSM-V criteria. In the first phase, DSM-V criteria training significantly increased the ability to capture delirium (5 vs. 15%). In the second phase, the 4AT was used for delirium screening revealing a 52% of cases of delirium, the same observed by the consensus diagnosis of two senior neurologists (that was 50%). In the second phase, the use of 4AT scale allowed to capture post-stroke delirium as well as the consensus diagnosis by two neurologists. The identification of post-stroke delirium is not an easy task and requires both formal training in DSM-V criteria as well as the application of brief scales, such as the 4AT.

Outcomes and Management of the SARS-CoV2 Omicron Variant in Recipients of Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy.

Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T cell therapy (CAR-T) recipients who develop Coronavirus disease 2019 (COVID-19) can have decreased overall survival (OS), likely due to disease-inherent and therapy-related immunodeficiency. The availability of COVID-19-directed therapies and vaccines have improved COVID-19-related outcomes, but immunocompromised individuals remain vulnerable. Specifically, the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infections, including Omicron and its sublineages, particularly in HCT recipients, remain to be defined. The aim of this study was to compare the impact of SARS-CoV-2 Omicron infections in HCT/CAR-T recipients with outcomes previously reported for ancestral SARS-CoV-2 infections early in the pandemic (March to June 2020). This was a retrospective analysis of adult HCT/CAR-T recipients diagnosed with COVID-19 at Memorial Sloan Kettering Cancer Center between July 2021 and July 2022. We identified 353 patients (172 autologous HCT recipients [49%], 152 allogeneic HCT recipients [43%], and 29 CAR-T recipients [8%]), with a median time from HCT/CAR-T to SARS-CoV-2 infection of 1010 days (interquartile range, 300 to 2046 days). Forty-one patients (12%) were diagnosed with COVID-19 during the delta wave, and 312 patients (88%) were diagnosed during the Omicron wave. Risk factors associated with increased odds of COVID-19-related hospitalization were the presence of 2 or more comorbidities (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.4 to 10.7; P < .001), CAR-T therapy compared to allogeneic HCT (OR, 7.7; 95% CI, 3.0 to 20.0; P < .001), hypogammaglobulinemia (OR, 2.71; 95% CI, 1.06 to 6.40; P = .027), and age at COVID-19 diagnosis (OR, 1.03; 95% CI, 1.0 to 1.05; P = .04). In contrast, infection during the Omicron variant BA5/BA4-dominant period compared to variant BA1 (OR, .21; 95% CI, .03 to .73; P = .037) and more than 3 years from HCT/CAR-T therapy to COVID-19 diagnosis compared to early infection at <100 days (OR, .31; 95% CI, .12 to .79; P = .011) were associated with a decreased odds for hospitalization. The OS at 12 months from COVID-19 diagnosis was 89% (95% CI, 84% to 94%), with 6 of 26 deaths attributable to COVID-19. Patients with the ancestral strain of SAR-CoV-2 had a lower OS at 12 months, with 73% (95% CI, 62% to 84%) versus 89% (95% CI, 84% to 94%; P < .001) in the Omicron cohort. Specific COVID-19 treatment was administered in 62% of patients, and 84% were vaccinated with mRNA COVID-19 vaccines. Vaccinated patients had significantly better OS than unvaccinated patients (90% [95% CI, 86% to 95%] versus 82% [95% CI, 72% to 94%] at 12 months; P = .003). No significant difference in OS was observed in patients infected with the Omicron and those infected with the Delta variant (P = .4) or treated with specific COVID-19 treatments compared with those not treated (P = .2). We observed higher OS in HCT and CAR-T recipients infected with the Omicron variants compared to those infected with the ancestral strain of SARS-CoV2. The use of COVID-19 antivirals, mAbs, and vaccines might have contributed to the improved outcomes.

Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting.

Immunoglobulin heavy chain variable ( IGHV ) region mutations, TP53 mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify IGHV mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, p < 0.0001), and shorter OS (112 vs. 246 months, p < 0.0001) than the mutated CLL. IGHV3 was the most frequently used IGHV family (46%), followed by IGHV1 (30%) and IGHV4 (16%). IGHV5-51 and IGHV1-69 subfamilies were associated with poor prognosis, while IGHV4 and IGHV2 showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, IGHV2 gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, IGHV and TP53 mutations, IGHV gene families, and CK information could help clinicians in the decision-making process.

Comparing R-Bendamustine vs. R-CHOP Plus Maintenance Therapy as First-Line Systemic Treatment in Follicular Lymphoma: A Multicenter Retrospective GELTAMO Study.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Thrombotic risk and features of patients with inferior vena cava agenesis: a multicentre, retrospective, observational study.

BACKGROUND: Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA. METHODS: In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing. FINDINGS: We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p<0·0001). Analysis of 126 patients with venous thrombosis pooled from cohorts A and B showed early-onset (median age 34·6 years, IQR 23·3-54·3) and recurrent events (50 [40%] of 126 patients). Patients with extrahepatic IVCA had greater proportions of lower-limb venous thrombosis (95 [87%] of 109 vs nine [53%] of 17, p=0·0010) and recurrence (48 [44%] of 109 vs two [12%] of 17, p=0·015), but lower rates of pulmonary embolism (10 [10%] of 99 vs four [33%] of 12, p=0·044) than did patients with hepatic IVCA. 77 (63%) of 122 patients with thrombosis underwent indefinite anticoagulation. 32 (29%) of 111 patients (29 [34%] of 86 with thrombosis) had coexisting thrombophilias. The recurrence risk was lower for patients receiving indefinite anticoagulation (adjusted odds ratio 0·24, 95% CI 0·08-0·61; p=0·010), and greater for thrombophilias (3·19, 1·09-9·32; p=0·034). INTERPRETATION: This evaluation of a large patient cohort demonstrates the high thrombotic burden of IVCA. We have identified two distinct forms of IVCA, hepatic and extrahepatic, suggesting different underlying mechanisms. Beyond clinical characterisation, we draw attention to this orphan disease and highlight the need for its study and improved care. FUNDING: Spanish Society of Thrombosis and Haemostasis, Instituto de Salud Carlos III, FEDER, Fundación Séneca.

Mixed monolayer of DPPC and lysine-based cationic surfactants: an investigation into the antimicrobial activity.

In this paper, we report studies which aim to elucidate the mechanisms involved in the antimicrobial activity of three cationic lysine-based surfactants: LLM, LALM, and C6 (LL)2. To this end, a simple membrane model (i.e., 1,2-dipalmitoyl-sn-phosphatidylcholine, DPPC) was used to explore the monolayer properties at the air/liquid interface. Compression π-A isotherms of mixtures of DPPC/lysine surfactants at different pH showed an expansion of the DPPC monolayer, suggesting cationic lysine surfactant/DPPC interactions, which strongly depend on surfactant structure and hydrophobic interactions. Antimicrobial activity of the three surfactants has also been assessed with transmission electron microscopy, observing the effects on Staphylococcus aureus and Escherichia coli . The three surfactants caused various kinds of damage to the bacteria tested, such as structural alterations, leakage of internal material, and cell destruction.

A pilot screening for cognitive impairment through voice technology (WAY2AGE).

Voice technology has grown exponentially, offering an opportunity to different fields, such as the health area. Considering that language can be a sign of cognitive impairment and most screening tools are based on speech measures, these devices are of interest. The aim of this work was to examine a screening tool for Mild Cognitive Impairment (MCI) through voice technology. For this reason, the WAY2AGE voice Bot was tested across Mini-Mental (MMSE) scores. The main results depict a strong relationship between MMSE and WAY2AGE scores, as well as a good AUC value to discriminate between no cognitive impairment (NCI) and MCI groups. However, a relationship between age and WAY2AGE scores, but not between age and MMSE scores, was found. This would indicate that, even if WAY2AGE seems sensitive to detect MCI, the voice tool is age-sensitive and not as robust as the traditional MMSE scale. Future lines of research should look more deeply into parameters that distinguish developmental changes. As a screening tool, these results are of interest for the health area and for at-risk older adults.

Psychometric Properties of the Subjective Cognitive Decline Questionnaire (SCD-Q) and Its Invariance across Age Groups.

Considering that a good sense of subjective cognitive decline seems to be crucial to prevent decline before clinical impairment, the interest in examining tools on this front were raised in the last decade. The aim of the present study is to examine the psychometric properties of the Subjective Cognitive Decline Questionnaire (SCD-Q) across age in its Spanish adaptation. It should be noted that two constructs were proposed in this context: mnestic processes and executive function factors. For this reason, a sample of 750 individuals aged from 18 to 82 years participated in the study. They were divided into three different groups: young, middle, and older adults. A confirmatory factor analysis (CFA) and invariance analysis were carried out. Moreover, a logistic regression was employed to address the role of age. The results support a good goodness of fit for both uni- and bifactorial models. The invariance analysis reached the structural covariances levels. Last, age did not predict the recognition of cognitive decline in the last two years, while the SCD-Q bifactorial model did. These results are of interest both on a theoretical level, to provide more information on models of cognitive impairment, and on a practical level, for screening.

Evaluation of minimal residual disease by real-time quantitative PCR of Wilms' tumor 1 expression in patients with acute myelogenous leukemia after allogeneic stem cell transplantation: correlation with flow cytometry and chimerism.

Relapse remains the main cause of treatment failure in patients with acute myelogenous leukemia (AML) after allogeneic hemopoietic stem cell transplantation (SCT). The Wilms' tumor 1 gene (WT1) is reportedly overexpressed in >90% of patients with AML and thus can be useful for minimal residual disease (MRD) monitoring. The aim of this study was to evaluate the usefulness of WT1 expression as a relapse predictor marker in patients with AML after SCT and compare it with flow cytometry (FC) and chimerism studies. WT1 expression was assessed retrospectively using quantitative RT-PCR in bone marrow and peripheral blood from 21 patients. Patients were classified according to WT1 dynamics posttransplantation. Eleven of the 21 patients had low and stable WT1 levels. All of these 11 patients showed complete chimerism and negative MRD by FC and remained in complete remission with a median follow-up of 27 months (range, 18-98 months). In contrast, 10 of 21 patients showed WT1 overexpression after SCT, and 9 of these 10 patients relapsed. The incidence of relapse differed significantly between the 2 groups of patients according to WT1 expression post-SCT (P = .00003). Relapse in the 9 patients occurred at a median of 314 days (range, 50-560 days). Interestingly, in these patients, relapse was first predicted by WT1 (with negative FC and complete chimerism) in 7 patients. WT1 overexpression was correlated with disease burden in patients with AML before and after allogeneic SCT. In patients who relapsed, both medullary and extramedullary relapse were better anticipated by WT1 overexpression compared with FC and chimerism.