Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).

A longitudinal prospective study of active tuberculosis in a Western Europe setting: insights and findings.

PURPOSE: This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. METHODS: People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. RESULTS: The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. CONCLUSIONS: IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB.

Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.

RATIONALE: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. AIMS: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. METHODS AND DESIGN: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. STUDY OUTCOMES: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. DISCUSSION: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.

Characterization of respiratory bacterial co-infection and assessment of empirical antibiotic treatment in patients with COVID-19 at hospital admission.

Accurate characterization of respiratory bacterial co-infection is critical for guiding empirical antibiotic treatment for hospitalised patients with coronavirus disease 2019 (COVID-19). We retrospectively assessed the clinical and analytical predictors of respiratory bacterial co-infection and described the empirical use of antibiotics in COVID-19 hospitalised patients. Respiratory bacterial co-infection was documented in 6.9% (80/1157) of the patients. The predominant bacteria isolates were Haemophilus influenzae, followed by Streptococcus pneumoniae and Pseudomonas aeruginosa. Respiratory bacterial co-infection was associated with having had a positive culture for a respiratory pathogen in the last year (OR = 25.89), dyslipidaemia (OR = 2.52), heart failure (OR = 7.68), ferritin levels < 402 ng/mL (OR = 2.28), leukocyte count > 8.7 × 109/L (OR = 2.4), and patients with chronic obstructive pulmonary disease treated with inhaled corticosteroids (OR = 12.94). Empirical antibiotic treatment was administered in 42.33% of patients, although it declined across the distinct study periods (p < 0.001). Patients admitted to intensive care units harbouring co-infection exhibited worse outcomes and more bacterial secondary infections. In conclusion, respiratory bacterial co-infection prevalence was low, although it could lead to unfavourable outcomes. Moreover, the percentage of empirical antibiotic treatment remained high. The study's findings allowed the identification of several predictors for respiratory bacterial co-infection and could help implement adequate antibiotic stewardship measures.

The reproductive status determines tolerance and resistance to Mycobacterium marinum in Drosophila melanogaster.

Sex and reproductive status of the host have a major impact on the immune response against infection. Our aim was to understand their impact on host tolerance or resistance in the systemic Mycobacterium marinum infection of Drosophila melanogaster. We measured host survival and bacillary load at time of death, as well as expression by quantitative real-time polymerase chain reaction of immune genes (diptericin and drosomycin). We also assessed the impact of metabolic and hormonal regulation in the protection against infection by measuring expression of upd3, impl2 and ecR. Our data showed increased resistance in actively mating flies and in mated females, while reducing their tolerance to infection. Data suggests that Toll and immune deficiency (Imd) pathways determine tolerance and resistance, respectively, while higher basal levels of ecR favours the stimulation of the Imd pathway. A dual role has been found for upd3 expression, linked to increased/decreased mycobacterial load at the beginning and later in infection, respectively. Finally, impl2 expression has been related to increased resistance in non-actively mating males. These results allow further assessment on the differences between sexes and highlights the role of the reproductive status in D. melanogaster to face infections, demonstrating their importance to determine resistance and tolerance against M. marinum infection.

Self-sampling monkeypox virus testing in high-risk populations, asymptomatic or with unrecognized Mpox, in Spain.

The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess prevalence of MPXV in high-risk populations of GBMSM, trans women (TW) and non-binary people without symptoms or with unrecognized monkeypox (Mpox) symptoms, using a self-sampling strategy. Anal and pharyngeal swabs are tested by MPXV real-time PCR and positive samples are tested for cytopathic effect (CPE) in cell culture. 113 individuals participated in the study, 89 (78.76%) were cis men, 17 (15.04%) were TW. The median age was 35.0 years (IQR: 30.0-43.0), 96 (85.02%) individuals were gay or bisexual and 72 (63.72%) were migrants. Seven participants were MPXV positive (6.19% (95% CI: 1.75%-10.64%)). Five tested positive in pharyngeal swabs, one in anal swab and one in both. Six did not present symptoms recognized as MPXV infection. Three samples were positive for CPE, and showed anti-vaccinia pAb staining by FACS and confocal microscopy. This suggests that unrecognized Mpox cases can shed infectious virus. Restricting testing to individuals reporting Mpox symptoms may not be sufficient to contain outbreaks.

Clinical Performance of Lateral Flow Assay for Cryptosporidium spp. Diagnosis.

Cryptosporidium spp. is an apicomplexan protozoan parasite associated with gastroenteritis in humans. In 2018, Spain showed 1511 confirmed cases, with a growing trend since 2014. Despite this fact, Cryptosporidium spp. is not usually routinely examined when a parasitological study is ordered, although accurate diagnosis is fundamental to prevent the spread of the illness. The main objectives of the present work is to demonstrate the circulation and to study the epidemiology of cryptosporidiosis in patients who were being tested for the presence of Cryptosporidium spp. parasites in the faeces in the Metropolitan North Area of Barcelona, Maresme, and Vallés Occidental using a two-step algorithm. The stool samples were analysed using the Cryptosporidium/Giardia spp. immunochromatographic test; the positive samples were visualised under a microscope using auramine staining. The proportion of Cryptosporidium spp. cases was around 2% in the studied patients, with a pronounced seasonal incidence peak in late summer-early autumn. In our cohort, weight loss was the main symptom related to confirmed cases. The mean age of confirmed patients was 19 years old, and they were younger than the unconfirmed group. Cryptosporidium spp. is one of the parasites that currently circulate in many areas in Europe. Prevalence must be taken into account for active searching.

Mycobacterium manresensis induces trained immunity in vitro.

The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days.

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes.

We aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson's r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9-42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment.

Surveillance of Daughter Micronodule Formation Is a Key Factor for Vaccine Evaluation Using Experimental Infection Models of Tuberculosis in Macaques.

Tuberculosis (TB) is still a major worldwide health problem and models using non-human primates (NHP) provide the most relevant approach for vaccine testing. In this study, we analysed CT images collected from cynomolgus and rhesus macaques following exposure to ultra-low dose Mycobacterium tuberculosis (Mtb) aerosols, and monitored them for 16 weeks to evaluate the impact of prior intradermal or inhaled BCG vaccination on the progression of lung disease. All lesions found (2553) were classified according to their size and we subclassified small micronodules (<4.4 mm) as 'isolated', or as 'daughter', when they were in contact with consolidation (described as lesions ≥ 4.5 mm). Our data link the higher capacity to contain Mtb infection in cynomolgus with the reduced incidence of daughter micronodules, thus avoiding the development of consolidated lesions and their consequent enlargement and evolution to cavitation. In the case of rhesus, intradermal vaccination has a higher capacity to reduce the formation of daughter micronodules. This study supports the 'Bubble Model' defined with the C3HBe/FeJ mice and proposes a new method to evaluate outcomes in experimental models of TB in NHP based on CT images, which would fit a future machine learning approach to evaluate new vaccines.

Evolution of quality indicators in acute stroke during the RACECAT Trial: Impact in the general population.

BACKGROUND: Acute ischemic stroke patients not referred directly to a comprehensive stroke center (CSC) have reduced access to endovascular treatment (EVT). The RACECAT trial is a population-based cluster-randomized trial, designed to compare mothership and drip-and-ship strategies in acute ischemic stroke patients outside the catchment area of a CSC. AIMS: To analyze the evolution of performance indicators in the regions that participated in RACECAT. METHODS: This retrospective longitudinal observational study included all stroke alerts evaluated by emergency medical services in Catalonia between February 2016 and February 2020. Cases were classified geographically according to the nearest SC: local SC (Local-SC) and CSC catchment areas. We analyzed the evolution of EVT rates and relevant workflow times in Local-SC versus CSC catchment areas over three study periods: P1 (February 2016 to April 2017: before RACECAT initiation), P2 (May 2017 to September 2018), and P3 (October 2018 to February 2020). RESULTS: We included 20603 stroke alerts, 10,694 (51.9%) of which were activated within Local-SC catchment areas. The proportion of patients receiving EVT within Local-SC catchment areas increased (P1 vs. P3: 7.5% (95% confidence interval (CI), 6.4-8.7) to 22.5% (95% CI, 20.8-24.4) p < 0.001). Inequalities in the odds of receiving EVT were reduced for patients from CSC versus Local-SC catchment areas (P1: odds ratio (OR) 3.9 (95% CI, 3.2-5) vs. P3: OR 1.5 (95% CI, 1.3-1.7) In Local-SC, door-to-image (P1: 24 (interquartile range (IQR) 15-36), P2: 24 (15-35), P3: 21 (13-32) min, p < 0.001) and door-to-needle times (P1: 42 (31-60), P2: 41 (29-58), P3: 35 (25-50) p < 0.001) reduced. Time from Local-SC arrival to groin puncture also decreased over time (P1: 188 [151-229], P2: 190 (157-233), P3: 168 (127-215) min, p < 0.001). CONCLUSION: An increase in EVT rates in Local-SC regions with a significant decrease in workflow times occurred during the period of the RACECAT trial.

Effects of Bihemispheric Transcranial Direct Current Stimulation Combined With Repetitive Peripheral Nerve Stimulation in Acute Stroke Patients.

PURPOSE: Transcranial direct current stimulation (tDCS) can change the excitability of the central nervous system and contribute to motor recovery of stroke patients. The aim of our study was to examine the short- and long-term effects of real versus sham bihemispheric tDCS combined with repetitive peripheral nerve stimulation in patients with acute stroke and a severe motor impairment. METHODS: The study was prospective, randomized, double blind, and placebo controlled. Nineteen acute stroke patients (ischemic and hemorrhagic) with upper limb Fugl-Meyer mean score of <19 were randomized in two groups: one group received five consecutive daily sessions of anodal tDCS over the affected hemisphere and cathodal over unaffected hemisphere combined with repetitive peripheral nerve stimulation and the other received sham tDCS associated to repetitive peripheral nerve stimulation. Clinical and neurophysiological assessment was applied before tDCS, 5 days after tDCS, and 3, 6, and 12 months after tDCS. RESULTS: There were significant time-related changes in both groups of patients in motor evoked potentials, somatosensory evoked potentials, Hmax:Mmax ratio, upper limb Fugl-Meyer scores, and Modified Ashworth scales scores ( P < 0.05). However, no significant differences between groups were present at any time ( P > 0.05). CONCLUSIONS: Bihemispheric tDCS and repetitive peripheral nerve stimulation with the parameters of our study did not add significant short- or long-term clinical improvement or change in neurophysiological data in severe acute stroke patients in comparison to sham stimulation. The severity of motor impairment in stroke patients may influence a possible response to an interventional tDCS treatment.

First pass effect in posterior circulation occlusions: Analysis from the CICAT registry.

BACKGROUND: The first pass effect (FPE) is an independent predictor of functional independence in patients with large vessel occlusion in anterior circulation ischemic strokes. However, whether it predicts outcome in posterior circulation large vessel occlusion (PC-LVO) is uncertain. We aimed to study the frequency, characteristics, and predictors of FPE and its association with clinical outcomes in PC-LVO. METHOD: We performed an analysis from the prospective CICAT Registry. All patients with PC-LVO who underwent endovascular therapy between January 2016 and January 2020 were included. A centrally assessed clinical follow-up was performed at 3 months by blinded investigators. FPE was defined as the achievement of modified Thrombolysis In Cerebral Infarction 3 in a single pass of the endovascular thrombectomy device, and multi-pass effect (MPE) if it was achieved in more than one pass. A multivariable analysis was performed to identify whether FPE is an independent predictor of functional independence defined as a modified Rankin Score of 0-2. RESULTS: We analyzed data from 265 patients in who FPE was achieved in 105 (39.6%). Patients with FPE were more likely to achieve functional independence compared to the non-FPE group (52.4% vs 25.1%, p < .001) and the MPE group (52.4% vs 26.7%, p < .001). FPE was independently associated with functional independence (adjusted odds ratio (aOR): 2.10, 95% confidence interval (CI) 1.01-4.37) but MPE was not (aOR: 0.92, 95% CI 0.40-2.13). Independent predictors of FPE were the use of direct aspiration, embolic mechanism of stroke, and the absence of general anesthesia (GA) use. CONCLUSIONS: FPE is an independent predictor of functional independence in PC-LVO and was associated with a significantly better outcome than MPE.

Viral dynamics in patients with monkeypox infection: a prospective cohort study in Spain.

BACKGROUND: Monkeypox DNA has been detected in skin lesions, saliva, oropharynx, urine, semen, and stool of patients infected during the 2022 clade IIb outbreak; however, the viral dynamics within these compartments remain unknown. We aimed to characterise the viral load kinetics over time in various parts of the body. METHODS: This was an observational, prospective, multicentre study of outpatients diagnosed with monkeypox in two hospitals and two sexual health clinics in Spain between June 28, 2022, and Sept 22, 2022. Men and women aged over 18 years were eligible if they reported having symptom onset within the previous 10 days of presentation, and were ineligible if disease was severe enough to be admitted to hospital. Samples were collected from five body locations (skin lesions, oropharynx, rectum, semen or vagina, and a dried blood spot) at six time points up to 57 days after the screening visit. Samples were analysed by quantitative PCR and a subset by cell culture. The primary endpoint was time from symptom onset to viral DNA clearance. FINDINGS: Overall, 1663 samples were collected from 77 study participants. 75 (97%) participants were men, the median age was 35·0 years (IQR 29·0-46·0), and 39 (51%) participants were living with HIV. The median time from symptom onset to viral clearance was 25 days (95% CI 23-28) in the skin lesions, 16 days (13-19) in the oropharynx, 16 days (13-23) in the rectum, 13 days in semen (9-18), and 1 day in blood (0-5). The time from symptom onset to viral clearance for 90% of cases was 41 days (95% CI 34-47) in skin lesions and 39 days (27-56) in semen. The median viral load in skin lesions was 7·3 log10 copies per mL (IQR 6·5-8·2) at baseline, compared with 4·6 log10 copies per mL (2·9-5·8) in oropharyngeal samples, 5·0 log10 copies per mL (2·9-7·5) in rectal samples, 3·5 log10 copies per mL (2·9-4·7) in semen samples, and 4·0 log10 copies per mL (4·0-4·0) in blood specimens. Replication-competent viruses were isolated in samples with high DNA levels (>6·5 log10 copies per mL). INTERPRETATION: In immunocompetent patients with mild monkeypox disease, PCR data alone would suggest a contact isolation period of 3 to 6 weeks but, based on detection of replication-competent virus, this time could be reduced. Based on findings from this cohort of patients, semen testing and prolonged use of condoms after recovery from monkeypox might not be necessary. FUNDING: University Hospital Germans Trias i Pujol and the YoMeCorono. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Evaluating the Accuracy of Self-Collected Swabs for the Diagnosis of Mpox.

We evaluated the accuracy of patient-collected skin lesions, oropharyngeal, and rectal swabs among 50 individuals enrolled in a study of mpox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing mpox.

Monitoring SARS-CoV-2 variant transitions using differences in diagnostic cycle threshold values of target genes.

Monitoring the emergence of new SARS-CoV-2 variants is important to detect potential risks of increased transmission or disease severity. We investigated the identification of SARS-CoV-2 variants from real-time reverse transcriptase polymerase chain reaction (RT-PCR) routine diagnostics data. Cycle threshold (Ct) values of positive samples were collected from April 2021 to January 2022 in the Northern Metropolitan Area of Barcelona (n = 15,254). Viral lineage identification from whole genome sequencing (WGS) was available for 4618 (30.3%) of these samples. Pairwise differences in the Ct values between gene targets (ΔCt) were analyzed for variants of concern or interest circulating in our area. A specific delay in the Ct of the N-gene compared to the RdRp-gene (ΔCtNR) was observed for Alpha, Delta, Eta and Omicron. Temporal differences in ΔCtNR correlated with the dynamics of viral replacement of Alpha by Delta and of Delta by Omicron according to WGS results. Using ΔCtNR, prediction of new variants of concern at early stages of circulation was achieved with high sensitivity and specificity (91.1% and 97.8% for Delta; 98.5% and 90.8% for Omicron). Thus, tracking population-wide trends in ΔCt values obtained from routine diagnostics testing in combination with WGS could be useful for real-time management and response to local epidemics.

Drosophila melanogaster as a model to study innate immune memory.

Over the last decades, research regarding innate immune responses has gained increasing importance. A growing body of evidence supports the notion that the innate arm of the immune system could show memory traits. Such traits are thought to be conserved throughout evolution and provide a survival advantage. Several models are available to study these mechanisms. Among them, we find the fruit fly, Drosophila melanogaster. This non-mammalian model has been widely used for innate immune research since it naturally lacks an adaptive response. Here, we aim to review the latest advances in the study of the memory mechanisms of the innate immune response using this animal model.

Correlation between Clinical and Immunological Variables and Humoral Response to SARS-CoV-2 Vaccination in Adult Patients with Antibody Deficiency Disorders.

BACKGROUND: Prophylactic vaccination has proven to be the most effective strategy to fight the COVID-19 pandemic. METHODS: This was a prospective observational cohort study involving 30 predominantly antibody deficiency disorders (ADD)-afflicted adult patients on immunoglobulin replacement therapy vaccinated with three doses of the mRNA-1273 COVID-19 vaccine, and 10 healthy controls. Anti-RBD IgG antibodies were determined in plasma samples collected just before the first dose of mRNA-based COVID-19 vaccine and on weeks 4, 8, 24, and 28 following the first vaccination. Patients were categorized based on the levels of anti-RBD antibodies determined on w8 as non-, low-, and responders. Chi-square and Kruskal-Wallis tests were used to see if any variables correlated with humoral response levels. Any adverse effects of the mRNA-based vaccine were also noted. RESULTS: The COVID-19 vaccine was safe and well-tolerated. The humoral response elicited at w8 after vaccination depended on the type of ADD, the type of immunoglobulin deficiency, the presence of granulomatous lymphocytic interstitial lung disease, recent use of immunosuppressive drugs, and the switched memory B cells counts. The third vaccine dose boosted humoral response in previous responders to second dose but seldom in non-responders. CONCLUSIONS: The humoral response of patients with predominant ADD depends mostly on the type of immunodeficiency and on the frequency of B and T cell populations.

Workflows and Outcomes in Patients With Suspected Large Vessel Occlusion Stroke Triaged in Urban and Nonurban Areas.

BACKGROUND: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). METHODS: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. RESULTS: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2-5] versus 3 [1-5], common odds ratio, 1.25 [95% CI, 1.06-1.48]); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08-1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81-1.28]). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16-1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51-0.75]), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25-52]) and thrombectomy(mean difference 66 minutes [95% CI, 37-95]). CONCLUSIONS: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795962.