Intracranial thrombus composition is associated with occlusion location and endovascular treatment outcomes: results from ITACAT multicenter study.

BACKGROUND: The impact of thrombolytics directed towards different thrombus components regarding site of occlusion in combination with mechanical thrombectomy (MT) to achieve endovascular complete recanalization is unclear. METHODS: Retrospective analysis of a prospective database in two stroke centers. Intracranial thrombi retrieved by MT were analyzed using hematoxylin-eosin staining for fibrin and red blood cell proportions, and CD61 immunostaining for platelets proportion in thrombus (PLTPT) assessment. Thrombi composition, baseline variables, etiology, treatment features and occlusion location were analyzed. RESULTS: Overall, 221 patients completed the per protocol analysis and 110 cases achieved a final expanded Thrombolysis in Cerebral Infarction (eTICI) 3 (49%) of which 70 were MT (32%) by first pass effect (FPE). Thrombi from medium distal vessel occlusions had higher PLTPT compared with thrombi from proximal large vessel occlusions (68% vs 61%, P=0.026). In particular, middle cerebral artery M2-M3 segment thrombi had the highest PLTPT (70%), and basilar artery thrombi the lowest PLTPT (41%). After logistic regression analysis adjusted for occlusion location and intravenous fibrinolysis, lower baseline National Institutes of Health Stroke Scale score (adjusted OR (aOR) 0.95, 95% CI 0.913 to 0.998) and PLTPT (aOR 0.97, 95% CI 0.963 to 0.993) were independently associated with FPE. Fewer MT passes (aOR 0.67, 95% CI 0.538 to 0.842) and platelet poor thrombus (<62% PLTPT; aOR 2.39, 95% CI 1.288 to 4.440) were independently associated with final eTICI 3. CONCLUSIONS: Occlusion location might be a surrogate parameter for thrombus composition. Platelet poor clots and fewer MT passes were independently associated with complete endovascular recanalization. Clinical trials testing the benefits of combining selective intra-arterial platelet antagonists with MT to improve endovascular outcomes are warranted.

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.

Monocyte-to-Lymphocyte Ratio in Clot Analysis as a Marker of Cardioembolic Stroke Etiology.

The aim of the study was to find markers of high-risk cardioembolic etiology (HRCE) in patients with cryptogenic strokes (CS) through the analysis of intracranial clot by flow cytometry (FC). A prospective single-center study was designed including patients with large vessel occlusion strokes. The percentage of granulocytes, monocytes, lymphocytes, and monocyte-to-lymphocyte ratio (MLr) were analyzed in clots extracted after endovascular treatment (EVT) and in peripheral blood. Large arterial atherosclerosis (LAA) strokes and high-risk cardioembolic (HRCE) strokes were matched by demographics and acute reperfusion treatment data to obtain FC predictors for HRCE. Multilevel decision tree with boosting random forest classifiers was performed with each feature importance for HRCE diagnosis among CS. We tested the validity of the best FC predictor in a cohort of CS that underwent extensive diagnostic workup. Among 211 patients, 178 cases underwent per-protocol workup. The percentage of monocytes (OR 1.06, 95% CI 1.01-1.11) and MLr (OR 1.83, 95% CI 1.12-2.98) independently predicted HRCE diagnosis when LAA clots (n = 28) were matched with HRCE clots (n = 28). Among CS (n = 82), MLr was the feature with the highest weighted importance in the multilevel decision tree as a predictor for HRCE. MLr cutoff point of 1.59 yield sensitivity of 91.23%, specificity of 44%, positive predictive value of 78.79%, and negative predictive value of 68.75 for HRCE diagnosis among CS. MLr ≥ 1.6 in clot analysis predicted HRCE diagnosis (OR, 6.63, 95% CI 1.85-23.71) in a multivariate model adjusted for age. Clot analysis by FC revealed high levels of monocyte-to-lymphocyte ratio as an independent marker of cardioembolic etiology in cryptogenic strokes.

Is acute lymphoblastic leukemia with mature B-cell phenotype and KMT2A rearrangements a new entity? A systematic review and meta-analysis.

The association between mature B-cell phenotype and KMT2A rearrangements in acute lymphoblastic leukemia is a very rare finding. It identifies a group of patients with similar clinical and biological characteristics that clearly differs from the entity B-cell lymphoblastic leukemia/lymphoma with t(v;11q23)/KMT2A-rearranged, which typically presents an immature pro B-cell phenotype. We describe the clinical-biological characteristics and disease outcome of three pediatric ALL patients with these features treated at our institution, and review 28 cases described in the literature. Most cases occur in children under 2 years-old, presenting a mature B-cell phenotype that uniformly expresses cytoplasmic and surface IgM with lambda light chain restriction, with heterogeneous co-expression of immaturity antigens. Patients do not have MYC rearrangements and all show KMT2A abnormalities, with 76% presenting t(9;11)(p21;q23)/MLLT3-KMT2A. These patients have an unfavorable clinical outcome and a 48% relapse rate. In-depth knowledge of this disease entity is needed to improve outcome.

Utility of lymphocyte phenotype profile to differentiate primary Sjögren's syndrome from sicca syndrome.

OBJECTIVE: To assess the potential diagnostic utility of advanced lymphocyte profiling to differentiate between primary Sjögren's Syndrome (pSS) and non-Sjögren Sicca syndrome. METHODS: Distribution of peripheral lymphocyte subpopulations was analysed by flow cytometry in 68 patients with pSS, 26 patients with sicca syndrome and 23 healthy controls. The ability to discriminate between pSS and sicca syndrome was analysed using the area under the curve (AUC) of the receiver operating characteristic curve of the different lymphocyte subsets. RESULTS: The ratio between naïve/memory B cell proportions showed an AUC of 0.742 to differentiate pSS and sicca syndrome, with a sensitivity of 76.6% and a specificity of 72% for a cut-off value of 3.4. The ratio of non-switched memory B cells to activated CD4+ T cells percentage (BNSM/CD4ACT) presented the highest AUC (0.840) with a sensitivity of 83.3% and specificity of 81.7% for a cut-off value <4.1. To differentiate seronegative pSS patients from sicca patients, the BNSM/CD4ACT ratio exhibited an AUC of 0.742 (sensitivity 75%, specificity 66.7%, cut-off value <4.4), and the number of naïve CD4 T cells had an AUC of 0.821 (sensitivity 76.9%, specificity 88.9%, cut-off value <312/mm3). CONCLUSION: Patients with pSS show a profound imbalance in the distribution of circulating T and B lymphocyte subsets. The ratio BNSM/CD4ACT is useful to discriminate between pSS and sicca syndrome.

Informe de caso: tolerancia e hiperalgesia por opioides posterior a traumatismo abdominal / Case report: Opioid tolerance and hyperalgesia after abdominal injury

Introduction: Opioid tolerance and hyperalgesia are two occurrences that can pose great difficulty in managing both acute and chronic pain. The diagnostic and therapeutic approach requires profound knowledge of opioid pharmacology and related issues such as addiction and pseudoaddiction. This paper presents the case of a patient with multiple interventions, non-functional gastrointestinal tract, increasing uncontrolled pain, exposed to high-dose opioids. Opioid tolerance and hyperalgesia were diagnosed. An opioid rotation regimen was initiated followed by ketamine and dexmedetomidine infusions until a response was finally obtained. Conclusion: Opioid tolerance and hyperalgesia are very difficult to manage and treatment is very complex in the absence of a functional gastrointestinal tract. Opioid rotation, ketamine and dexmedetomidine were the mainstays of treatment in this case.

Introducción: a tolerancia e hiperalgesia por opioides son dos fenómenos que pueden generar grandes dificultades en el manejo del dolor tanto agudo como crónico, el enfoque diagnóstico y terapéutico exige gran conocimiento de la farmacología de los opioides y de fenómenos relacionados como adicción y pseudoadicción. En el presente artículo se expone un caso de una paciente poli intervenida, con tracto gastrointestinal no funcional, con dolor de aumento progresivo, no controlado y expuesta a altas dosis de opioides. Se diagnosticó tolerancia e hiperalgesia por opioides, se inició esquema de rotación de opioides y posteriormente infusiones de ketamina y dexmedetomidina con lo que finalmente se obtuvo respuesta. Conclusión: la tolerancia e hiperalgesia por opioides son dos fenómenos cuyo enfoque terapéutico es supremamente complejo en ausencia de tracto gastrointestinal funcional. La rotación de los opioides, la ketamina y la dexmedetomidina fueron pilares del tratamiento en este caso.

Informe de caso: Anestesia subdural en la paciente obstétrica / Case report: Subdural anesthesia in the obstetric patient

Introduction: Subdural anesthesia is a relatively frequent complication though seldom recognized. It has a broad spectrum of presentations ranging from an unexpectedly high sensory block with limited motor block, to substantial hemodynamic and respiratory involvement. Case presentation: A 22-year old woman undergoing cesarean section under epidural anesthesia with evidence of long-lasting higher than expected sensory block and respiratory distress. Conclusion: Neuraxial anesthesia comprises a number of versatile and safe techniques, though not exempt from complications including subdural anesthesia. We should be aware of this possibility in our clinical practice, know the risk factors and the diagnostic criteria.

Introducción: La anestesia subdural es una complicación de la anestesia neuroaxial relativamente frecuente pero poco reconocida, tiene un espectro de presentación bastante amplio que va desde un bloqueo sensitivo inesperadamente alto con poco bloqueo motor, hasta compromiso hemodinámico y respiratorio importante. Presentación del caso: Mujer de 22 años que es llevada a cesárea con anestesia epidural, con evidencia de bloqueo sensitivo más alto de lo esperado, de larga duración y dificultad respiratoria. Conclusión: La anestesia neuroaxial es un conjunto de técnicas versátiles y seguras, aunque no exentas de complicaciones como lo es la anestesia subdural. En la práctica clínica debemos estar atentos a esta posibilidad, conocer los factores de riesgo y los criterios diagnósticos.