Limited vertical tarsal resection in a case of basal cell carcinoma of the lower eyelid.

We present the clinical case of a 71-year-old woman with a history of multiple basal cell carcinomas (BCC) who presented a nodular lesion in practically the entire extension of the free edge of the lower eyelid. The lesion was approached by excision of the palpebral margin with limited vertical resection of the tarsus and Tripier flap with a correct aesthetic and functional result, free histological margins and no recurrence in a 12-month follow-up.

CAR T in patients with large B-cell lymphoma not fit for autologous transplant.

Large B-cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT. Unfit patients were more likely to receive tisa-cel versus axi-cel (52% vs. 48%) compared to 20% versus 80% in ASCT-fit patients; p < 0.0001. The drop-out rate from approval to infusion was significantly higher in the ASCT-unfit group (34.6% vs. 23.5%; p = 0.042). Among infused patients, response rate, progression-free and overall survival were similar in both cohorts. CAR T was well-tolerated in ASCT-unfit patients with an incidence of grade ≥3 cytokine release syndrome and neurotoxicity of 2% and 11%, respectively. Results from this multicentre real-world cohort demonstrate that CD19 CAR T can be safely delivered in carefully selected older patients and patients with comorbidities who are not deemed suitable for transplant.

Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis.

Acute B-cell lymphoblastic leukemia (B-ALL) results from oligo-clonal evolution of B-cell progenitors endowed with initiating and propagating leukemia properties. The activation of both the Rac guanine nucleotide exchange factor (Rac GEF) Vav3 and Rac GTPases is required for leukemogenesis mediated by the oncogenic fusion protein BCR-ABL. Vav3 expression becomes predominantly nuclear upon expression of BCR-ABL signature. In the nucleus, Vav3 interacts with BCR-ABL, Rac, and the polycomb repression complex (PRC) proteins Bmi1, Ring1b and Ezh2. The GEF activity of Vav3 is required for the proliferation, Bmi1-dependent B-cell progenitor self-renewal, nuclear Rac activation, protein interaction with Bmi1, mono-ubiquitination of H2A(K119) (H2AK119Ub) and repression of PRC-1 (PRC1) downstream target loci, of leukemic B-cell progenitors. Vav3 deficiency results in de-repression of negative regulators of cell proliferation and repression of oncogenic transcriptional factors. Mechanistically, we show that Vav3 prevents the Phlpp2-sensitive and Akt (S473)-dependent phosphorylation of Bmi1 on the regulatory residue S314 that, in turn, promotes the transcriptional factor reprogramming of leukemic B-cell progenitors. These results highlight the importance of non-canonical nuclear Rho GTPase signaling in leukemogenesis.

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

Validation of the Spanish-language version of the Montreal Cognitive Assessment as a screening test for cognitive impairment in multiple sclerosis.

BACKGROUND: The neuropsychological batteries traditionally used for the assessment of cognitive impairment (CI) in patients with multiple sclerosis are complex tests requiring a long time to administer. Simpler tests are needed to detect cognitive impairment in daily clinical practice. OBJECTIVE: We aimed to evaluate the diagnostic validity and reliability of the Montreal Cognitive Assessment (MoCA) test as a screening tool for CI in patients with multiple sclerosis, as compared against the Brief Neuropsychological Battery. MATERIAL AND METHODS: We recruited 52 patients with multiple sclerosis (61.5% women; mean age [standard deviation]: 41.7 [11.5] years). We analysed the reliability (internal consistency, interobserver reliability, and test-retest reliability), construct validity (factor analysis, Pearson correlation coefficient, and coefficient of determination), and criterion validity (ROC curve, sensitivity, specificity, total agreement, positive and negative predictive values, positive and negative likelihood ratios, and Fagan nomogram) of the MoCA test in this population. RESULTS: The prevalence of CI was 21.2% according to findings from the Brief Neuropsychological Battery, and 25% according to the MoCA test. The MoCA test showed good internal consistency (Cronbach alpha, 0.822) and interobserver and test-retest reliability (intraclass correlation coefficient 0.80 and 0.96, respectively). The correlation coefficient between total Brief Neuropsychological Battery and MoCA test scores was 0.82. The optimal cut-off point on the ROC curve was 25-26, yielding 91% sensitivity and 93% specificity. CONCLUSION: The MoCA test is a valid and reliable tool for screening for CI in patients with multiple sclerosis.

Diagnostic value of quantitative SPECT/CT in assessing active sacroiliitis in patients with axial spondylarthritis and/or inflammatory low back pain.

BACKGROUND: The diagnostic accuracy of bone scintigraphy (BS) increases with SPECT/CT imaging. It would therefore be appropriate to reassess the diagnostic utility of scintigraphy in sacroiliitis with axial spondyloarthritis (SpA). The aim of this study was to compare the diagnostic performance of MRI, SPECT/CT and a combination of both techniques in sacro-iliitis, and to evaluate the correlation between quantitative SPECT/CT indices and quantitative MRI inflammatory lesion scores. METHODS: Thirty-one patients with active SpA and 22 patients with inflammatory low back pain underwent MRI and SPECT/CT of the sacroiliac joints. The diagnostic accuracy of both techniques was calculated using clinical diagnosis as the gold standard. The correlation between MRI and SPECT/CT was calculated by comparing the SPECT/CT activity indices and the Berlin/SPARCC scoring systems for MRI. RESULTS: The sensitivity and specificity values in quantitative SPECT/CT, taking the sacroiliac/promontory ratio of >1.36 as the cut-off value, were close to those from MRI published in the literature. The combination of both techniques increased sensitivity while maintaining high specificity. There was a moderate correlation between SPECT/CT and MRI total scores. This correlation was improved by using solely the MRI inflammation scores. CONCLUSION: Quantitative SPECT/CT showed better diagnostic accuracy than planar scintigraphy and showed a moderate correlation with MRI scores in active sacroiliitis. The combination of both tests increased the diagnostic accuracy. Quanti-tative SPECT/CT could play a relevant role in the diagnosis of active sacroiliitis in patients with high a suspicion of SpA and a negative/inconclusive MRI test or in patients with whom MRI studies cannot be carried out.

Document of revision and updating of medication overuse headache (MOH). / Documento de revisión y actualización de la cefalea por uso excesivo de medicación (CUEM).

INTRODUCTION: Medication overuse headache is a secondary headache in which the regular or frequent use of analgesics can increase the frequency of the episodes, causing the transition from episodic to chronic headache. The prevalence of medication overuse headache is approximately 1-2%, with higher rates among women aged 30-50 years and with comorbid psychiatric disorders such as depression or anxiety, or other chronic pain disorders. It is important to be familiar with the management of this disease. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a consensus document addressing this disorder. DEVELOPMENT: These guidelines were prepared by a group of neurologists specialising in headache after a systematic literature review and provides consensus recommendations on the proper management and treatment of medication overuse headache. The treatment of medication overuse headache is often complex, and is based on 4 fundamental pillars: education and information about the condition, preventive treatment, discontinuation of the drug being overused, and treatment for withdrawal symptoms. Follow-up of patients at risk of recurrence is important. CONCLUSIONS: We hope that this document will be useful in daily clinical practice and that it will update and improve understanding of medication overuse headache management.

Small bowel obstruction caused by pericaecal hernia resolved with a laparoscopic approach.

Small bowel obstruction from internal hernias is a familiar pathology for the surgeon, with an incidence of 0.5-5.8%. However, pericaecal hernia is a very uncommon type of internal hernia. Diagnosis and early treatment are essential to avoid strangulation and necrosis of the incarcerated small bowel. We report a case of an 84-year-old woman with no previous history of abdominal surgery who came to our hospital having endured 6 hours of abdominal pain and vomiting. Following physical examination and computed tomography, a diagnosis of small bowel obstruction caused by pericaecal hernia was made and emergency surgery was performed. The hernia was successfully reduced with a laparoscopic approach. Although pericaecal hernia is a rare disease, surgeons should bear it in mind as a differential diagnosis in small bowel obstruction.

Pregnancy success rate and response to heparins and/or aspirin differ in women with antiphospholipid antibodies according to their Global AntiphosPholipid Syndrome Score.

BACKGROUND: The current treatment to prevent pregnancy morbidity (PM) associated with antiphospholipid antibodies (aPL) is based on the use of low dose aspirin and low molecular weight heparin (henceforth defined as standard of care (SoC) treatment). Despite the SoC, up to 30% of women with aPL continue to have pregnancy complications. The global antiphospholipid syndrome (APS) score (GAPSS) is a tool to quantify the risk for the aPL-related clinical manifestations. In this study, we investigated the individual clinical response to SoC in women with aPL after stratifying them according to their GAPSS. METHODS: One-hundred-fourty-three women (352 pregnancies) with aPL ever pregnant treated with SoC therapy were included. The patients GAPSS was then grouped according to the patients' GAPSS into low risk (< 6), medium risk (6-11), and high risk (≥12). RESULTS: The live birth rate was 70.5% (248 out of the 352 pregnancies), 45 patients (31%) experienced at least one event of PM, defined as early or late. Patients were stratified according to GAPSS values, in order to identify a low risk group (GAPSS <6, n = 72), a medium risk group (GAPSS 6-11, n = 66) and a high risk group (GAPSS ≥12, n = 5). When considering patients who ever experienced any PM while treated with SoC, all patients in the high risk group experienced PM, while patients in the medium group had a significant higher rate of PM when compared to the low risk group [29 (43.9%) patients V.s. 11 (15.3%), respectively; p < 0.001]. When analysing the number of pregnancies in the three groups, patients in the high risk group had significantly lower live birth rates, when compared to the other groups [11 (40.7%) live births vs. 100 (62.1%) and 137 (82.5%), respectively; p < 0.05]. Furthermore, patients with medium risk group also had significantly lower live birth rates, when compared to the lower risk group (p < 0.001). CONCLUSIONS: GAPSS might be a valuable tool for to identify patients with a higher likelihood of response to SoC.

Validation of the Spanish-language version of the Montreal Cognitive Assessment as a screening test for cognitive impairment in multiple sclerosis. / Validación de la versión española de la Escala Cognitiva de Montreal (MoCA) como herramienta de cribado de deterioro cognitivo asociado a la esclerosis múltiple.

INTRODUCTION: The neuropsychological batteries traditionally used for the assessment of cognitive impairment (CI) in patients with multiple sclerosis are complex tests requiring a long time to administer. Simpler tests are needed to detect cognitive impairment in daily clinical practice. OBJECTIVE: We aimed to evaluate the diagnostic validity and reliability of the Montreal Cognitive Assessment (MoCA) test as a screening tool for CI in patients with multiple sclerosis, as compared against the Brief Neuropsychological Battery. MATERIAL AND METHODS: We recruited 52 patients with multiple sclerosis (61.5% women; mean age [standard deviation]: 41.7 [11.5] years). We analysed the reliability (internal consistency, interobserver reliability, and test-retest reliability), construct validity (factor analysis, Pearson correlation coefficient, and coefficient of determination), and criterion validity (ROC curve, sensitivity, specificity, total agreement, positive and negative predictive values, positive and negative likelihood ratios, and Fagan nomogram) of the MoCA test in this population. RESULTS: The prevalence of CI was 21.2% according to findings from the Brief Neuropsychological Battery, and 25% according to the MoCA test. The MoCA test showed good internal consistency (Cronbach alpha, 0.822) and interobserver and test-retest reliability (intraclass correlation coefficient 0.80 and 0.96, respectively). The correlation coefficient between total Brief Neuropsychological Battery and MoCA test scores was 0.82. The optimal cut-off point on the ROC curve was 25-26, yielding 91% sensitivity and 93% specificity. CONCLUSION: The MoCA test is a valid and reliable tool for screening for CI in patients with multiple sclerosis.