Bridging Therapy and Occlusion Site Influence Symptomatic Hemorrhage Rate after Thrombectomy: A Daily Practice Study in 623 Stroke Patients.

BACKGROUND: Comparison of symptomatic intracranial hemorrhage (SICH) rates between stroke patients treated with bridging therapy (BT) and primary mechanical thrombectomy (PMT) are scarce and difficult to interpret due to baseline differences between both populations. METHODS: Retrospective analysis of patients with acute ischemic stroke treated with endovascular therapy (BT or PMT) was performed at our center between January 2010 and June 2017. RESULTS: Six hundred twenty-three patients were included. Global SICH rate was 9% overall: 6.8% in the PMT group and 12.6% in the BT group. The following factors significantly associated with SICH after multivariate analysis: MCA occlusion (p: 0.047), stroke of unknown origin (p: 0.025), BT (p: 0.024), and procedural time over 65 min (p: 0.027). The following variables presented a statistically significant higher frequency in patients treated with PMT: atrial fibrillation (p: 0.005), anticoagulant medication (p < 0.001), wake-up strokes (p < 0.001), atherothrombotic etiology (p < 0.05), combined thrombectomy technique (p: 0.008), longer procedural times (p: 0.025), and favorable outcome at 3 months (p: 0.011). The following variables presented a statistically significant higher frequency in patients treated with BT: antiplatelet medication (p: 0.048), MCA occlusions (p: 0.017), cardioembolic etiology (p < 0.05), stent retriever/aspiration technique (p: 0.008), and SICH (p: 0.013). Patients with MCA occlusions had twice the risk of SICH after BT than after PMT (16.4 and 8.6%, p: 0.038). CONCLUSIONS: In this clinical series, the SICH rate was higher in patients treated with BT than in those treated with PMT. Relevant differences in baseline (related to IVT contraindications) were found between both groups. Randomized studies of BT versus PMT in populations with similar baseline characteristics might be of interest.

Are modified Fisher Scale and bleeding pattern helpful predictors of neurological complications in non-aneurysmal subarachnoid hemorrhage?

PURPOSE: Non-aneurysmal subarachnoid hemorrhage (NA-SAH) is a clinical-radiological entity with a different prognosis than aneurysmal SAH (A-SAH). The purpose of this study is to assess the predictive value of the modified Fisher Scale (mFS) for neurological complications in patients with this diagnosis. METHODS: We recruited patients admitted at our hospital services between 2009 and 2017 who were diagnosed with spontaneous SAH, with either perimesencephalic (PM-SAH) or diffuse pattern (D-SAH), an initial negative angio-CT, and at least one digital subtraction angiography of brain vessels discarding underlying brain aneurysms or other vascular malformations. RESULTS: The retrospective observational study included 116 patients. The mean age was 54.4, and the sample included predominantly male subjects (62.9%). Hunt and Hess (HH) scores on admission ranged from 3 to 5 in 18.1% of patients. The prevalence of hydrocephalus requiring ventricular drainage was 18.1%. The prevalence of symptomatic vasospasm was 4.3%. A modified Rankin Scale (mRS) 0-2 at discharge was found in 95.6%. In a multivariate logistic regression for the presence of neurological complications including age, sex, admission HH 3-5 compared with < 3, mFS 4 compared with mFS < 4, D-SAH compared with PM-SAH, and mRS score at discharge of 0-2 compared with > 2, the only significant predictors were mFS 4 compared with mFS < 4 (OR 4.47 (95% CI 1.21, 16.66) p value = 0.03) and D-SAH compared with PM-SAH (OR 7.10 (95% CI 1.24, 40.8) p value = 0.03). CONCLUSION: In patients with NA-SAH, a mFS score of 4 and/or a D-SAH bleeding pattern in non-contrast cranial CT on admission predicted the development of relevant neurological complications.

Neuroendocrine Tumor Heterogeneity Adds Uncertainty to the World Health Organization 2010 Classification: Real-World Data from the Spanish Tumor Registry (R-GETNE).

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki-67 cutoff values in GEP-NENs. SUBJECTS, MATERIALS, AND METHODS: A total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 <2%), G2 (Ki-67 3%-20%), or G3 (Ki-67 >20%). Patients were stratified into five cohorts: NET-G1, NET-G2, NET-G3, NEC-G2, and NEC-G3. RESULTS: Five-year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67 3%-5%], 72% [Ki-67 6%-10%], 52% [Ki-67 11%-20%]) and G3 NENs (5-year survival: 35% [Ki-67 21%-50%], 22% [Ki-67 51%-100%]). Five-year survival was significantly greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3 (43.7% vs. 25.4%). CONCLUSION: Substantial clinical heterogeneity is observed within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index. IMPLICATIONS FOR PRACTICE: Gastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real-world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials.

Mechanical Thrombectomy in Acute Stroke Due to Carotid Occlusion: A Series of 153 Consecutive Patients.

BACKGROUND: Strokes due to carotid artery occlusion (CAO) are associated with bad clinical prognosis and poor response to intravenous thrombolysis. Several studies in the past have shown the benefits of mechanical thrombectomy (MT) and compared bridging therapy (BT) and primary MT (PMT) in large vessel occlusions, but only a few studies have focused on the specific population of CAO and their response to endovascular treatment. METHODS: Retrospective review of patients treated at our center between January 2010 and June 2017 that (1) presented with acute ischemic stroke caused by CAO in the first 4.5 h since symptom onset, and (2) were treated with MT (BT or PMT). Baseline characteristics of the population, comparison between BT and PMT, intrahospital mortality, symptomatic intracranial hemorrhage, and functional outcome were investigated. RESULTS: A total of 153 patients were included. Baseline characteristics: 51.6% were male, and the median age was 71 years. The most frequent risk factor was hypertension (71.9%). The main stroke etiology was atherothrombotic (40.5%). The mean admission National Institute of Health Severity Score (NIHSS) was 19, mean discharge NIHSS was 7. Isolated occlusion of the Extracranial or Intracranial Internal Carotid Artery was the most frequent occlusion location (52.3%). TICI 2b-3 was achieved in 87.6%, intrahospital mortality was 26.8%, symptomatic hemorrhage was 8.5%, and 3 months-modified Rankin Score (mRS) 0-2 was 26.8%. Definitive carotid stenting was needed in 33.3% of the cases. BT versus PMT: Patients treated with PMT presented a higher incidence of atrial fibrillation, anticoagulation, and cardioembolic stroke compared to those treated with BT. No differences in TICI 2b-3, 3 months-mRS or symptomatic hemorrhage were found between both groups. Intrahospital mortality: Poor perfusion-CT mismatch (p = 0.005), isolated Internal carotid artery location (p = 0.024), and symptomatic hemorrhage (p < 0.001) were independent predictors. Symptomatic intracranial hemorrhage: Patients with post-treatment symptomatic hemorrhage had higher intrahospital mortality (p < 0.001) and worse 3 months-mRS (p = 0.033). Functional outcome: Admission NIHSS (p = 0.012) independently predicted 3 months-mRS. CONCLUSIONS: In our population, patients with CAO clinically present with severe strokes. Isolated occlusions of the extra- or intracranial segments of the carotid are more frequent than tandem occlusions. Successful recanalization after thrombectomy is achieved in most of the patients, but association with favorable functional outcome is poor. Clinical evolution is similar in patients treated with PMT and BT. Intracranial symptomatic hemorrhage after treatment is associated with higher intrahospital mortality and worse 3 months-mRS. Poor perfusion-CT mismatch, symptomatic hemorrhage, and isolated CAO are independent predictors of intrahospital mortality. Admission NIHSS is an independent predictor of 3 months-mRS.

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

Prognostic factors and long-term outcome of pancreatic neuroendocrine neoplasms: Ki-67 index shows a greater impact on survival than disease stage. The large experience of the Spanish National Tumor Registry (RGETNE).

INTRODUCTION: Pancreatic neuroendocrine neoplasms (PNENs) are uncommon neoplasms with a wide spectrum of clinical behavior. The objective of this study was to assess in a large cohort of patients the relative impact of prognostic factors on survival. METHODS: From June 2001 through October 2010, 1,271 patients were prospectively registered online (www.getne.org) at the Spanish National Cancer Registry for Gastroenteropancreatic Neuroendocrine Tumors (RGETNE) by participating centers. Clinical and histopathological features were assessed as potential prognostic factors by uni- and multivariate analyses. RESULTS: Of 483 PNENs, 171 (35%) were functional (F) and 312 (65%) non-functional (NF). NF-PNENs were associated with a higher incidence of histological features denoting more aggressive disease, such as poor tumor differentiation, Ki-67 >20%, or vascular invasion (NF- vs. F-PNENs, respectively, p < 0.05). Nevertheless, functionality was not a significant predictor of survival (p = 0.19). Stage at diagnosis, Ki-67 index, tumor differentiation and surgical resection of the primary tumor were all significant prognostic factors in univariate analysis. However, Ki-67 (>20 vs. ≤2%) (hazard ratio (HR) 2.21, p = 0.01) and surgical resection (yes vs. no) (HR 0.92, p = 0.001) were the only independent predictors of survival in multivariate analysis. Among patients who underwent surgery, high Ki-67 index (HR 10.37, p = 0.02) and poor differentiation (HR 8.16, p = 0.03) were the only independent predictors of clinical outcome. CONCLUSION: Ki-67 index and tumor differentiation are key prognostic factors influencing survival of patients with PNENs and, in contrast to what it is observed for other solid malignancies, they seem to have a greater impact on survival than the extent of disease. This should be borne in mind by physicians in order to appropriately tailor therapeutic strategies and surveillance of these patients.

Thrombectomy aspiration post-market study in acute stroke with the Q aspiration catheter: the TAPAS study.

BACKGROUND: The Q Aspiration Catheter (MIVI Neuro) has demonstrated greater aspiration flow rates and ingestion forces compared with conventional catheters in vitro. The safety and performance of the Q Catheter was assessed using a direct aspiration first pass technique in patients with acute ischemic stroke at four neurointerventional centers in Spain. METHODS: We included adult patients who underwent mechanical thrombectomy between March 2019 and March 2020 using the Q Catheter as first-line therapy. Performance endpoints included final successful revascularization of the target vessel (defined as modified thrombolysis in cerebral infarction (mTICI) grade 2B/3), first pass revascularization, and overall Q Catheter revascularization. Safety endpoints were symptomatic intracranial hemorrhage (sICH), embolization to new territory (ENT), and procedural complications. Modified Rankin Scale (mRS) score and all-cause mortality were also assessed. RESULTS: Forty-five subjects were enrolled. The Q Catheter successfully navigated to the lesion in 95.5% (43/45) of patients. Final successful mTICI 2B/3 revascularization was achieved in 93.3% (42/45), first pass mTICI 2B/3 revascularization with the Q Catheter was 55.3% (21/38), and overall with Q Catheter mTICI 2B/3 revascularization was 65.8% (25/38). Favorable clinical outcome of mRS 0-2 was achieved in 55.6% (25/45). There were no cases of ENT. sICH and mortality rates were 2.2% (1/45) and 13.3% (6/45), respectively. CONCLUSION: In this multicenter, observational study, the Q Aspiration Catheter used as first-line therapy demonstrated a good and safe profile in terms of navigation, revascularization, and safety in patients with acute ischemic stroke.

Chronic Treatment with Somatostatin Analogues in Recurrent Type 1 Gastric Neuroendocrine Tumors.

BACKGROUND: Type 1 gastric neuroendocrine tumors (GC-1) represent an uncommon subtype of neoplasms. Endoscopic resection has been proposed as the treatment of choice; active surveillance may be performed in those smaller than 1 cm, while gastric surgery may be performed for those with frequent recurrences. The antiproliferative effect of somatostatin analogues (SSA) is well known, and their action on GC-1s has been postulated as a chronic treatment to reduce recurrence. METHODS: A two-centered, retrospective, observational study that included nine patients (55.6% women) diagnosed with GC-1, receiving long-term treatment with SSA, with a median follow-up from baseline of 22 months, was undertaken. Endoscopic follow-up, extension study, and analytical values of chromogranin A (Cg A) and gastrin were collected. RESULTS: In total, 88.9% of patients presented partial or complete response. Treatment with SSA was the only independent factor with a trend to prevent tumor recurrence (Odds Ratio 0.054; p = 0.005). A nonsignificant tendency toward a decrease in CgA and gastrin was observed; lack of significance was probably related to concomitant treatment with proton pump inhibitors in some patients. CONCLUSIONS: Chronic treatment with SSA is a feasible option for recurrent GC-1s that are difficult to manage using endoscopy or gastrectomy. Randomized clinical trials to provide more scientific evidence are still needed.

Safety and efficacy of tirofiban in acute ischemic stroke due to tandem lesions undergoing mechanical thrombectomy: A multicenter randomized clinical trial (ATILA) protocol.

Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset <24 h) will be randomized (1:1) at MT onset to experimental (intravenous tirofiban) or control group (intravenous aspirin). Intravenous aspirin will be administered at a 500 mg single dose and tirofiban at a 500 µg bolus followed by a 200 µg/h infusion during first 22 h. All patients will be followed up to 3 months. Sample size estimated is 240 patients. Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0-2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596.

Multiple pilomatricomas in association with trisomy 9.

Multiple appearance of pilomatricoma is a rare phenomenon that has been associated with some diseases like Gardner syndrome, myotonic dystrophy, and Rubinstein-Taybi syndrome. We present a case of association of multiple pilomatricoma and trisomy 9, which represents the third published in literature. As a result of the small prevalence of these two entities, we believe they could be related.

Congenital hemangioma: a report of evolution from rapidly involuting to noninvoluting congenital hemangioma with aberrant Mongolian spots.

Congenital hemangiomas are unusual vascular tumors that are fully developed at the time of delivery. We report a case of an infant with an exophytic congenital hemangioma with features of a rapidly involuting hemangioma on the arm which over 3 years decreased in volume but continued to persist with features of a noninvoluting congenital hemangioma. He also had aberrant, persistent Mongolian spots on both legs. To our knowledge, this association has not been reported to date.

Association study of 69 genes in the ret pathway identifies low-penetrance loci in sporadic medullary thyroid carcinoma.

To date, few association studies have been done to better understand the genetic basis for the development of sporadic medullary thyroid carcinoma (sMTC). To identify additional low-penetrance genes, we have done a two-stage case-control study in two European populations using high-throughput genotyping. We selected 417 single nucleotide polymorphisms (SNP) belonging to 69 genes either related to RET signaling pathway/functions or involved in key processes for cancer development. TagSNPs and functional variants were included where possible. These SNPs were initially studied in the largest known series of sMTC cases (n = 266) and controls (n = 422), all of Spanish origin. In stage II, an independent British series of 155 sMTC patients and 531 controls was included to validate the previous results. Associations were assessed by an exhaustive analysis of individual SNPs but also considering gene- and linkage disequilibrium-based haplotypes. This strategy allowed us to identify seven low-penetrance genes, six of them (STAT1, AURKA, BCL2, CDKN2B, CDK6, and COMT) consistently associated with sMTC risk in the two case-control series and a seventh (HRAS) with individual SNPs and haplotypes associated with sMTC in the Spanish data set. The potential role of CDKN2B was confirmed by a functional assay showing a role of a SNP (rs7044859) in the promoter region in altering the binding of the transcription factor HNF1. These results highlight the utility of association studies using homogeneous series of cases for better understanding complex diseases.

Terfenadine-induced apoptosis in human melanoma cells is mediated through Ca2+ homeostasis modulation and tyrosine kinase activity, independently of H1 histamine receptors.

In our previous works, we have demonstrated that terfenadine (TEF) induces DNA damage and apoptosis in human melanoma cell lines. In this present work, we have studied the effect of histamine on viability of A375 human melanoma cells and the cell-signalling pathways through which TEF may induce its apoptotic effect. We have found that exogenous histamine stimulates A375 melanoma cell proliferation in a dose- and time-dependent manner. Moreover, TEF-induced apoptosis seems to occur via other cellular pathways independent of the histamine-signalling system since co-treatment of histamine with TEF did not protect melanoma cells from the cytotoxic effect of TEF, and alpha fluoromethylhistidine did not induce the same cytotoxic effect of TEF. In addition, we have observed that knocking down the H1 histamine receptor (HRH1) by small interference RNA approach protects melanoma cells only slightly from TEF-induced apoptosis. To explore the molecular mechanisms responsible for histamine and TEF effect on the cell growth, we analysed intracellular cyclic nucleotides and Ca(2+) levels. TEF did not modify intracellular levels of cyclic adenosine 3',5'-monophosphate and cyclic guanine 3',5'-monophosphate; however, TEF induced a very sharp and sustained increase in cytosolic Ca(2+) levels in A375 melanoma cells. On the contrary, histamine did not modulate intracellular Ca(2+). TEF-induced Ca(2+) rise and apoptosis appear to be phospholipase C (PLC) dependent since neomycin and U73122, two inhibitors of PLC, abolished cytosolic Ca(2+) increase and protected the cells completely from cell death. Furthermore, inhibition of tyrosine kinase activity by genistein blocked cytosolic Ca(2+) rise and TEF-induced apoptosis. These results suggest that TEF modulates Ca(2+) homeostasis and induces apoptosis through other cellular pathways involving tyrosine kinase activity, independently of HRH1.

Complex signatures of selection for the melanogenic loci TYR, TYRP1 and DCT in humans.

BACKGROUND: The observed correlation between ultraviolet light incidence and skin color, together with the geographical apportionment of skin reflectance among human populations, suggests an adaptive value for the pigmentation of the human skin. We have used Affymetrix U133a v2.0 gene expression microarrays to investigate the expression profiles of a total of 9 melanocyte cell lines (5 from lightly pigmented donors and 4 from darkly pigmented donors) plus their respective unirradiated controls. In order to reveal signatures of selection in loci with a bearing on skin pigmentation in humans, we have resequenced between 4 to 5 kb of the proximal regulatory regions of three of the most differently expressed genes, in the expectation that variation at regulatory regions might account for intraespecific morphological diversity, as suggested elsewhere. RESULTS: Contrary to our expectations, expression profiles did not cluster the cells into unirradiated versus irradiated melanocytes, or into lightly pigmented versus darkly pigmented melanocytes. Instead, expression profiles correlated with the presence of Bovine Pituitary Extract (known to contain alpha-MSH) in the media. This allowed us to differentiate between melanocytes that are synthesizing melanin and those that are not. TYR, TYRP1 and DCT were among the five most differently expressed genes between these two groups. Population genetic analyses of sequence haplotypes of the proximal regulatory flanking-regions included Tajima's D, HEW and DHEW neutrality tests analysis. These were complemented with EHH tests (among others) in which the significance was obtained by a novel approach using extensive simulations under the coalescent model with recombination. We observe strong evidence for positive selection for TYRP1 alleles in Africans and for DCT and TYRP1 in Asians. However, the overall picture reflects a complex pattern of selection, which might include overdominance for DCT in Europeans. CONCLUSION: Diversity patterns clearly evidence adaptive selection in pigmentation genes in Africans and Asians. In Europeans, the evidence is more complex, and both directional and balancing selection may be involved in light skin. As a result, different non-African populations may have acquired light skin by alternative ways, and so light skin, and perhaps dark skin too, may be the result of convergent evolution.

Cutaneous reactive angiomatosis associated with chronic lymphoid leukemia.

Cutaneous reactive angiomatosis is an unusual benign vascular disorder of the skin usually associated to systemic diseases. It is characterized by lobular or diffuse proliferation of small blood vessels with hyperplasia of endothelial cells, pericytes, and sometimes histiocytes. We report a 59-year-old man with asymptomatic erythematous-violaceous patches on back, palms, and elbows for 9 months. Laboratory examination revealed changes consistent with B-chronic lymphocytic leukemia. Cutaneous biopsy showed a predominantly lobular small blood vessel proliferation in dermis with pericytic hyperplasia and mild perivascular lymphoplasmacytic infiltrate. Spontaneous involution of lesions occurred after 6 months. A second biopsy performed at the beginning of clinical involution showed a less prominent vascular component with perivascular giant cells with coexpression of CD68 and CD 31. To our knowledge, this is the first case of cutaneous reactive angiomatosis with documented histopathological findings of clinical involution.

Cutaneous polyarteritis nodosa.

The term polyarteritis nodosa (PAN) presently includes classic systemic PAN, cutaneous PAN, and microscopic PAN (microscopic polyangeiitis). Cutaneous PAN involves the deep dermis and the panniculus, with anatomopathological findings diagnostic for arteritis. The most frequent clinical manifestation of cutaneous PAN is the presence of nodules on the lower legs, which frequently are found at different stages of development. At times, they may not leave residual changes, but generally a violaceous livedoid color or pigmentation with retiform appearance persists for months and even years. Ulceration also is a frequent complication of cutaneous PAN. Pain, arthralgias, malaise, and moderate fever are frequently associated symptoms. Histopathologically, cutaneous PAN shows a single artery involved with diagnostic inflammatory changes. The involved artery is always located in the deep dermis or in the panniculus. Inflammatory active skin nodules show a necrotizing arteritis with variable amounts of fibrinoid necrosis and leukocytoclasia, edema and inflammatory cells. The presence of focal panniculitis surrounding the involved artery is characteristic, in contrast with the more diffuse panniculitis usually found in other nodular diseases. Cutaneous PAN has a variable course, with repeated exacerbations. Salicilates relieve the pain in most instances and may be the only treatment required to improve the symptoms in patients with moderate flare-ups. A short course of corticosteroids therapy at a moderate dose is the most effective treatment to relieve the symptoms and to reduce the inflammation. Patients with an increased ASO titer should always be treated with penicillin.

Clinical and radiological control of highly active relapsing-remitting multiple sclerosis with first-line natalizumab.

A 33-year-old man with gait instability, weakness of the left lower extremity, decreased visual acuity in the left eye, and urgency and urine incontinence was diagnosed of relapsing-remitting multiple sclerosis. He was treated with natalizumab (300 mg intravenously every 4 weeks) as first-line therapy, which reached at 6 months a favorable clinical evolution and dramatic radiological improvement (T2-weighted lesion load decreased by 50% and no gadolinium-enhancing T1 lesions) sustained over the course of 8 years. This clinical case shows the efficacy of natalizumab in a real-world setting and, particularly, the sustained effect of this drug in the long term as demonstrated by persistent radiological improvement. Natalizumab can be considered as the treatment of choice in relapsing-remitting multiple sclerosis forms presenting with two relapses and gadolinium-enhancing (Gd+) lesions.

[Managing the discharge of diabetic patients from the emergency department: a consensus paper]. / Documento de consenso sobre el manejo al alta desde urgencias del paciente diabético.

EN: Eighty to 90% of patients attended in emergency departments are discharged to home. Emergency department physicians are therefore responsible for specifying how these patients are treated afterwards. An estimated 30% to 40% of emergency patients have diabetes mellitus that was often decompensated or poorly controlled prior to the emergency. It is therefore necessary to establish antidiabetic treatment protocols that contribute to adequate metabolic control for these patients in the interest of improving the short-term prognosis after discharge. The protocols should also maintain continuity of outpatient care from other specialists and contribute to improving the long-term prognosis. This consensus paper presents the consensus of experts from 3 medical associations whose members are directly involved with treating patients with diabetes. The aim of the paper is to facilitate the assessment of antidiabetic treatment when the patient is discharged from the emergency department and referred to outpatient care teams.

ES: El 80-90% de los pacientes atendidos en los servicios de urgencias son dados de alta desde los mismos, y por tanto los facultativos de urgencias son los responsables del tratamiento al alta en dichos pacientes. Se estima que la frecuencia de diabetes mellitus en urgencias es de un 30-40% y en muchos casos dicha diabetes está descompensada o con un mal control metabólico previo, por lo que es necesario establecer pautas de tratamiento antidiabético adecuadas de cara al alta que contribuyan a un adecuado control metabólico de dichos pacientes y favorezca un mejor pronóstico a corto plazo tras el alta, así como mantener una continuidad con la atención ambulatoria por parte de otras especialidades y contribuir a una mejoría del pronóstico a largo plazo. El presente documento es por tanto un consenso de expertos de tres sociedades científicas implicadas directamente en la atención del paciente diabético, que pretende facilitar la valoración del tratamiento al alta desde urgencias en cuanto a la diabetes se refiere y su continuidad asistencial ambulatoria.

Unresectable Recurrent Multiple Meningioma: A Case Report with Radiological Response to Somatostatin Analogues.

Medical treatment of meningiomas is reserved for cases in which surgery and radiotherapy have failed. Given that a high percentage of meningiomas express somatostatin receptors, treatment with somatostatin analogues has been proposed. In addition, these medications have been shown to have an antiproliferative and antiangiogenic effect in vitro. To date, very few cases with clinical response and none with radiological response have been described. The case described here is the first to report a radiological response. A 76-year-old Caucasian male was first diagnosed with unresectable meningioma at age 47. The patient experienced multiple recurrences and underwent three surgeries and radiotherapy over the years from the initial diagnosis. Despite treatment, the disease continued its progression. Based on an Octreoscan positive for tumour uptake, therapy with extended-release somatostatin analogues was started. Although no clinical neurological improvement was observed, magnetic resonance imaging scans revealed a discreet but continuous radiological response over time. After >2 years of continuous administration of lanreotide, the patient remains progression free. In highly selected cases, somatostatin analogue treatment for meningioma may be beneficial. Based on our findings, treatment with somatostatin analogues should be maintained longer than previously described before evaluating treatment response.

Allergic contact dermatitis from cyanamide.

Cyanamide (carbimide or calcium carbimide) has been used to treat chronic alcoholism for more than 45 years. The skin reactions provoked by this medication are very rare and are generally associated with systemic reactions after ingestion of the product. However, allergic contact dermatitis has also been detected on persons who prepare cyanamide for administration to patients. We present a case of work-related allergic contact dermatitis from cyanamide that was confirmed by patch testing.