A collaborative system for endovascular treatment of acute ischaemic stroke: the Madrid Stroke Network experience.

BACKGROUND AND PURPOSE: The complexity and expense of endovascular treatment (EVT) for acute ischaemic stroke (AIS) can present difficulties in bringing this approach closer to the patients. A collaborative node was implemented involving three stroke centres (SCs) within the Madrid Stroke Network to provide round-the-clock access to EVT for AIS. METHODS: A weekly schedule was established to ensure that at least one SC was 'on-call' to provide EVT for all those with moderate to severe AIS due to large vessel occlusion, >4.5 h from symptom onset, or within this time-window but with contraindication to, or failure of, systemic thrombolysis. The time-window for treatment was 8 h for anterior circulation stroke and <24 h in posterior stroke. Outcomes measured were re-canalization rates, modified Rankin Scale (mRS) score at 3 months, mortality and symptomatic intra-cranial haemorrhage (SICH). RESULTS: Over a 2-year period (2012-2013), 303 candidate patients with AIS were considered for EVT as per protocol, and 196 (65%) received treatment. Reasons for non-treatment were significant improvement (14%), spontaneous re-canalization (26%), clinical worsening (9%) or radiological criteria of established infarction (31%). Re-canalization rate amongst treated patients was 80%. Median delay from symptom onset to re-canalization was 323 min (p25; p75 percentiles 255; 430). Mortality was 11%; independence (mRS 0-2) was 58%; SICH was 3%. CONCLUSIONS: Implementation of a collaborative network to provide EVT for AIS is feasible and effective. Results are good in terms of re-canalization rates and clinical outcomes.

Skin manifestations of chronic kidney disease.

Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions.

First-Pass Effect in M1-Occlusion Stroke Patients Treated with Combined Stent-Retriever/Large-Bore Distal Aspiration Catheter Thrombectomy.

INTRODUCTION: Combined stent-retriever/large-bore distal aspiration catheter (LB-DAC) thrombectomy was recently introduced to treat large-vessel occlusion; however, it is unclear whether larger inner diameters improve outcomes. We compared angiographic and clinical outcomes in patients with occlusions of the M1 segment of the middle cerebral artery treated with mechanical thrombectomy using extra-LB-DAC versus LB-DAC in combination with stent-retrievers. METHODS: We analyzed consecutive patients with M1 occlusion included in the ROSSETTI registry treated with non-balloon guide catheter combined LB-DAC/stent-retriever thrombectomy between June 2019 and April 2022. We compared demographics, baseline clinical variables, procedural variables, angiographic outcomes, and clinical outcomes [National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) and modified Rankin scale score at 3 months] between patients treated with extra-LB-DAC (Sofia Plus, MIVI Q6, Catalyst7; inner diameter, 0.068″-0.070″) versus LB-DAC (Sofia 5F, MIVI Q5, Catalyst 6; inner diameter, 0.055″-0.064″). Primary outcome was the first-pass effect (FPE) rate, defined as near-complete/complete reperfusion (mTICI 2c-3) after a single pass of the device. RESULTS: We included 324 patients (extra-LB-DAC, 185, 57.1% patients). Demographics, clinical data, and clinical outcomes were similar between the two groups; however, there was a trend towards improvement in National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) in the cohort treated with extra-LB-DAC 9 points (IQR 4;16 points) vs. 12 points (IQR 4;18 points, P = 0.083). Patients treated with extra-LB-DAC had higher FPE rate (47% vs. 30.9%; P = 0.003) and higher modified FPE (mTICI ≥ 2b after a single pass) rate (65.9% vs 46.8%; P = 0.001). The use of extra-LB-DAC was an independent factor in predicting FPE (odds ratio 1.982, 95% confidence interval 1.250-3.143, P = 0.004). CONCLUSION: Our results suggest that in combined LB-DAC/stent-retriever thrombectomy, a larger aspiration catheter inner diameter is associated with higher rates of FPE and mFPE.

Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer.

PURPOSE: Some patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications. METHODS: RAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies). RESULTS: Twenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test). CONCLUSION: Thirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer.

BACKGROUND: Combination of bevacizumab and FOLFIRI has currently become one of the standard therapeutic regimens. However, published information is still limited. The objective of the present retrospective observational study is to analyse the response and toxicity of first-line treatment with FOLFIRI+bevacizumab in patients with metastatic colorectal cancer (mCRC). METHODS: Data were collected from patients from nine Spanish sites diagnosed with mCRC, ECOG≤2, whose first treatment for advanced disease was at least three cycles of FOLFIRI+bevacizumab. RESULTS: A total of 95 patients were enrolled into the study: 64.2% males, median age of 59 years (53.2-67.1 years), ECOG=0-1 in 96.9% of patients. The main site of primary tumour was the colon (69.7%), and most metastases occurred in the liver (71.6%). Clinical benefit was detected in 67.4% (57.0-76.6; 95% confidence interval (CI)), with 8.4% of CR and 42.1% of PR. Median TTP was 10.6 months (10.0-11.3; 95% CI), PFS was 10.6 months (9.8-11.3; 95% CI), and OS was 20.7 months (17.1-24.2; 95% CI). Main grade I-II toxicities included haematological toxicity (35.8%), diarrhea (27.3%), mucositis (25.3%), asthenia (19.0%), haemorrhages (11.6%), and emesis (10.6%). Toxicities reaching grades III-IV were haematological toxicity (9.5%), diarrhea (8.5%), mucositis (5.3%), hepatic toxicity (2.1%), asthenia (2.1%), proteinuria (1.1%), emesis (1.1%), pain (1.1%), and colics (1.1%). CONCLUSION: Results of this study support the beneficial effect of adding bevacizumab to FOLFIRI regimen in terms of efficacy and show a favourable tolerability profile.

First-line panitumumab plus docetaxel and cisplatin in advanced gastric and gastro-oesophageal junction adenocarcinoma: results of a phase II trial.

PURPOSE: Panitumumab is extensively used for RAS-WT metastatic colorectal cancer. This study assessed the efficacy and safety of panitumumab plus first-line chemotherapy [docetaxel (DOC) and cisplatin (CIS)] in treatment-naïve advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma (ADC) patients. METHODS: Phase II, open-label, single-arm study includes treatment-naïve advanced gastric or GEJ-ADC patients from ten Spanish centres. Patients received panitumumab (6 mg/kg) plus DOC and CIS (50 mg/m2 both) every 2 weeks until disease progression, unacceptable toxicity, or patient withdrawal. Primary endpoint: objective response rate (ORR); main secondary endpoints: disease control rate (DCR), duration of response (DoR), time to progressive disease (TTP), progression-free-survival (PFS), overall survival (OS), and safety. RESULTS: Forty-four patients were included; median age: 67.8 (range 43.3-82.7) years, 68.2% male. The ORR was 27.3% (95% CI 15.0, 42.8); median PFS and OS: 5.0 (95% CI 3.6, 6.9) and 7.2 (5.5, 9.0) months, respectively. Median TTP, DCR and DoR: 5.3 (range 3.8-7.0) months, 70.5% (95% CI 54.8, 83.2%), and 4.8 (1.8, NE) months. Median panitumumab treatment duration: 11.9 (range 0.1-34.9) weeks; 25.0% patients had a dose reduction and 40.9% discontinued treatment. Grade 3-4 adverse events (AEs): 68.2%/22.2% patients. Most common AEs: asthenia (75.0%) and mucosal inflammation (54.5%). Serious AEs were experienced by 54.6% patients; 9.1%, 13.6%, and 15.9% related to panitumumab, DOC, and CIS, respectively. Three (6.8%) patients died due to AEs not related to study treatment. CONCLUSIONS: The addition of panitumumab to standard chemotherapy as the first-line treatment in advanced gastric or GEJ-ADC does not appear to improve the efficacy outcomes.

Efficacy and safety of trifluridine/tipiracil in third-line and beyond for the treatment of patients with metastatic colorectal cancer in routine clinical practice: patterns of use and prognostic nomogram.

INTRODUCTION: Trifluridine/tipiracil combination has shown a benefit over placebo in the treatment of patients with chemorefractory metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of this combination in the real-life setting at eight Galician centers in Spain. PATIENTS AND METHODS: This is a retrospective study of a cohort of patients with mCRC in treatment with trifluridine/tipiracil within usual clinical practice who have been previously treated or are not considered candidates for treatment with available therapies. RESULTS: A total of 160 mCRC patients were included. Our data showed that 11.9% of patients achieved disease control. Median progression-free survival was 2.75 months; at 5.66 months follow-up, median overall survival was 7.94 months. Asthenia and neutropenia (48.1% both) were the most frequent adverse events. Overall survival was lower in patients with ECOG 2, multiple metastatic sites, platelets count 350,000/µl, alkaline phosphatase > 500 IU/l, and carcinoembryonic antigen > 10 ng/ml. CONCLUSION: The results of this study confirm the efficacy and safety of trifluridine/tipiracil in chemorefractory mCRC patients. However, patients in clinical practice differ from patients in clinical trials. Due to this, prognostic factors have special importance to offer the best therapeutic approach.

Correction to: Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine and Oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial.

Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine.

Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine and Oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial.

PURPOSE: The phase III ToGA trial established cisplatin, fluoropyrimidine and trastuzumab as the standard treatment in HER2-positive advanced gastric cancer (AGC). However, as demonstrated in HER2-negative AGC, oxaliplatin-based regimens could improve tolerance remaining effective. The aim of this trial was to explore the potential activity and safety of capecitabine, oxaliplatin (XELOX) and trastuzumab in patients with HER-2 positive advanced gastric cancer. METHODS: We conducted a multicentre, prospective, non-randomised, non-controlled, open-label and national (Spanish) phase II study. Patients with HER2-positive advanced gastric or gastro-oesophageal junction (EGJ) cancer received XELOX and trastuzumab as first-line treatment. Primary endpoint was objective tumour response rate (ORR). RESULTS: 45 patients from ten hospitals in Spain were included from September 2011 to December 2013. Median age was 65 years, 82.2% were male, 69% had gastric cancer and 31% had EGJ tumours. At a median follow-up of 13.7 months (7.1-20.9), the estimated median progression-free survival and overall survival were 7.1 (95% CI 5.5-8.7) and 13.8 months (95% CI 10.1-17.4), respectively, with 8.9%, 37.8% and 31.1% of patients achieving complete response, partial response and stable disease. Regarding safety, 44.4% of the patients had grade 3 or greater adverse events, being the most frequent diarrhoea (26.6%), fatigue (15.5%), nausea (20%) and vomiting (13.3%). Only two patients (4.4%) developed asymptomatic grade 2 left ventricle ejection fraction reduction. CONCLUSIONS: XELOX-trastuzumab is a promising and effective therapy as first-line treatment for patients with HER2-positive AGC, with comparable results to the ones obtained with other "platinum-based" regimens. This scheme is feasible and tolerable with a low incidence of cardiac toxicity.

Endovascular treatment of intracranial aneurysms using the Pipeline Flex embolization device: a case series of 30 consecutive patients.

BACKGROUND: The Pipeline Flex embolization device has some peculiarities in comparison with the previous generation device. Despite recent reports of the modified delivery system, its safety is still unknown. OBJECTIVE: To illustrate the intraprocedural and periprocedural complication rate with this new device in 30 consecutive patients. MATERIAL AND METHODS: Clinical, procedural, and angiographic data, including aneurysm size and location, device or devices used, angiographic and clinical data were analyzed. RESULTS: 30 patients harboring 30 aneurysms were analyzed. 39 devices were placed properly. Multiple Pipeline embolization devices (PEDs) were used in 7 cases. In 28 devices the distal end opened fully from the beginning with a complete wall apposition. In the remaining 11 devices, distal-end opening of the devices was instant but partial, but fully opened easily after recapture. Among the 30 procedures, recapture and reposition of the Pipeline Flex was performed four times owing to proximal migration/malposition of the device during delivery. Four intraprocedural/periprocedural complications occurred, of which 2 resulted in major complications, with neurologic deficits persisting for longer than 7 days. The 30-day morbidity rate was 6.6%, with no deaths. No aneurysm rupture or parenchymal hemorrhage was seen. CONCLUSIONS: The Pipeline Flex embolization device allows more precise and controlled deployment than the first-generation device. The number of devices and the complication rate during the learning curve are lower than reported with the first-generation PED. The new delivery system and the resheathing maneuvers do not seem to increase the intraprocedural complication rate in comparison with the first-generation PED.

[Neonatal hearing loss screening: our results three years after starting the program]. / Despistaje de la hipoacusia neonatal: resultados después de 3 años de iniciar nuestro programa.

Since the 90s there increasing interest in early detection of neonatal hearing loss due to the feasibility of universal neonatal screening as well as to the possibility of early intervention. This has led to set up neonatal screening programs based upon otoacoustic emissions and to a great increase in the number of publications in the field. Our hospital started a neonatal hearing loss screening program using otoacoustic emission in March 2000. We used a Capella Cochlear Emissions (MADSEN electronics) equipment. Until May 2003 we have performed the test in 6372 children with a median age of 71 days. In our study, the sensibility of the test was 90.9% and the specificity 99.7%. Our results are similar to those reported in the literature although the age of the children was higher and we have found an incidence of hearing loss lower than other studies.

Acute phase protein response in heartworm-infected dogs after adulticide treatment.

During the adulticide treatment of Dirofilaria immitis the worms die releasing fragments of parasites and causing pulmonary thromboembolisms which could exacerbate the clinical condition. To determine the utility of acute phase proteins (APPs) to monitor the progression of the treatment, different positive [C-reactive protein (CRP), haptoglobin (hp)] and negative [albumin, paraoxonase-1(PON-1)] APPs were measured in 15 heartworm-infected dogs (5 with high and 10 with low parasite burden) following adulticide treatment. The results showed increased concentrations of CRP, decreased concentrations of haptoglobin and PON-1 in infected dogs before starting the treatment. Progressive but not significant increases were observed in PON-1 activity and albumin concentration along the treatment. After the treatment with doxycycline and ivermectine a decrease in CRP and Hp levels was experienced, which could reflect a reduction of the vascular inflammation caused by the elimination of Wolbachia and reduction of microfilariae. Fifteen days after the first melarsomine injection, marked increases in CRP and Hp were observed, which could be due to pulmonary inflammation and thromboembolism caused by the post-adulticide death of the worms. This increase was greater in dogs with high parasite burden. As the pathology disappeared, there was an improvement in the concentrations of CRP and Hp, returning into reference values in dogs with low parasite burden at the end of the treatment. The measurement of CRP and Hp could be a resource of support to evaluate the magnitude of the post-adulticide complications during the adulticide treatment of D. immitis.

Relationship of HHV8 replication and Kaposi's sarcoma after solid organ transplantation.

HHV8 DNA sequences have recently been isolated from all types of Kaposi's sarcomas, and its association in the etiopathogenesis of this tumor has been established. However, little is known about the regulation of HHV8 replication in immunocompromised patients seropositive for this virus, and its impact on the development of Kaposi's sarcoma (KS). Through the study of a heart transplant patient who developed KS and in whom peripheral blood lymphocytes (PBLs) had been prospectively collected before and after transplantation, we have investigated the pathogenesis of HHV8. Our results indicate that (i) HHV8 can reactivate soon after transplantation; (ii) viral replication, as determined by quantification of HHV8 DNA load of PBLs, increases significantly after transplantation; and (iii) increased HHV8 DNA levels in PBLs are associated with the development of KS.

Novel mutation in the CMV UL97 gene associated with resistance to ganciclovir therapy.

Cytomegalovirus (CMV) strains resistant to ganciclovir have been associated with specific mutations in the UL97 and UL54 genes. The UL97 gene of a CMV strain isolated from a renal transplant recipient before and after 438 days of ganciclovir treatment was amplified by polymerase chain reaction and sequenced. A novel mutation resulting in deletion of codons 595 to 603 was identified in the viral DNA from specimens obtained after, but not before, prolonged ganciclovir therapy. Clinical and virological resolution of CMV disease occurred after switching to foscarnet therapy. Although many ganciclovir resistance mutations have been mapped to the UL97 codon range 591-607, this one is unusual in that it involves deletion of half these codons. Because UL97 seems to be necessary for effective CMV replication, this deletion suggests that much of codons 591-607 can be removed without destroying the biological function of UL97, and that this codon range can be altered in various ways to affect ganciclovir susceptibility. Rapid, flexible genotypic assays directed at this part of UL97 may facilitate the early recognition of ganciclovir resistance.

Human herpesvirus 6 seronegativity before transplantation predicts the occurrence of fungal infection in liver transplant recipients.

BACKGROUND: Invasive fungal infection has a major impact on the morbidity and mortality of liver transplant recipients. Human herpesvirus (HHV)-6 infection after transplantation is associated with an immunosuppressive state and the development of cytomegalovirus disease. Because cytomegalovirus infection is a risk factor for invasive fungal infection after transplantation, we have examined whether HHV-6 and fungal infection are associated after transplantation. METHODS: Pretransplantation sera from 247 consecutive liver transplant recipients were analyzed for IgG to HHV-6. Thirty-three (13%) HHV-6-seronegative recipients were identified. Six of 33 (18%) seronegative recipients experienced fungal infection as compared with 15 of 214 (7%) seropositive recipients (P=0.034). RESULTS: In a univariate analysis of risk factors for fungal infection, pretransplantation seronegativity to HHV-6 (P=0.034), intraoperative cryoprecipitate requirements greater than the 75th percentile (P=0.035), reoperation (P=0.005), biliary stricturing postoperatively (P=0.046), and gastrointestinal or vascular complications postoperatively (P=0.030) were identified as significant risk factors. Moreover, in pairwise multivariate analysis, pretransplantation HHV-6 seronegativity remained a significant variable even in the presence of each of the other variables. CONCLUSIONS: These results suggest that HHV-6 seronegativity before transplantation is a valuable clinical marker that identifies patients at risk for developing fungal infection after transplantation.

Five-year follow-up of hepatitis C-naïve heart transplant recipients who received hepatitis C-positive donor hearts.

BACKGROUND: Due to the risk of transmission of hepatitis C virus, the use of hepatitis C seropositive donors in heart transplantation is controversial. The transmission rate of hepatitis C in this patient population is estimated to range from 67% to 80%. Long-term clinical outcomes of heart transplant recipients of hepatitis C-positive donor hearts are not well described. We report the 5-year long-term outcome of seven hepatitis C-naïve heart transplant recipients who received hepatitis C-positive donor hearts. METHODS: Retrospective analysis of clinical course, liver biochemistry, serology, and hepatitis C virology data. RESULTS: Seven hearts transplant recipients, six men and one woman were included in our study. After a mean follow-up of 63.3 +/- 20.4 months (range 28.2 to 85.9), four of seven (57.1%) patients are hepatitis C-negative, have normal liver function tests, and no clinical evidence of hepatitis. Three of seven (43%) have been diagnosed with hepatitis C by liver biopsy or the HCV-RNA reverse transcriptase polymerase chain reaction at a mean follow-up of 35.1 months (18.8 months posttransplantation). One had an accelerated course of hepatitis that was ultimately fatal, one was successfully treated with interferon, and the third died from other causes than liver injury. Overall, the 5-year survival was 71.4%. CONCLUSIONS: The 5-year survival of hepatitis C-naïve recipients of hearts from hepatitis C-positive donors is similar to heart transplant recipients with hepatitis-negative donor hearts. Nevertheless, the transmission rate is high and hepatitis C infection in this population can lead to considerable morbidity and accelerated, fatal hepatitis.

Nerve growth factor receptor immunoreactivity in non-nervous structures of the adult rat brain.

The non-neuronal distribution of nerve growth factor receptors (NGFr) in the adult rat brain was investigated immunohistochemically using an anti-NGFr monoclonal antibody (192-IgG). In addition to the neurons known to be NGF-dependent or containing NGF binding-sites, a moderate to strong NGFr immunoreactivity was observed in several non-nervous tissues such as the ependymal cells, the epithelial cells of the choroid plexus, the leptomeninge and the cerebral blood vessels. Vascular immunoreactivity for NGFr occurs in the adventitia and muscular layers of the large arteries (circle of Willis) and, apparently, in all the wall layers of the intermediate or small (pial-arachnoid) arteries. The present results provide direct evidence for the presence of non-neuronal NGFr in the brain of adult rats, and suggest a possible involvement of NGF in roles other than those classically thought.

Diagnostic value of a miracidium in urinary sediment.

Although rarely encountered in the United States, urinary tract schistosomiasis occurs commonly in many countries in the eastern hemisphere. Travel and immigration may contribute to imported cases of schistosomiasis. Excessive morbidity and increased mortality, including the development of urinary-tract squamous-cell carcinoma, are associated with untreated Schistosoma haematobium infection. Therefore, in the appropriate clinical context, all efforts should be made to rule out infectious and readily treatable causes of chronic hematuria. The presence of characteristic eggs in the urinary sediment is the usual means of diagnosing a S. haematobium infection. Additionally, the small and less commonly encountered miracidium stage of S. haematobium may also be present in the urine, which is another means of diagnosing urinary tract schistosomiasis. The present report describes a case in which a miracidium was detected in a fresh, unstained urine specimen. As detection of miracidia can be made in specimens also processed by routine cytologic methods, it behooves cytologists to be aware of this entity for the diagnosis of schistosomiasis.

[Thyroid cancer treatment]. / Le traitement des cancers du corps thyroïde.

INTRODUCTION: Thyroid diseases are common although cancer is rare. There are some controversial issues concerning the extent of surgical treatment of thyroid cancer. MATERIALS AND METHODS: We have studied 614 cases of thyroidectomy inducing 82 of mostly papillary and follicular thyroid cancers. RESULTS AND DISCUSSION: We observed that differentiated thyroid cancer has a predilection for the right lobe and one third of papillary tumors are multifocal. We have seen that fine needle aspiration cytology is the most useful preoperative study. Intraoperative frozen biopsy has a good specificity but sensitivity is low in our series, specially for follicular neoplasms. The treatment in our series consisted in total thyroidectomy and, in differentiated cancers, postoperative I-131. Survival is very good for differentiated cancers. Prognosis is poor for anaplastic carcinoma in the short term.