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

PurposeSome 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.MethodsRAS 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).ResultsTwenty-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).ConclusionThirteen 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.

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.

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.

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.

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.

Cardiopulmonary and inflammatory biomarkers in the assessment of the severity of canine dirofilariosis.

The prognosis and success of adulticide treatment depends on the baseline severity of infection with Dirofilaria immitis in dogs and can influence the therapeutic protocol to choose. A study was conducted to assess the utility of the cardiopulmonary biomarkers N-terminal of the prohormone brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), myoglobin, and D-dimer, as well as the biomarker of inflammation C-reactive protein (CRP) to evaluate the severity of canine heartworm disease in different stages. Serum samples were collected from 20 heartworm-infected dogs for measurement of these biomarkers. Dogs were assigned to four groups (n=5/group) according to the severity of the disease: Class I and Class II dogs showed concentrations of biomarkers generally within normal ranges for healthy dogs, except CRP in dogs classified as Class II, which showed values slightly above laboratory reference values (19.46±5.69mg/l). Dogs of Class III showed elevated levels of NT-proBNP (1220.12±465.18pmol/l) (p<0.05), cTnI (0.99±0.39ng/ml), CRP (33.98±7.99mg/l) (p<0.05), and 40% of these dogs (2/5) presented pathological values of D-dimer and myoglobin (p<0.05). Dogs of Class IV (caval syndrome) presented elevated levels of NT-proBNP (>2530.8pmol/l), cTnI (1.99±0.32ng/ml), and CRP (80.24±47.69mg/l); all Class IV dogs showed pathological elevations of D-dimer (0.81±0.46ng/ml), and 60% (3/5) of these dogs showed pathological elevations of myoglobin (significant elevations [p<0.05] for all biomarkers with respect to reference values and values for dogs in Classes I, II, and III). In canine heartworm disease, chronic presence of D. immitis causes a proliferative endoarteritis, thromboembolisms, pulmonary hypertension, and right-sided congestive heart failure. As the severity of the disease worsens, serum values of cTnI, myoglobin, and NT-proBNP increase, indicating significant cardiac damage. The finding of pathological concentrations of D-dimer suggests the presence of thromboembolism and/or disseminated intravascular coagulation. CRP increases according to the severity of the disease, indicating inflammatory processes that could contribute to the progression of the disease. These preliminary results demonstrate the utility of cardiopulmonary and inflammation biomarkers to assist in the establishment of the severity of canine heartworm disease.

Acute phase response in dogs with Dirofilaria immitis.

The aim of this study was to determine concentrations of different positive and negative acute phase proteins (C-reactive protein, haptoglobin, albumin and paraoxonase-1) in dogs naturally infected with Dirofilaria immitis at the time of diagnosis. 194 dogs were included in the study. All were evaluated for the presence or absence of D. immitis circulating antigens and for the presence or absence of microfilariae and a clinical examination was carried out. 38 dogs were negative and 156 dogs were positive for circulating D. immitis antigens. A significant increase in C-reactive protein and significant decreases in albumin and paraoxonase-1 activity were observed in positive dogs. These changes appeared with independence of the presence/absence of microfilariae or clinical signs. C-reactive protein was the only acute phase protein that showed significant differences between asymptomatic and symptomatic dogs. Interestingly, the increases seen in C-reactive protein values were not accompanied by increases in haptoglobin, and haptoglobin even decreased in the dogs with microfilaria. This could be due to the hemolytic anemia which can be produced in dirofilariasis. In conclusion, there is an acute phase response (with increases in C-reactive protein and decreases in albumin and paraoxonase-1) and a divergence in the behaviour between C-reactive protein and haptoglobin in dogs with D. immitis.

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.

Spanish Registry for Embolization of Small Intracranial Aneurysms with Cerecyte Coils (SPAREC) Study. Early Experience and Mid-Term Follow-up Results.

SUMMARY: This study aimed to report the results obtained in treating small ruptured and unruptured intracranial aneurysms using Cerecyte coils. A prospective, non-randomized multicenter registry operating in Spain with a reporting period between May 2005 and September 2007.We present clinical and angiographic results for 48 small aneurysms (26 ruptured, five with III cranial nerve paresis, and 17 incidental) that had undergone six months' follow-up. The volumetric percentage occlusion (VPO) achieved and percentage bioactive coils (PBC) used were assessed. No episodes of bleeding occurred during the follow-up period. The technical complication rate was 10.4% (five cases): four thromboembolic complications resolved with medication (8.3%) and one asymptomatic protrusion of a coil into the parent vessel. The clinical complication rate for the procedure was 2.1% (occlusion of the anterior choroidal artery in a ruptured anterior choroidal anaeurysm). Mean VPO was 25.2%. Balloon-assisted technique (BAT) was used in 60.4% of cases. The VPO was higher in the BAT-treated cases (P < 0.05). The overall six-month recanalization rate was 16.7% (12.5% minor and 4.2% major recanalizations). Neck size and VPO were unrelated to the recanalization rate. The PBC was higher in cases with progressive Deployment of the device is safe from the standpoint of periprocedural technical and clinical complications. No episodes of hemorrhage were recorded during follow-up. The sixmonth recanalization and retreatment rates compared favorably with most endovascular platinum and bioactive coil series.

[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.

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.