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Key Points Methylation analysis at ZAP-70 CpG+223 in CLL provides superior prognostic information vs IGHV status or CD38 or ZAP-70 expression. A pyrosequencing method for the feasible assessment of CpG+223 methylation in CLL samples is provided.

Paediatric patients with the syndrome of an inappropriate antidiuretic hormone secretion (SIADH), as a manifestation of inflammatory demyelinating disorders of the central nervous system, have been rarely described until now, in only a few cases of neuromyelitis optica spectrum disorders (NMOSDs). We present a case of relapsing SIADH associated with NMOSD, in an anti-aquaporin-4 antibody positive 14-year-old girl, who is, to our best knowledge, the first reported paediatric patient with relapsing SIADH and NMOSD. Additionally, our case further supports the notion that paediatric encephalomyelitis associated with SIADH should suggest the diagnosis of NMOSD.

SummaryObjectiveTo evaluate safety, tolerability, seizure frequency, and regional variations in treatment responses with the AMPA antagonist, perampanel, in a large extension study during up to 3 years of treatment.MethodsPatients ≥12 years old with partial‐onset seizures despite treatment with 1–3 antiepileptic drugs at baseline completed a perampanel phase III trial and entered extension study 307 (NCT00735397). Patients were titrated to 12 mg/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open‐label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight, electrocardiography [ECG], laboratory values) and seizure outcomes were analyzed; key measures were assessed by geographic regions.ResultsAmong 1,216 patients, median exposure was 1.5 years (range 1 week to 3.3 years), with >300 patients treated for >2 years. Treatment retention was 58.5% at cutoff. AEs reported in ≥10% of patients were dizziness, somnolence, headache, fatigue, irritability, and weight increase. Only dizziness and irritability caused discontinuation in >1% of patients (3.9% and 1.3%, respectively). The only serious AEs reported in >1% of patients were epilepsy‐related (convulsion, 3.0%; status epilepticus, 1.1%). No clinically relevant changes in vital signs, ECG or laboratory parameters were seen. After titration/conversion, responder rate and median percentage change from baseline in seizure frequency were stable: 46% for both measures at 9 months (in 980 patients with ≥9 months' exposure) and 58% and 60%, respectively, at 2 years (in the 337 patients with 2 years' exposure). Median percentage reduction in frequency of secondarily generalized (SG) seizures ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the 694 patients with maintenance data ≥1 year, 5.3% were seizure‐free for the entire year.SignificanceNo new safety signals emerged during up to 3 years of perampanel exposure in 39 countries. Seizure responses remained stable, with marked reductions, particularly in SG seizures.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Gallstone diseases are common during pregnancy. In most cases, patients are asymptomatic and do not require any treatment. However, choledocholithiasis, cholangitis, and gallstone pancreatitis may potentially become life‐threatening for both mother and fetus and often require urgent intervention. Although endoscopic retrograde cholangiopancreatography (ERCP) has become the standard technique for removing common bile duct stones, it is associated with ionizing radiation that could carry teratogenic risk. Non‐radiationERCP(NR‐ERCP) is reported to be effective without incurring this risk. Two techniques have been described to confirm bile duct cannulation: bile aspiration and image guidance. With bile aspiration, biliary cannulation is confirmed by applying suction to the cannula to yield bile, thus confirming an intrabiliary position. Image guidance involves using ultrasound or direct visualization (choledochoscopy) to confirm selective biliary cannulation or duct clearance. Once cannulation is achieved, the stones are removed using standardERCPtechniques and tools. Case series and retrospective studies have reported success rates of up to 90% forNR‐ERCPwith complication rates similar to standardERCP. Pregnancy outcomes are not adversely affected byNR‐ERCP, but whether the avoidance of radiation carries benefit for the baby is unknown. Prospective comparative trials are lacking.NR‐ERCPis technically demanding and should be attempted only by skilled biliary endoscopists in properly equipped and staffed health‐care institutions, in a multidisciplinary setting.

AbstractIn 1963, the first bronchoscopic lung biopsy was performed. Less than 10 years later, the technique of transbronchial lung biopsy using a flexible bronchoscope was introduced into clinical practice, significantly reducing the rate of major complications and the rate of surgical lung biopsies in patients with diffuse parenchymal lung diseases. The diagnostic yield of transbronchial lung biopsy varies among various parenchymal lung diseases. In pulmonary sarcoidosis and lymphangitis carcinomatosa, a diagnosis can be obtained in up to 80% of patients. This method is considered inadequate, however, in identifying more complex histological patterns such as usual interstitial pneumonitis or nonspecific interstitial pneumonitis. Introduction of the ‘jumbo forceps’ and of a more ‘surgically oriented’ procedural setting (patients deeply sedated and intubated) allowed larger and more numerous lung specimens to be obtained without a significant increase of complications such as pneumothorax or bronchial bleeding. However, the possibility to obtain enough parenchymal tissue for a morphological diagnosis of complex patterns remained unmet. Recently, the use of cryoprobes has achieved a significant impact on this issue allowing to obtain large quantity of tissue. Recent studies document that with transbronchial cryobiopsies the diagnosis of usual interstitial pneumonitis can be made confidently by pathologists with a good inter‐observer agreement. Pneumothorax is the main complication (reported in up to one fourth of cases in some series); bronchial bleeding is easily controlled using Fogarty balloon. Transbronchial cryobiopsy is a promising new technique that may become a valid alternative to surgical lung biopsy in the near feature.

BACKGROUND:Youth ice hockey is an exciting sport with growing participation in the United States. Updated assessment of injury patterns is needed to determine risk factors for severe injury and develop preventive efforts. The purpose of this study was to evaluate our experience as a level 1 pediatric trauma center in Minnesota treating injured youth ice hockey players.METHODS:Children ≤18 years old who presented to our institution from July 1997 to July 2013 with an injury sustained while participating in ice hockey were identified. Patient demographic information, injury characteristics, and outcomes including use of computed tomography, hospital admission, and procedures were obtained. Age- and gender-specific patterns were determined for injuries and outcomes.RESULTS:Over 16 years, 168 injuries in 155 children occurred, including 26 (15.5%) injuries in girls. Extremity injuries were most common, followed by traumatic brain injury. Injuries to the spine, face, and trunk were less common. Traumatic brain injury and injuries to the spine were most common in younger children (≤14 years old) and girls, whereas injuries to the face were most common in older players (≥15 years old). Most injuries resulted from intentional contact. Admission to the hospital was needed in 65 patients, including 14 (8.3%) who needed intensive care. A major procedure was needed by 23.2% of patients because of their injuries.CONCLUSIONS:Youth ice hockey trauma can be severe, necessitating a thorough evaluation of injured children. Injury patterns are influenced by age and gender, providing an opportunity for targeted preventive efforts.

Percutaneous Lead Revision for Cardiac PerforationIntroductionCardiac perforation is an infrequent but potentially life‐threatening complication associated with placement of a cardiac implantable electronic device (CIED). The objective of this study was to determine the outcomes of percutaneous lead revision in patients who had lead perforation of the myocardium after CIED placement.Methods and ResultsWe reviewed records of 1,458 patients who underwent CIED lead extraction or repositioning. Of these, 31 (2.1%) had the procedure performed for lead perforation as a complication of CIED placement. Demographic, clinical, and follow‐up characteristics of the patients were analyzed. Mean (SD) patient age was 65 (23) years. Cardiac perforation was detected within 24 hours after implantation in 9 patients, within 1 month in 17, and greater than 1 month in 5. Pericardiocentesis was performed with a pigtail drainage catheter in place before the lead revision in 17 patients (55%) who had pericardial effusion, with or without hemodynamic compromise. All culprit leads were successfully managed with percutaneous lead removal (n = 3 [10%]), new lead placement (n = 12 [38%]), or lead repositioning (n = 16 [52%]). Of the 17 patients with pericardiocentesis before the reoperation, none had tamponade develop; in contrast, 3 of the remaining 14 patients had tamponade develop and required urgent pericardiocentesis. All patients survived without requiring open chest surgery.ConclusionPercutaneous removal or repositioning of the perforating lead is feasible and appears effective. Placement of a prophylactic pericardial drain catheter may reduce the incidence of urgent pericardiocentesis during or after a procedure.