Abstract Objectives The study objective was to determine the predictors of new-onset arrhythmia among infants with single-ventricle anomalies during the post-Norwood hospitalization and the ...association of those arrhythmias with postoperative outcomes (ventilator time and length of stay) and interstage mortality. Methods After excluding patients with preoperative arrhythmias, we used data from the Pediatric Heart Network Single Ventricle Reconstruction Trial to identify risk factors for tachyarrhythmias (atrial fibrillation, atrial flutter, supraventricular tachycardia, junctional ectopic tachycardia, and ventricular tachycardia) and atrioventricular block (second or third degree) among 544 eligible patients. We then determined the association of arrhythmia with outcomes during the post-Norwood hospitalization and interstage period, adjusting for identified risk factors and previously published factors. Results Tachyarrhythmias were noted in 20% of subjects, and atrioventricular block was noted in 4% of subjects. Potentially significant risk factors for tachyarrhythmia included the presence of modified Blalock–Taussig shunt ( P = .08) and age at Norwood ( P = .07, with risk decreasing each day at age 8-20 days); the only significant risk factor for atrioventricular block was undergoing a concomitant procedure at the time of the Norwood ( P = .001), with the greatest risk being in those undergoing a tricuspid valve procedure. Both tachyarrhythmias and atrioventricular block were associated with longer ventilation time and length of stay ( P < .001 for all analyses). Tachyarrhythmias were not associated with interstage mortality; atrioventricular block was associated with mortality among those without a pacemaker in the unadjusted analysis (hazard ratio, 2.3; P = .02), but not after adding covariates. Conclusions Tachyarrhythmias are common after the Norwood procedure, but atrioventricular block may portend a greater risk for interstage mortality.
Objective The objective of the study was to assess cerclage to prevent recurrent preterm birth in women with short cervix. Study Design Women with prior spontaneous preterm birth less than 34 weeks ...were screened for short cervix and randomly assigned to cerclage if cervical length was less than 25 mm. Results Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered less than 35 weeks ( P = .09). In planned analyses, birth less than 24 weeks ( P = .03) and perinatal mortality ( P = .046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth less than 35 weeks ( P = .006) was reduced in the less than 15 mm stratum with a null effect in the 15-24 mm stratum. Conclusion In women with a prior spontaneous preterm birth less than 34 weeks and cervical length less than 25 mm, cerclage reduced previable birth and perinatal mortality but did not prevent birth less than 35 weeks, unless cervical length was less than 15 mm.
Objective The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin ...transfusion syndrome (TTTS). Study Design This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients. Results There was no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11 of 20) vs 55% (11 of 20) ( P = 1.0, odds ratio OR 1, 95% confidence interval CI 0.242 to 4.14) or recipients at 30% (6 of 20) vs 45% (9 of 20) ( P = .51, OR 1.88, 95% CI 0.44 to 8.64). There was no difference in 30 day survival of 1 or both twins on a per-pregnancy basis between AR at 75% (15 of 20) and SFLP at 65% (13 of 20) ( P = .73, OR 1.62, 95% CI 0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) was not statistically significant for AR at 60% (24 of 40) vs SFLP 45% (18 of 40) ( P = .18, OR 2.01, 95% CI 0.76 to 5.44). There was a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14 of 20) vs the AR arm at 35% (7 of 20) ( P = .25, OR 5.31, 95% CI 1.19 to 27.6). This was offset by increased recipient neonatal mortality of 30% (6 of 20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality ( P = .055, OR 3.025/point) by logistic regression analysis. Conclusion The outcome of the trial did not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS.
Abstract Background We identified a group of patients with ATP1A3 mutations at residue 756 who display a new phenotype, distinct from alternating hemiplegia of childhood, rapid-onset ...dystonia-parkinsonism, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss syndromes. Methods Four patients with c.2267G>A (R756H) mutations from two families and two patients with c.2267G>T (R756L) mutations from one family are described and compared with the previously reported patients with mutations resulting in R756H and R756C protein variants. Results Patients with ATP1A3 R756H have onset in childhood of infrequent, fever-triggered paroxysms of encephalopathy and weakness with slowly improving but persistent deficits. Motor findings of weakness are mostly generalized, and patients may also have bulbar or oculomotor problems. Longer-term outcomes range from mild motor apraxia with near-normal function to persistent dysphagia, dysarthria, cognitive deficit, motor apraxia, and inability to walk because of ataxia. Patients with ATP1A3 R756L have a similar phenotype that includes paroxysmal, stepwise progression of ataxia associated with infections. Conclusions ATP1A3 mutations affecting residue 756 result in a clinical syndrome, separate from those associated with previously described ATP1A3 mutations, which consists chiefly of fever-induced paroxysmal weakness and encephalopathy (FIPWE). Patients with R756L and R756C protein variants display more prominent ataxia, overlapping with the relapsing encephalopathy with cerebellar ataxia syndrome previously described in a patient with the c.2266C>T (R756C) mutation. All patients reported with mutations at residue 756 to date have had a similar episodic course and clinical features. Patients with mutations of ATP1A3 residue 756 appear to have a distinct clinical phenotype compared with patients with other ATP1A3 mutations, with fever-induced encephalopathy as key differentiating feature.
Antinuclear antibody-negative systemic sclerosis Salazar, Gloria A., MD; Assassi, Shervin, MD, MS; Wigley, Fredrick, MD ...
Seminars in arthritis and rheumatism,
06/2015, Letnik:
44, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract Objective To examine the demographic and clinical characteristics of systemic sclerosis (SSc) patients without antinuclear antibodies (ANA) compared to ANA-positive patients. Methods SSc ...patients enrolled in the Scleroderma Family Registry and DNA Repository were included. Relevant demographic and clinical data were entered by participating sites or obtained by chart review. ANA and SSc-related antibodies were determined in all investigated patients using commercially available kits at our laboratories. Results This study included 3249 patients, of whom 208 (6.4%) were ANA negative. The proportion of male patients was higher in the ANA-negative group (OR = 1.65; p = 0.008). ANA-negative patients experienced less vasculopathic manifestations of SSc. The percent predicted diffusing capacity of carbon monoxide (DLCO) was higher in ANA-negative patients ( p = 0.03). Pulmonary arterial hypertension (PAH) per right heart catheterization was less common in the ANA-negative group (OR = 0.28; p = 0.03). Furthermore, patients with negative ANA had a lower prevalence of telangiectasias and digital ulcers/pits (OR = 0.59, p = 0.03 and OR = 0.38, p = 0.01, respectively). Although diffuse cutaneous involvement was more common, the modified Rodnan Skin Score (mRSS) was lower in the ANA-negative group (2.4 points lower, p = 0.05). Furthermore, they experienced more malabsorption ( p = 0.05). There was no difference in the frequency of pulmonary fibrosis or scleroderma renal crisis. All-cause mortality was not different between the 2 groups ( p = 0.28). Conclusions In conclusion, the results of this study suggest that SSc patients who are ANA negative constitute a distinct subset of SSc with less vasculopathy (less PAH, digital ulcers, and fewer telangiectasias), a greater proportion of males, and possibly, more frequent lower gastrointestinal involvement.
Myelofibrosis is a chronic myeloproliferative neoplasm characterised by splenomegaly, cytopenias, bone marrow fibrosis, and debilitating symptoms including fatigue, weight loss, and bone pain. ...Mutations in Janus kinase-2 (JAK2) occur in approximately 50% of patients. The only approved JAK2 inhibitor for myelofibrosis is the dual JAK1 and JAK2 inhibitor, ruxolitinib. 58-71% of patients treated with ruxolitinib in clinical trials so far have not achieved the primary endpoint of 35% or more reduction in spleen volume from baseline assessed by MRI or CT. Furthermore, more than 50% of patients discontinue ruxolitinib treatment after 3-5 years. On the basis of this unmet need, we investigated the efficacy and safety of fedratinib, a JAK2-selective inhibitor, in patients with ruxolitinib-resistant or ruxolitinib-intolerant myelofibrosis.
This single-arm, open-label, non-randomised, phase 2, multicentre study, done at 31 sites in nine countries, enrolled adult patients with a current diagnosis of intermediate or high-risk primary myelofibrosis, post-polycythaemia vera myelofibrosis, or post-essential thrombocythaemia myelofibrosis, found to be ruxolitinib resistant or intolerant after at least 14 days of treatment. Other main inclusion criteria were palpable splenomegaly (≥5 cm below the left costal margin), Eastern Cooperative Oncology Group performance status of 2 or less, and life expectancy of 6 months or less. Patients received oral fedratinib at a starting dose of 400 mg once per day, for six consecutive 28-day cycles. The primary endpoint was spleen response (defined as the proportion of patients with a ≥35% reduction in spleen volume as determined by blinded CT and MRI at a central imaging laboratory). We did the primary analysis in the per-protocol population only (patients treated with fedratinib, for whom a baseline and at least one post-baseline spleen volume measurement was available) and the safety analysis in all patients receiving at least one dose of fedratinib. This trial was registered with ClinicalTrials.gov, number NCT01523171.
Between May 8, 2012, and Aug 29, 2013, 97 patients were enrolled and received at least one dose of fedratinib. Of 83 assessable patients, 46 (55%, 95% CI 44-66) achieved a spleen response. Common grade 3-4 adverse events included anaemia (37 38% of 97 patients) and thrombocytopenia (21 22% of 97), with 18 (19%) patients discontinuing due to adverse events. Seven (7%) patients died during the study, but none of the deaths was drug related. Suspected cases of Wernicke's encephalopathy in other fedratinib trials led to study termination.
This phase 2 study met its primary endpoint, suggesting that patients with ruxolitinib-resistant or ruxolitinib-intolerant myelofibrosis might achieve significant clinical benefit with fedratinib, albeit at the cost of some potential toxicity, which requires further evaluation. Fedratinib development in this setting is currently being assessed.
Sanofi.
Objective This report presents the 30-day results of the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial and evaluates the safety ...and efficacy of ENROUTE Transcarotid NPS (Silk Road Medical Inc, Sunnyvale, Calif), a novel transcarotid neuroprotection system that provides direct surgical common carotid access and cerebral embolic protection via high-rate flow reversal during carotid artery stenting (CAS). Methods A prospective, single-arm, multicenter clinical trial was performed to evaluate the use of the ENROUTE Transcarotid NPS during CAS procedures performed in patients considered to be at high risk for complications from carotid endarterectomy. Symptomatic patients with ≥50% stenosis and asymptomatic patients with ≥70% stenosis were eligible to be treated with any U.S. Food and Drug Administration-approved carotid artery stent. The primary end point was the composite of all stroke, myocardial infarction (MI), and death at 30 days postprocedure as defined in the Food and Drug Administration-approved study protocol. Secondary end points included cranial nerve injury; 30-day stroke, death, stroke/death, and MI; acute device, technical, and procedural success; and access site complications. All major adverse events were adjudicated by an independent clinical events committee. Results Between November 2012 and July 2014, 208 patients were enrolled at 18 sites. Sixty-seven patients were enrolled as lead-in cases, and 141 were enrolled in the pivotal phase. In the pivotal cohort, 26% were symptomatic and 75% were asymptomatic. Acute device and technical success were 99% (140 of 141). By hierarchical analysis, the all-stroke rate in the pivotal group was 1.4% (2 of 141), stroke and death was 2.8% (4 of 141), and stroke, death and MI was 3.5% (5 of 141). One patient (0.7%) experienced postoperative hoarseness from potential Xth cranial nerve injury, which completely resolved at the 6-month follow-up visit. Conclusions The results of the ROADSTER trial demonstrate that the use of the ENROUTE Transcarotid NPS is safe and effective at preventing stroke during CAS. The overall stroke rate of 1.4% is the lowest reported to date for any prospective, multicenter clinical trial of CAS.
Objectives In the Single Ventricle Reconstruction trial, infants undergoing the Norwood procedure were randomly allocated to undergo a right ventricle-to-pulmonary artery shunt or a modified ...Blalock-Taussig shunt. Apart from shunt type, subjects received the local standard of care. We evaluated variation in perioperative care during the Norwood hospitalization across 14 trial sites. Methods Data on preoperative, operative, and postoperative variables for 546 enrolled subjects who underwent the Norwood procedure were collected prospectively on standardized case report forms, and variation across the centers was described. Results Gestational age, birth weight, and proportion with hypoplastic left heart syndrome were similar across sites. In contrast, all recorded variables related to preoperative care varied across centers, including fetal diagnosis (range, 55%-85%), preoperative intubation (range, 29%-91%), and enteral feeding. Perioperative and operative factors were also variable across sites, including median total support time (range, 74-189 minutes) and other perfusion variables, arch reconstruction technique, intraoperative medication use, and use of modified ultrafiltration (range, 48%-100%). Additional variation across centers was seen in variables related to postoperative care, including proportion with an open sternum (range, 35%-100%), median intensive care unit stay (range, 9-44 days), type of feeding at discharge, and enrollment in a home monitoring program (range, 1%-100%; 5 sites did not have a program). Overall, in-hospital death or transplant occurred in 18% (range across sites, 7%-39%). Conclusions Perioperative care during the Norwood hospitalization varies across centers. Further analysis evaluating the underlying causes and relationship of this variation to outcome is needed to inform future studies and quality improvement efforts.
Although scleroderma-associated interstitial lung disease (SSc-ILD) is a significant contributor to both morbidity and mortality, its pathogenesis is largely unclear. Pulmonary function tests and ...high-resolution computed tomographic scanning continue to be the most effective tools to screen for lung involvement and to monitor for disease progression. More research and better biomarkers are needed to identify patients most at risk for developing SSc-ILD as well as to recognize which of these patients will progress to more severe disease. Although immunosuppression remains the mainstay of treatment, antifibrotic agents may offer new avenues of treatment for patients with SSc-ILD in the future.
Background Prompt correction of severe hyponatremia is important, but correction also must be limited to avoid iatrogenic osmotic demyelination. Expert opinion recommends that serum sodium level not ...be increased by more than 10-12 mEq/L in any 24-hour period and/or 18 mEq/L in any 48-hour period. However, inadvertent overcorrection is common, usually caused by the unexpected emergence of a water diuresis. Study Design Quality improvement report. Setting & Participants All 25 patients admitted to a community teaching hospital between October 1, 2008, and September 30, 2011, who were treated for serum sodium level <120 mEq/L with concurrently administered desmopressin and hypertonic saline solution. Quality Improvement Plan Concurrently administered desmopressin (1-2 µg parenterally every 6-8 hours) and hypertonic saline with weight-based doses adjusted to increase the serum sodium concentration by 6 mEq/L, avoiding inadvertent overcorrection of severe hyponatremia. Outcomes Rate of correction of hyponatremia, predictability of response to the combination, adverse events related to therapy. Measurements Rate of correction of hyponatremia at 4, 24, and 48 hours; administered dose of 3% saline solution, salt tablets, and potassium; predicted increase in serum sodium level. Results Mean changes in serum sodium levels during the first and second 24 hours of therapy were 5.8 ± 2.8 (SD) and 4.5 ± 2.2 mEq/L, respectively, without correction by >12 mEq/L in 24 hours or >18 mEq/L in 48 hours and without a decrease during therapy. There was no significant difference between actual and predicted increases during the first 24 hours. There was no adverse effect associated with therapy. Limitations Without concurrent controls, we cannot be certain that outcomes are improved. Balance studies were not performed. Conclusions Combined 3% saline solution and desmopressin appears to be a valid strategy for correcting severe hyponatremia, but studies comparing the regimen with other therapeutic strategies are needed.
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