Comparison of cerebral safety after atrial fibrillation using pulsed field and thermal ablation: Results of the neurological assessment subgroup in the ADVENT trial.

BACKGROUND: Atrial fibrillation (AF) ablation carries the risk of silent cerebral event (SCE) and silent cerebral lesion (SCL). Although "silent," these may have long-term clinical implications and are challenging to study as postprocedural magnetic resonance imaging (MRI) is not standard of care. OBJECTIVE: The neurological assessment subgroup (NAS) of ADVENT compared cerebral effects of pulsed field ablation (PFA) with standard-of-care thermal ablation. METHODS: The NAS included consecutive randomized PFA and thermal ablation patients who received postprocedural brain MRI 12-48 hours after ablation. Patients with apparent SCE or SCL findings underwent a modified Rankin scale assessment. MRI images were subsequently reviewed by a blinded brain imaging core laboratory. RESULTS: In total, 77 patients with paroxysmal AF were enrolled at 6 centers; 71 had analyzable scans (34 PFA; 37 thermal ablation). Through individual center review, 6 PFA and 4 thermal scans were identified as SCE/SCL positive, of which 3 PFA and 0 thermal SCE/SCL findings were confirmed by a blinded core laboratory. MRI findings revealed 1 patient with 2- to 4-mm SCEs, 1 patient with a 3-mm SCE, and 1 patient with 2 SCLs (5.5 mm and 11 mm). All modified Rankin scale and National Institutes of Health Stroke Scale scores were 0 before discharge and at 90-day follow-up. There were only 2 neurological safety events (1 transient ischemic attack [PFA] and 1 stroke [thermal ablation]) in the ADVENT study, neither of which was part of the NAS. CONCLUSION: The ADVENT trial provides the first prospective, randomized data on the cerebral impact of PFA and thermal ablation of AF. Incidence of SCE/SCL after ablation in the NAS was low.

Point-of-Care Ultrasound in the Emergency Department: Training, Perceptions, Applications, and Barriers from Different Healthcare Professionals.

Background: Point-of-care ultrasound (POCUS) is a valuable tool that assists in diagnosis and management of patients in the emergency department (ED) while being cost-efficient and without the use of ionizing radiation. To discern the opinions and perceptions of ED staff about POCUS applications and barriers, we conducted a cross-sectional survey of employees of 12 EDs in North Texas. Methods: Participants completed a 20-item online survey about POCUS with questions pertaining to four domains: (1) employee and training information, (2) perceived benefits, (3) common applications, and (4) barriers to use. Out of 805 eligible ED employees, 103 completed the survey (16.1% response rate). Results: The results indicated a generally positive perception of POCUS among all employee types. Physician had significant exposure and training of POCUS than non-physician group ( p < 0.001). Physicians tend to find cardiac assessments more useful for clinical management than non-physicians (47% vs. 23%, p = 0.01), while non-physicians find soft tissue/abscess assessments more useful (27% vs. 9%, p = 0.01). Conclusion: The most significant barriers to POCUS use were time constraints for physicians and a lack of training for non-physician employees. Our study provides valuable insights into the perceptions of multiple ED professionals, serving as a foundation for promoting POCUS use in the ED.

Broadening Perspectives of Artificial Intelligence in Echocardiography.

Echocardiography frequently serves as the first-line treatment of diagnostic imaging for several pathological entities in cardiology. Artificial intelligence (AI) has been growing substantially in information technology and various commercial industries. Machine learning (ML), a branch of AI, has been shown to expand the capabilities and potential of echocardiography. ML algorithms expand the field of echocardiography by automated assessment of the ejection fraction and left ventricular function, integrating novel approaches such as speckle tracking or tissue Doppler echocardiography or vector flow mapping, improved phenotyping, distinguishing between cardiac conditions, and incorporating information from mobile health and genomics. In this review article, we assess the impact of AI and ML in echocardiography.

Echocardiography is the most common test in cardiovascular imaging and helps diagnose multiple different diseases. Machine learning, a branch of artificial intelligence (AI), will reduce the workload for medical professionals and help improve clinical workflows. It can rapidly calculate a lot of important cardiac parameters such as the ejection fraction or important metrics during different phases of the cardiac cycle. Machine learning algorithms can include new technology in echocardiography such as speckle tracking, tissue Doppler echocardiography, vector flow mapping, and other approaches in a user-friendly manner. Furthermore, it can help find new subtypes of existing diseases in cardiology. In this review article, we look at the current role of machine learning and AI in the field of echocardiography.

Pulmonary vein narrowing after pulsed field versus thermal ablation.

AIMS: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation. METHODS AND RESULTS: ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation-force-sensing RF or cryoballoon (CB)-to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (-0.9%) than thermal ablation (-12%, posterior probability > 0.999)-primarily driven by the RF sub-cohort (-19.5%) vs. CB sub-cohort (-3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location. CONCLUSION: In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing-thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue.

Validation of a Deep Learning Algorithm for Continuous, Real-Time Detection of Atrial Fibrillation Using a Wrist-Worn Device in an Ambulatory Environment.

BACKGROUND: Wearable devices may be useful for identification, quantification and characterization, and management of atrial fibrillation (AF). To date, consumer wrist-worn devices for AF detection using photoplethysmography-based algorithms perform only periodic checks when the user is stationary and are US Food and Drug Administration cleared for prediagnostic uses without intended use for clinical decision-making. There is an unmet need for medical-grade diagnostic wrist-worn devices that provide long-term, continuous AF monitoring. METHODS AND RESULTS: We evaluated the performance of a wrist-worn device with lead-I ECG and continuous photoplethysmography (Verily Study Watch) and photoplethysmography-based convolutional neural network for AF detection and burden estimation in a prospective multicenter study that enrolled 117 patients with paroxysmal AF. A 14-day continuous ECG monitor (Zio XT) served as the reference device to evaluate algorithm sensitivity and specificity for detection of AF in 15-minute intervals. A total of 91 857 intervals were contributed by 111 subjects with evaluable reference and test data (18.3 h/d median watch wear time). The watch was 96.1% sensitive (95% CI, 92.7%-98.0%) and 98.1% specific (95% CI, 97.2%-99.1%) for interval-level AF detection. Photoplethysmography-derived AF burden estimation was highly correlated with the reference device burden (R2=0.986) with a mean difference of 0.8% (95% limits of agreement, -6.6% to 8.2%). CONCLUSIONS: Continuous monitoring using a photoplethysmography-based convolutional neural network incorporated in a wrist-worn device has clinical-grade performance for AF detection and burden estimation. These findings suggest that monitoring can be performed with wrist-worn wearables for diagnosis and clinical management of AF. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04546763.

Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known. METHODS: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events. RESULTS: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999). CONCLUSIONS: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.).

Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms.

The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and neonatal immunity. Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions and Fc receptor-binding after Ad26.COV2.S compared to mRNA vaccination and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccines have higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination results in enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition relative to second trimester. Higher transplacental transfer ratios following first and second trimester vaccination may reflect placental compensation for waning maternal titers. These results provide novel insight into the impact of platform and trimester of vaccination on maternal humoral immune response and transplacental antibody transfer.

Clinical Characteristics of Patients Returning to Emergency Department With Initial False-Negative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Based COVID-19 Test.

Background: The coronavirus disease 2019 (COVID-19) outbreak is an international public health emergency. Early identification of COVID-19 patients with false-negative RT-PCR tests is paramount in the ED to prevent both nosocomial and community transmission. This study aimed to compare clinical characteristics of repeat emergency department (ED) visits among coronavirus disease 2019 (COVID-19) patients with initial false-negative reverse transcriptase-polymerase chain reaction (RT-PCR)-based COVID-19 test. Methods: This is a retrospective, multi-center, cohort study conducted at 12 hospitals affiliated with Baylor Scott & White Health system. Patients visiting the EDs of these hospitals between June and August 2020 were screened. Patients tested negative for viral RNA by quantitative RT-PCR in the first ED visit and positive in the second ED visit were included. The primary outcome was the comparison of clinical characteristics between two consecutive ED visits including the clinical symptoms, triage vital signs, laboratory, and chest X-ray (CXR) results. Results: A total of 88 confirmed COVID-19 patients with initial false-negative RT-PCR COVID-19 test in the ED were included in the final analyses. The mean duration of symptoms in the second ED visit was significantly higher (3.6 ± 0.4 vs. 2.6 ± 0.3 days, p = 0.020). In the first ED visit, lymphocytopenia (35.2%), fever (32.6%), nausea (29.5%), and dyspnea (27.9%) are the most common signs of COVID-19 infection during the window period. There were significant increases in the rate of hypoxia (13.6% vs. 4.6%, p = 0.005), abnormal infiltrate on CXR (59.7% vs. 25.9%, p < 0.001), and aspartate aminotransferase (AST) elevation (26.1% vs. 9.1%, p < 0.001) in the second ED visit. Conclusions: Early COVID-19 testing (less than 3 days of symptom duration) could be associated with a false-negative result. In this window period, lymphocytopenia, fever, nausea, and dyspnea are the most common early signs that can potentially be clinical hints for COVID-19 diagnosis.

Rhabdomyolysis-induced acute kidney injury in a patient with non-compliance to levothyroxine therapy.

SUMMARY: Hypothyroidism is a common medical condition and is often easily managed with excellent outcomes, when treated adequately. Compliance with levothyroxine (LT4) therapy is often compromised because of the need for a daily and lasting schedule. Overt rhabdomyolysis due to under-treatment or non-compliance is a rare occurrence. We report a case of rhabdomyolysis leading to acute kidney injury (AKI) on chronic kidney disease (CKD) requiring hemodialysis (HD) in a 68-year-old Caucasian male due to non-compliance with levothyroxine (LT4) therapy. Our patient 'ran out of levothyroxine' for approximately 4 weeks and developed gradually progressive muscle pain. The diagnosis of severe AKI due to rhabdomyolysis was made based on oliguria, elevated creatinine kinase (CK), and renal failure. Resuming the home dose of LT4 failed to correct CK levels, and there was a progressive decline in renal function. Although increasing doses of LT4 and three cycles of HD improved CK levels, they remained above baseline at the time of discharge. The patient recovered gradually and required HD for 4 weeks. CK levels normalized at 6 weeks. Through this case report, we highlight that non-compliance with LT4 therapy can lead to life-threatening complications such as renal failure and hence the need to educate patients on the significance of compliance with LT4 therapy should be addressed. LEARNING POINTS: Non-compliance to levothyroxine therapy is common and can lead to serious complications, including rhabdomyolysis. Rhabdomyolysis is an uncommon presentation of hypothyroidism and severe rhabdomyolysis can result in renal failure requiring hemodialysis. Rhabdomyolysis associated with hypothyroidism can be further exacerbated by concomitant use of statins.

Malnutrition-Inflammation Complex Syndrome: A Cause of Low Parathyroid Hormone in Patients With Chronic Kidney Disease.

Secondary hyperparathyroidism is commonly seen in patients with chronic kidney disease (CKD) due to hypocalcemia, hyperphosphatemia and low vitamin D levels and is associated with high-turnover bone disease. In contrast, some patients with advanced CKD, including those requiring dialysis (end-stage renal disease [ESRD]), develop adynamic bone disease with features of low-turnover bone disease. Low serum parathyroid hormone (PTH) has been used as a biochemical marker of adynamic bone disease. Low PTH levels may not necessarily be due to adynamic bone disease but could be a manifestation of the malnutrition inflammation complex syndrome (MICS). The optimal management of hypoparathyroidism associated with MICS is not well known. Currently, there is insufficient evidence to suggest if there is any role in improving nutritional and inflammatory status among patients with CKD and MICS. Furthermore, it also remains unclear whether these changes will help address low PTH levels seen in these patients. We report three patients with advanced CKD who had very low PTH levels possibly attributed to MICS. In addition, we briefly discuss other characteristics and pathophysiology of MICS.

Trends and effect of atrial fibrillation on inpatient outcomes after transcatheter aortic valve replacement.

BACKGROUND: Atrial fibrillation (AF) is common in patients undergoing transcatheter aortic valve replacement (TAVR) but there is conflicting evidence on whether AF impacts outcomes after TAVR. METHODS: Hospitalizations of adults ≥50 years old who had undergone elective TAVR from 2012 to 2015 were included. Poisson regression was used to assess changes in in-hospital complications, average length of stay (LOS) after TAVR, and discharge disposition over time. Multivariable logistic, linear, and generalized logistic regression models, adjusting for patient and hospital characteristics, were used to estimate the effect of AF on inpatient outcomes. RESULTS: A total of 7,266 TAVR hospitalizations were included; AF was present in 44% of patients. Between 2012 and 2015, there was a significant decrease in the incidence of acute kidney injury, blood transfusion, average LOS, and inpatient mortality both for AF and non-AF patients. However, the incidences of vascular complications and major bleeding decreased only among non-AF patients. After adjustment, AF was associated with increased incidences of TIA/stroke (OR 1.36, 95% CI: 1.01, 1.85), acute kidney injury (OR 1.54, 95% CI: 1.33, 1.78), blood transfusion (OR 1.14, 95% CI: 1.00, 1.30), transfer to a skilled nursing facility (OR 1.38, 95% CI: 1.23, 1.55), and longer average LOS (CIE 1.30, 95% CI: 1.06, 1.54). AF was not associated with inpatient mortality (OR 1.09, 95% CI: 0.81, 1.48). CONCLUSIONS: AF is prevalent among patients undergoing TAVR, and is associated with higher incidences of inpatient complications, discharge to a skilled nursing facility, and longer average LOS. While the incidence of many complications has declined in the past few years, continued efforts to further reduce complications in patients with AF is urgently required for expansion of TAVR to broader populations.

Progression in the severity of aortic stenosis according to race among those with advanced chronic kidney disease.

BACKGROUND: There is a higher prevalence of aortic stenosis (AS) in patients with advanced chronic kidney disease (CKD) and European ancestry. However, studies comparing AS progression in white and black patients in an advanced CKD population do not exist. METHODS: Advanced CKD (stage IV-V) patients who were referred to the UNC Cardiorenal Clinic for pre-operative kidney transplant evaluation, and diagnosed with either AS (mild, moderate, or severe) or a left ventricular outflow tract velocity ≥2 m/s at any point between 2006-2016 were eligible for inclusion. Serial transthoracic echocardiograms over the 10-year period determined AS progression. All echocardiograms acquired after renal transplantation or aortic valve replacement were excluded. The rates of change of three indices of AS severity [mean gradient, aortic valve area (AVA), and aortic valve velocity] were compared between white and black patients. Mixed effects linear models with repeated measures were used to estimate the overall and race-stratified yearly rate of progression for each index, adjusted for age, sex, smoking status, dialysis, and baseline cholesterol. RESULTS: Of 1,283 patients, 140 (34% white, 66% black) developed or had baseline AS. Initially, 81% had no AS, 13% had mild, and 6% had moderate. White patients were more likely to be male and less likely to be on hemodialysis compared to black patients. No differences in AS severity (P=0.55) or age (60 vs. 58 years, P=0.34) were seen at baseline. In white vs. black patients, mean gradient increased at 1.90 (95% CI: 0.79, 3.01) mmHg/year vs. 1.46 (95% CI, 0.79, 2.14) mmHg/year, P=0.20, AVA decreased at -0.10 (95% CI: -0.15, -0.05) m2/year vs. -0.08 (95% CI: -0.11, -0.05) m2/year, P=0.13, and transvalvular velocity increased at 0.11 (95% CI: 0.04, 0.18) m/s/year vs. 0.07 (95% CI: 0.03, 0.11) m/s/year, P=0.09. CONCLUSIONS: Compared to black patients, white patients in an advanced CKD cohort may have exhibited more rapid progression of AS. Ours is the first study to analyze racial differences in such a population. A study with a larger sample size is needed to confirm our findings.

Impact of age and comorbidities on the effect of transcatheter versus surgical mitral valve repair on inpatient outcomes.

BACKGROUND: Transcatheter mitral valve repair (TMVR) has shown to be a safe and effective treatment option for symptomatic severe mitral regurgitation (MR) in patients who are at prohibitive surgical risk. Whether age and comorbidities impact the inpatient safety outcomes of TMVR versus surgical mitral valve repair (SMVR) is unknown. METHODS: Using the national inpatient sample, patients undergoing either elective TMVR or SMVR between 2012 and 2015 were analyzed. Logistic, generalized logistic, and linear regression were used to compare inpatient complications, discharge disposition, and length of stay (LOS). Heterogeneity in the effect of TMVR versus SMVR across Charlson comorbidity index (CCI, categorized as <2 and ≥2) and age (categorized as <75 years old and ≥75 years old) were assessed for effect modification. RESULTS: Overall, 8,716 hospitalizations were included, 7,950 (91%) SMVR and 766 (9%) TMVR. Compared with SMVR, patients undergoing TMVR were older (median age 79 vs. 62 years) and more likely to be female (45% vs. 40%) with a higher CCI score (median CCI 2 vs. 1). Despite being older with a higher comorbidity burden, patients undergoing TMVR had a lower incidence of permanent pacemaker implantation (OR 0.23, 95% CI: 0.11, 0.50), cerebrovascular accidents (OR 0.37, 95% CI: 0.15, 0.92), and major bleeding (OR 0.39, 95% CI: 0.32, 0.47). TMVR patients were also discharged 3 days earlier (CIE -3.26; 95% CI: -3.72, -2.80) and were less likely to be discharged to a skilled nursing facility (OR 0.72, 95% CI 0.55, 0.93). Additionally, the relative reduction in complications after TMVR versus SMVR was significantly higher in older (age ≥75 years) and more comorbid (CCI ≥2) patients (p for interaction <.05 for both). CONCLUSION: Patients treated with TMVR, as compared with SMVR, were older and had more comorbidities, but had a lower incidence of inpatient complications, shorter LOS, and better discharge disposition. Therefore, TMVR may be a safer option than SMVR in older patients and those with a higher burden of comorbidities.

Vaccine-associated kidney diseases: A narrative review of the literature.

Immunization is one of the greatest public health achievements of the 20th century. Vaccines have enabled the eradication of deadly diseases and decreased the morbidity and mortality associated with various infections. Most vaccines are safe to administer and cause only minor side effects. Although very rare, various glomerular diseases and acute kidney injury have been reported following immunization with certain vaccines including influenza, pneumococcal, and hepatitis B vaccines. This review summarizes these rare renal complications that have been published in the literature. Physicians and other health-care providers administrating vaccines should be aware of these very rare but possible renal side effects.

Sitagliptin and Simvastatin Interaction Causing Rhabdomyolysis and AKI.

We report a case of rhabdomyolysis and severe acute kidney injury (AKI) requiring dialysis in a 69-year-old male who was recently started on sitagliptin while on chronic simvastatin therapy. This potential interaction is not included in the package insert for sitagliptin. A comprehensive literature review revealed six previous reports of rhabdomyolysis due to drug interaction between sitagliptin and statins including simvastatin, lovastatin, and atorvastatin. Of these six cases, only two had developed rhabdomyolysis-associated AKI, none of which were severe enough to require dialysis. As patients are commonly prescribed statins and sitagliptin for treatment of dyslipidemia and diabetes, health care professionals should be aware of this potential drug interaction and closely monitor their patients for signs and symptoms of rhabdomyolysis and AKI. This case highlights the importance of conducting further studies on the risk of muscular toxicity of sitagliptin especially when administered concurrently with statins.

Acute Uric Acid Nephropathy following Epileptic Seizures: Case Report and Review.

Acute hyperuricemia most commonly occurs in patients who experience tumor lysis syndrome. Hyperuricemia along with other electrolyte abnormalities like hyperkalemia, hypocalcemia, and hyperphosphatemia leads to acute kidney injury (AKI) due to acute uric acid nephropathy which is associated with significant morbidity. High risk patients are thus closely monitored for signs of these laboratory abnormalities. Extreme exercise, rhabdomyolysis, and seizures are rare causes of acute hyperuricemia. Serum uric acid level is not routinely monitored as a part of postictal labs. We report an unusual case of AKI in a young male with recurrent seizures and no associated rhabdomyolysis who was found to have acute uric acid nephropathy. Timely administration of Rasburicase prevented the need for dialysis in this patient and led to complete renal recovery. This case illustrates the importance of doing a urine microscopy and checking uric acid level in patients with recurrent seizures who develop unexplainable AKI, as timely management helps improve outcome. We also briefly review the pathophysiology of seizure related hyperuricemia and acute uric acid nephropathy.

Membranous nephropathy and severe acute kidney injury following influenza vaccination.

Immunization with influenza vaccine remains an important global health strategy to prevent outbreaks and epidemics of seasonal influenza. Influenza vaccine has rarely been associated with vasculitis, acute kidney injury (AKI) and nephrotic syndrome (NS). Glomerular diseases following influenza vaccination have also been rarely reported. We report a patient who developed acute-onset massive proteinuria with NS and severe AKI soon after receiving the 2009 H1N1 influenza vaccine. Kidney biopsy showed membranous nephropathy (MN) and acute interstitial nephritis (AIN). Optimal management of glomerular diseases or AIN following influenza vaccination is not known. Our patient responded well to an initial course of oral corticosteroid therapy with normalization of serum creatinine level but had a relapse of NS with AKI soon after completion of corticosteroid therapy. A repeat kidney biopsy revealed MN and resolved AIN. A subsequent prolonged course of oral corticosteroids resulted in complete clinical remission of the NS as well as normalization of renal function. Long-term response to corticosteroid therapy in such cases is not known. However, our patient continued to remain in clinical remission with normal renal function, five years after the initial treatment.

Mexiletine Prevents Recurrent Torsades de Pointes in Acquired Long QT Syndrome Refractory to Conventional Measures.

OBJECTIVES: The purpose of this study was to examine the role of mexiletine, a late sodium current (INa-L) blocker, in acute termination of torsades de pointes (TdP) refractory to conventional therapy in acquired long QT syndromes (LQTS). BACKGROUND: Long QT interval can predispose to TdP and is therefore associated with significant mortality. Currently, there is no available pharmacotherapy to target directly the ionic basis of most LQTS for the acute termination of TdP. Earlier evidence highlighted the role of INa-L in the pathophysiology of long QT and TdP, particularly in patients with congenital LQTS. METHODS: Twelve patients with TdP caused by acquired LQTS were treated with mexiletine after failure of conventional treatment including discontinuation of QT-prolonging drugs, intravenous administration of magnesium, and correction of serum electrolyte abnormalities. RESULTS: No recurrence of TdP occurred within 2 h after initiation of treatment with mexiletine in all 12 patients. Macro T-wave alternans accompanied by QT prolongation, an electrocardiographic precursor of TdP that was seen in 3 patients, was also abolished by mexiletine. Treatment with mexiletine shortened the QTc interval from 599 ± 27 ms to 514 ± 16 ms (p = 0.001). The interval from the peak to the end of the T-wave (Tp-e interval) decreased from 145 ± 18 ms to 106 ± 9 ms (p = 0.005). The Tp-e/QT ratio decreased from 0.27 ± 0.02 to 0.23 ± 0.018 (p = 0.01). Mexiletine had no significant effect on QRS complex duration. CONCLUSIONS: INa-L blockade with mexiletine may be an effective treatment approach to terminate refractory TdP from several acquired causes of LQTS.

Glomerular diseases associated with cancer, chemotherapy, and hematopoietic stem cell transplantation.

Many solid and hematological malignancies have been associated with different glomerular diseases. Several case reports and case series of cancer-associated glomerular diseases have shown that treating the cancer may lead to resolution of the glomerular process. Hence, knowledge and approach to cancer-associated glomerular diseases is important for both the caring nephrologists and the cancer specialists. While membranous nephropathy has been classically associated with solid malignancies, minimal change disease has been commonly described with hematologic malignancies, especially non-Hodgkin's lymphoma. Membranoproliferative glomerulonephritis is increasingly being recognized to be associated with chronic hematologic malignancies such as chronic lymphocytic leukemia. In this article, we review various cancer-associated glomerular diseases and their pathogenesis as well as principles of treatment. In addition, we also review glomerular diseases seen after chemotherapy and hematopoietic stem cell transplantation.