Acute Kidney Injury Resulting From Hemoglobinuria After Pulsed-Field Ablation in Atrial Fibrillation: Is it Preventable?

BACKGROUND: High-voltage pulses can cause hemolysis. OBJECTIVES: The authors evaluated the occurrence of hemoglobinuria after pulsed-field ablation (PFA) and its impact on renal function in patients with atrial fibrillation (AF). METHODS: A consecutive series of patients with AF undergoing PFA were included in this analysis. The initial patients who did not receive postablation hydration immediately after the procedure were classified as group 1 (n = 28), and the rest of the study patients who received planned fluid infusion (0.9% sodium chloride ≥2 L) after the procedure were categorized as group 2 (n = 75). RESULTS: Of the 28 patients in group 1, 21 (75%) experienced hemoglobinuria during the 24 hours after catheter ablation. The mean postablation serum creatinine (S-Cr) was significantly higher than the baseline value in those 21 patients (1.46 ± 0.28 mg/dL vs 0.86 ± 0.24 mg/dL, P < 0.001). Of those 21 patients, 4 (19%) had S-Cr. >2.5 mg/dL (mean: 2.95 ± 0.21 mg/dL). The mean number of PF applications was significantly higher in those 4 patients than in the other 17 patients experiencing hemoglobinuria (94.63 ± 3.20 vs 46.75 ± 9.10, P < 0.001). In group 2 patients, no significant changes in S-Cr were noted. The group 2 patients received significantly higher amounts of fluid infusion after catheter ablation than did those in group 1 (2,082.50 ± 258.08 mL vs 494.01 ± 71.65 mL, P < 0.001). In multivariable analysis, both hydration (R2 = 0.63, P < 0.01) and number of PFA applications (R2 = 0.33, P < 0.01) were independent predictors of postprocedure acute kidney injury. CONCLUSIONS: On the basis of our findings, both the number of PFA applications and postablation hydration were independent predictors of renal insult that could be prevented using planned fluid infusion immediately after the procedure.

Multicenter experience with andexanet alfa for refractory pericardial bleeding during catheter ablation of atrial fibrillation.

INTRODUCTION: Pericardial bleeding is a rare but life-threatening complication of atrial fibrillation (AF) ablation. Patients taking uninterrupted oral anticoagulation (AC) may be at increased risk for refractory bleeding despite pericardiocentesis and administration of protamine. In such cases, andexanet alfa can be given to reverse rivaroxaban or apixaban. In this study, we aim to describe the rate of acute hemostasis and thromboembolic complications with andexanet for refractory pericardial bleeding during AF ablation. METHODS AND RESULTS: In this multicenter, case series, participating centers identified patients who received a dose of apixaban or rivaroxaban within 24 h of AF ablation, developed refractory pericardial bleeding during the procedure despite pericardiocentesis and administration of protamine and received andexanet. Eleven patients met inclusion criteria, with mean age of 73.5 ± 5.3 years and median CHA2 DS2 -VASc score 4 [3-5]. All patients received protamine and pericardiocentesis, and 9 (82%) received blood products. All patients received a bolus of andexanet followed, in all but one, by a 2-h infusion. Acute hemostasis was achieved in eight patients (73%) while three required emergent surgery. One patient (9%) experienced acute ST-elevation myocardial infarction after receiving andexanet. Therapeutic AC was restarted after a mean of 2.2 ± 1.9 days and oral AC was restarted after a mean of 2.9 ± 1.6 days, with no recurrent bleeding. CONCLUSION: In patients on uninterrupted apixaban or rivaroxaban, who develop refractory pericardial bleeding during AF ablation, andexanet can achieve hemostasis thereby avoiding the need for emergent surgery. However, there is a risk of thromboembolism following administration.

Various Manifestations of 5-Fluorouracil Cardiotoxicity: A Multicenter Case Series and Review of Literature.

5-Fluorouracil is a key element to the treatment of colon cancer. But it is also one of the most cardiotoxic chemotherapies, and the management of those that experience cardiotoxicity can be challenging. We present three cases of 5-FU cardiac toxicity that manifested as myocardial infarction, cardiogenic shock, and ventricular fibrillation. Additionally, we discuss the current literature regarding 5-fluorouracil cardiotoxicity mechanisms as well as management.

The analysis of gun-cleaning oil as long-distance gunshot residue and its implications for chemical tags on bullets.

Using a BB gun, it was shown that a gun-cleaning oil (GCO) can be wiped from the barrel by a projectile and carried much longer distances than those usually associated with solid gunshot residue (GSR). Analysis of GCO subsequently deposited on a target was performed using pentane extraction and gas chromatography. (Hoppe's GCO was used here as a model.) When a 0.45 caliber handgun was used, analysis reveals that most of the GCO wiped from the barrel does not survive, owing to the elevated temperatures encountered. However, two components of the GCO, a long-chain fatty acid and its ethyl ester, do survive and can be detected in the bullet wipe. This suggests that GCO may be considered as GSR, uniquely detectable at long distances, and that other chemical compounds could either be added to a GCO or directly to bullets, to serve as identifying chemical tags.

Determination of pyridoxal-5'-phosphate (PLP)-bonding sites in proteins: a peptide mass fingerprinting approach based on diagnostic tandem mass spectral features of PLP-modified peptides.

Peptides modified by pyridoxal-5'-phosphate (PLP), linked to a lysine residue via reductive amination, exhibit distinct spectral characteristics in the collision-induced dissociation (CID) tandem mass (MS/MS) spectra that are described here. The MS/MS spectra typically display two dominant peaks whose m/z values correspond to neutral losses of [H3PO4] (-98 Da) and the PLP moiety as [C8H10NO5P] (-231 Da) from the precursor peptide ion, respectively. Few other peaks are observed. Recognition of this distinct fragmentation behavior is imperative since determining sequences and sites of modifications relies on the formation of amide backbone cleavage products for subsequent interpretation via proteome database searching. Additionally, PLP-modified peptides exhibit suppressed precursor ionization efficiency which diminishes their detection in complex mixtures. Presented here is a protocol which describes an enrichment strategy for PLP-modified peptides combined with neutral loss screening and peptide mass fingerprinting to map the PLP-bonding site in a known PLP-dependent protein. This approach represents an efficient alternative to site-directed mutagenesis which has been the traditional method used for PLP-bonding site localization in proteins.

Cryolipolysis for noninvasive fat cell destruction: initial results from a pig model.

BACKGROUND: Liposuction is one of the most frequently performed cosmetic procedures in the United States, but its cost and downtime has led to the development of noninvasive approaches for adipose tissue reduction. OBJECTIVE: To determine whether noninvasive controlled and selective destruction of fat cells (Cryolipolysis) can selectively damage subcutaneous fat without causing damage to the overlying skin or rise in lipid levels. METHODS: Three Yucatan pigs underwent Cryolipolysis at 22 sites: 20 at cooling intensity factor (CIF) index 24.5 (-43.8 mW/cm(2)), one at CIF 24.9 (-44.7 mW/cm(2)), and one at CIF 25.4 (-45.6 mW/cm(2)). Treated areas were evaluated using photography, ultrasound, and gross and microscopic pathology. Lipids were at various times points. One additional pig underwent Cryolipolysis at various days before euthanasia. RESULTS: The treatments resulted in a significant reduction in the superficial fat layer without damage to the overlying skin. An inflammatory response triggered by cold-induced apoptosis of adipocytes preceded the reduction in the fat layer. Evaluation of lipids over a 3-month period following treatment demonstrated that cholesterol and triglyceride values remained normal. CONCLUSIONS: Cryolipolysis is worthy of further study because it has been shown to significantly decrease subcutaneous fat and change body contour without causing damage to the overlying skin and surrounding structures or deleterious changes in blood lipids.

Clinical efficacy of noninvasive cryolipolysis and its effects on peripheral nerves.

BACKGROUND: Cryolipolysis provides a method for noninvasive fat reduction that significantly reduces subcutaneous fat in a pig model without apparent damage to skin and surrounding structures. This study aimed to determine whether fat reduction in humans caused by cold exposure is associated with alteration in local sensory function or nerve fibers. METHODS: In this study, 10 subjects were treated with a prototype cooling device. Fat reduction was assessed in 9 of the 10 subjects via ultrasound before treatment and at the follow-up visit. Sensory function was assessed by neurologic evaluation (n = 9), and biopsies (n = 1) were collected for nerve staining. RESULTS: Treatment resulted in a normalized fat layer reduction of 20.4% at 2 months and 25.5% at 6 months after treatment. Transient reduction in sensation occurred in six of nine subjects assessed by neurologic evaluation. However, all sensation returned by a mean of 3.6 weeks after treatment. Biopsies showed no long-term change in nerve fiber structure. There were no lasting sensory alterations or observations of skin damage in any of the subjects evaluated. CONCLUSION: Noninvasive cryolipolysis results in substantial fat reduction within 2 months of treatment without damage to skin. The procedure is associated with modest reversible short-term changes in the function of peripheral sensory nerves.

Temporal patterns of postoperative complications.

HYPOTHESIS: A variety of major complications occur after intra-abdominal operations. Knowledge of when specific complications occur during the postoperative period would be useful in their diagnosis, prevention, and management. Our aim was to determine the incidence of major complications during specific postoperative intervals. DESIGN: One thousand twenty-one patients undergoing intra-abdominal operations were studied postoperatively as part of a randomized clinical trial. Thirteen defined major complications were sought at the following specific intervals: less than 1, 1 through 3, 4 through 7, and 8 through 30 days after the operation. SETTING: Cooperative trial from 15 Veterans Affairs medical centers. INTERVENTIONS: Intra-abdominal aortic, gastric, biliary, and colonic procedures. MAIN OUTCOME MEASUREMENTS: Major postoperative complications. RESULTS: Four hundred thirty-five major complications were diagnosed within 30 days of the patients' being operated on. Seventy-four (17%) occurred within 1 day, 185 (43%) between 1 and 3 days, 72 (17%) between 4 and 7 days, and 104 (24%) between 8 and 30 days. Three deaths (8%) occurred within 1 day, 3 (8%) in 1 through 3 days, 4 (11%) in 4 through 7 days, and 27 (73%) in 8 through 30 days. The greatest risk of hypotension (43%), myocardial infarction (47%), and respiratory depression (55%) was within 1 day. The highest incidence of congestive heart failure (46%), pulmonary embolus (50%), and respiratory failure (76%) occurred at 1 through 3 days. Pneumonia (38%) was most common at 4 through 7 days. Cerebrovascular accident (53%) and sepsis (71%) occurred preponderantly at 8 through 30 days. Renal failure had a bimodal distribution with maxima at 1 through 3 days (31%) and 8 through 30 days (56%). The risk of cardiac arrhythmia and gastrointestinal tract bleeding was similar throughout all intervals. CONCLUSIONS: While major complications occur throughout the postoperative period, the highest incidence is 1 through 3 days after the operation. However, specific complications occur in the following distinct temporal patterns: early postoperative, several days after the operation, throughout the postoperative period, and in the late postoperative period. Knowledge of these patterns should aid clinical management.

Additives for the stabilization of double-stranded DNA in UV-MALDI MS.

Molecular complexes such as double-stranded oligonucleotides contain non-covalent bonds that are difficult to maintain in the MALDI experiment. Quantifiers are introduced in order to evaluate, summarize, and compare spectra from experiments in which additives are used to stabilize duplex oligonucleotides. Compounds known to complex with and stabilize duplex molecules can be useful as additives in MALDI. Spermine and methylene blue, present at concentrations similar to the matrix, are detected, bound to the duplex. When peptides are used as additives, the duplex is stabilized when the peptide is present at an amount less than that of the duplex.