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Background and Objectives: Patients with acute symptomatic seizures (ASyS) and acute epileptiform findings on EEG are common. They are often prescribed long-term antiseizure medications (ASMs); it is unknown whether or when this is necessary. Primary outcome was late unprovoked seizure occurrence and association with ASM taper. The secondary outcome was EEG pattern evolution over time., Methods: This is a retrospective cohort study of patients from 2015 to 2021 with ASyS (clinical or electrographic) and/or epileptiform findings on index hospitalization EEGs who were discharged on ASMs and had subsequent follow-up including an outpatient EEG at Yale New Haven Hospital. All patients were seen in our postacute symptomatic seizure (PASS) clinic after hospital discharge. We also developed a simple predictive score, Epilepsy-PASS (EPI-PASS), using variables independently associated with seizure recurrence based on stepwise regression; each of the 3 identified variables was assigned a score of 0 (absent) or 1 (present), for a total score of 0-3., Results: Of 190 patients screened, 58 were excluded, leaving a final cohort of 112 patients. Twenty-four percent (27/112) patients developed a late unprovoked seizure (i.e., epilepsy). Independent predictors of epilepsy were persistence of epileptiform abnormalities on follow-up EEGs [56% developed epilepsy vs 19% without, 0.002, OR 7.18 (1.36-37.88)], clinical ASyS [32% vs 13%, p = 0.002, OR 7.45 (2.31-54.36)], and cortical involvement on imaging [40% vs 11%, p = 0.003, OR 7.63 (1.96-29.58)]. None of the 23 patients with none of these predictors (0 points on EPI-PASS) developed epilepsy, vs 13% with 1 predictor (EPI-PASS = 1) and 46% with 2 or 3 predictors (EPI-PASS = 2-3) at 1-year follow-up. ASM taper was not associated with seizure recurrence. Abnormal EEG findings in the index hospitalization usually resolved [54/69 (78%) patients] on subsequent EEGs., Discussion: Most patients with clinical ASyS or acute epileptiform EEG findings do not require long-term ASMs. Index hospitalization EEG findings usually resolve, but if they do not, there is a >50% chance of developing epilepsy. Other predictors of epilepsy are cortical involvement on imaging and clinical ASyS. A simple 4-point scale using these 3 predictors (EPI-PASS) may help predict the risk of developing epilepsy but requires independent validation., Competing Interests: A. Sivaraju is a national co-PI for the PASSION (Post Acute Symptomatic Seizure Investigation and Outcomes Network) consortium; the other authors report no relevant disclosures; J.A. Kim has no relevant disclosures; E.J. Gilmore has no relevant disclosures; and L.J. Hirsch has no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

The ATR kinase protects cells against DNA damage and replication stress and represents a promising anti-cancer drug target. The ATR inhibitors (ATRi) berzosertib and gartisertib are both in clinical trials for the treatment of advanced solid tumors as monotherapy or in combination with genotoxic agents. We carried out quantitative phospho-proteomic screening for ATR biomarkers that are highly sensitive to berzosertib and gartisertib, using an optimized mass spectrometry pipeline. Screening identified a range of novel ATR-dependent phosphorylation events, which were grouped into three broad classes: (i) targets whose phosphorylation is highly sensitive to ATRi and which could be the next generation of ATR biomarkers; (ii) proteins with known genome maintenance roles not previously known to be regulated by ATR; (iii) novel targets whose cellular roles are unclear. Class iii targets represent candidate DNA damage response proteins and, with this in mind, proteins in this class were subjected to secondary screening for recruitment to DNA damage sites. We show that one of the proteins recruited, SCAF1, interacts with RNAPII in a phospho-dependent manner and recruitment requires PARP activity and interaction with RNAPII. We also show that SCAF1 deficiency partly rescues RAD51 loading in cells lacking the BRCA1 tumor suppressor. Taken together these data reveal potential new ATR biomarkers and new genome maintenance factors., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Peptide drugs often accompany epimeric impurities (isomers). Therefore, efficient chemical synthesis of epimers is critical to identify them correctly and investigate their biological activities. Here, we report the rapid synthesis and structure-activity relationship (SAR) studies of eight possible epimers of a somatostatin synthetic analog (SSA), lanreotide (LAN). SPPS and the subsequent on-resin rapid disulfide closure method offered >90% conversion yield for all epimers (P1-P8). Further, we developed an analytical method to separate these epimers, which enabled the profiling of five epimeric impurities in the API, purchased for Somatuline generic formulations. In SAR studies, most LAN epimers revealed compromised antiproliferative activity, while the P7 epimer retained antiproliferative activity similar to LAN API, as supported by in silico SAR studies in detail. Additionally, P7 showed serum stability nearly identical to LAN, suggesting that drug epimers could be a potential API. Current studies will further encourage the development of novel SSA scaffolds., Competing Interests: AB and VG have filed an Indian patent application (IN202211063074) for on-resin disulfide assembly., (This journal is © The Royal Society of Chemistry.)

Background Intracapsular femoral neck fractures account for a majority of hip fractures. This study aimed to investigate the efficacy of valgus osteotomy as a primary treatment for intracapsular femoral neck fractures in adult patients aged 15-60 years, assessing its impact on functional outcomes and fracture union. Methodology A retrospective clinical analysis was conducted at the Department of Orthopedics and Traumatology, Osmania Government General Hospital, Hyderabad, India, focusing on patients treated with primary intertrochanteric valgus osteotomy for intracapsular femoral neck fractures. The study reviewed medical charts and radiographs of six patients aged between 15 and 60 years, diagnosed with recent isolated intracapsular femoral neck fractures, presenting between May 2019 and October 2021. The intervention involved Pauwels' intertrochanteric valgus osteotomy with various fixation methods. Main outcome measures included radiographic union, functional ability assessed by the Harris Hip Score, and evaluation for complications. Results All six patients achieved radiographic union at fracture and osteotomy sites, totaling a 100% success rate. The average follow-up duration was 14.8 months (12-20 months), with an average time of 5.1 months (2.5-6 months) from surgery to radiographic union. One patient experienced union with retroversion, while another developed avascular necrosis (AVN) by the study's conclusion. No instances of hardware failure or non-union were observed. The average Harris Hip Score obtained during the most recent clinical follow-up was 84, ranging from 69 to 94. All six patients regained independent walking ability without any support by the end of the follow-up period. Conclusion The combination of primary Pauwels' intertrochanteric valgus osteotomy with fixed-angle plating proves to be a highly effective method for addressing recent intracapsular femoral neck fractures, resulting in a 100% success rate in achieving union among the patient cohort., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Chakrapani et al.)

Ganirelix, a peptide-based drug used to treat female infertility, has been in high market demand, which attracted generic formulation. A hitherto unknown impurity of ganirelix was observed in our formulation process, which reached ~0.3% in 6 months and led to a detailed investigation of its structure. In-depth analysis of ESI-MS/MS data of this impurity coupled with an artificial intelligence prediction tool led to a highly unusual putative structure, that is, N-(2-carboxyethyl)-ganirelix ( N CE-GA), which was authenticated by chemical synthesis from ganirelix and NMR analysis and via corroborated HPLC and MS/MS data with the formulation-derived impurity., (© 2023 European Peptide Society and John Wiley & Sons Ltd.)

Purpose: Lateralized rhythmic delta activity (LRDA) is highly associated with seizures but generalized rhythmic delta activity (GRDA; symmetric by definition) has no known seizure association. A subset of LRDA includes patterns that are "bilateral asymmetric LRDA" (LRDA-ba), falling between purely unilateral LRDA and GRDA. The significance of this finding has not been previously addressed., Methods: Clinical, EEG, and imaging findings were reviewed in all patients with >6 hours of continuous EEG and LRDA-ba between 2014 and 2019. They were compared with a control group of patients with GRDA, matched 1:1 for prevalence, duration, and frequency of the predominant rhythmic pattern., Results: Two hundred fifty-eight patients with LRDA-ba and 258 matched controls with GRDA were identified. Statistically significant findings included that patients with LRDA-ba were more likely to have presented with an ischemic stroke (LRDA-ba 12.4% vs. GRDA 3.9%) or subdural hemorrhage (8.9% vs. 4.3%); those with GRDA were more likely to have a metabolic encephalopathy (GRDA 10.5% vs. LRDA-ba 3.5%) or "altered mental state" without clear etiology (12.5% vs. 4.3%). Patients with LRDA-ba were significantly more likely to have a background EEG asymmetry (LRDA-ba 62.0% vs. GRDA 25.6%) or focal (arrhythmic) slowing (40.3% vs. 15.5%), and acute (65.5% vs. 46.1%) or focal (49.6% vs. 28.3%) abnormalities on computed tomography scan. Patients with LRDA-ba were more likely to have focal sporadic epileptiform discharges (95.4% vs. 37.9%), lateralized periodic discharges (32.2% vs. 5.0%), and focal electrographic seizures (33.3% vs. 11.2%); however, patients with LRDA-ba alone (i.e., without sporadic epileptiform discharges or PDs) showed only a trend toward increased seizures (17.3%) compared with a matched group of patients with GRDA alone (9.9%, P = 0.08)., Conclusions: Patients with LRDA-ba had a higher proportion of acute focal abnormalities compared with a matched group of patients with GRDA. The LRDA-ba was associated with additional evidence of focal cortical excitability on EEG (sporadic epileptiform discharges and lateralized periodic discharges) and seizures but with only a trend toward increased seizures when other signs of focal excitability were absent., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Objective: To determine whether quantitative EEG analysis of burst suppression can predict seizure recurrence in patients with refractory status epilepticus (RSE) being treated with anesthetic doses of continuous IV antiseizure medications (cIVASM)., Methods: Quantitative assessment of burst suppression (including epileptiform discharges [EDs] and evolution) in 31 occasions (from 27 patients), and correlation with seizure recurrence up to 48 hours post sedative wean., Results: Occasions resulting in seizure recurrence (vs. no seizure recurrence) had lower burst (8.4 vs. 10.6 µV) and interburst interval (IBI) (4.2 vs. 4.8 µV) average amplitude, duration (bursts 2.8 vs. 3.6 s: IBIs 3.6 vs. 4.4 s); and burst total power (0.4 vs. 0.7 µV 2 ). Bursts (0.86 vs. 0.60) and IBIs (0.28 vs. 0.07) with EDs, higher number of EDs within bursts (mean 2.1 vs. 1.4) and IBIs (0.6 vs. 0.2), and positive evolution measures all predicted seizure recurrence, although EDs had the greatest adjusted odds ratio on multivariate analysis., Conclusions: For patients in burst suppression, successful wean of cIVASM was not determined by classical burst suppression measures, but instead how "epileptiform" bursts and IBIs were, as determined by EDs in both bursts and IBIs and surrogates for evolution within bursts., Significance: If confirmed, these objective measures could be used during clinical care to help determine when to wean cIVASM in patients with RSE., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient)., Methods: This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L)., Results: A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19-99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection., Conclusions: Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures., Methods: We conducted a retrospective case series of adults admitted to two academic neurointensive care units between January 2017 and March 2019 who received PGB for treatment of seizures. Data collected included demographics, etiology of brain injury, antiseizure medications, and outcome. Continuous electroencephalogram recordings 48 hours before and after PGB administration were reviewed by electroencephalographers blinded to the administration of antiseizure medications to obtain granular data on electrographic seizure burden. Cyclic seizures were determined quantitatively (i.e., < 50% variation of interseizure intervals for at least 50% of consecutive seizures). Coprimary outcomes were decrease in hourly seizure burden in minutes and decrease in seizure frequency in the 48 hours after PGB initiation. We used nonparametric tests for comparison of seizure frequency and burden and segmented linear regression to assess PGB effect., Results: We included 16 patients; the median age was 69 years, 11 (68.7%) were women, three (18.8%) had undergone a neurosurgical procedure, and five (31%) had underlying epilepsy. All seizures had focal onset; ten patients (62.5%) had cyclic seizures. The median hourly seizure burden over the 48 hours prior to PGB initiation was 1.87 min/hour (interquartile range 1.49-8.53), and the median seizure frequency was 1.96 seizures/hour (interquartile range 1.06-3.41). In the 48 hours following PGB (median daily dose 300 mg, range 75-300 mg), the median number of seizures per hour was reduced by 0.80 seizures/hour (95% confidence interval 0.19-1.40), whereas the median hourly seizure burden decreased by 1.71 min/hour (95% confidence interval 0.38-3.04). When we compared patients with cyclic versus noncyclic seizures, there was a relative decrease in hourly seizure frequency (- 86.7% versus - 2%, p = 0.04) and hourly seizure burden (- 89% versus - 7.8%, p = 0.03) at 48 hours., Conclusions: PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: Essential oils (EOs) like eucalyptus and camphor have pro-convulsant properties. These EOs are present in many over- the- counter balms and oils. The effect of exposure to these EOs and occurrence of seizure is not systematically studied. The aim of this study was to evaluate the relationship between essential oils and the first episode of seizure and breakthrough seizures in known epileptic patients., Methods: This was a multi-center prospective study, conducted in four hospitals over four years. Every person presenting with the first episode of seizure or breakthrough seizure was asked about exposure to EOs, mode of exposure, time to onset of a seizure in relationship to exposure, duration of seizure, type of seizure, and antiepileptic drug therapy., Results: During the four-year period there were 55 patients with essential oil-related seizure (EORS). 22(40 %) had essential oil-induced seizures (EOIS) and 33(60 %) had essential oil-provoked seizures (EOPS). The female: male ratio was 1:1.1, the age of the patients ranged from 8 months to 77 years. In the EOIS group, 95 % had generalized tonic-clonic seizures and 5% had focal impaired awareness seizures. In the EOPS group, 42.4 % had focal impaired awareness seizures, 27.3 % generalized tonic-clonic seizures, 15 % focal to bilateral tonic-clonic seizures, and 15 % focal aware motor seizures. EOs implicated were preparations containing eucalyptus and camphor., Conclusion: Exposure to essential oils of eucalyptus and camphor is an under-recognized cause of the first and breakthrough seizure. Identifying the true causative factor will prevent unnecessary antiepileptic drug therapy and future recurrence., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Essential oils are plant-derived oils and are widely used as an over-the-counter remedy for common ailments. Many essential oils are found to have proconvulsant effects. Here we report a small case series of 3 adults with eseential oil-related status epilepticus., Methods: This was an observational study conducted in a tertiary care hospital in south India from January 2018 to December 2019. We collected the demographic, clinical, and imaging features of all cases of status epilepticus resulting from exposure to essential oils. Cases of status epilepticus secondary to all other causes were excluded., Results: There were 3 young adults with essential oil-related status epilepticus. Two had de novo generalized tonic-clonic status epilepticus, and 1 with posttraumatic occipital lobe epilepsy had focal-impaired awareness status epilepticus. The first 2 cases presented with histories of ingestion of eucalyptus oil. The third case had focal-impaired awareness status epilepticus after topical application of various balms containing eucalyptus and camphor., Conclusions: Proconvulsant essential oils of eucalyptus and camphor can cause both generalized and focal status epilepticus. Physicians dealing with patients of status epilepticus should enquire about the exposure to proconvulsant essential oils., (© 2020 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of the American College of Emergency Physicians.)

Background: The risk of endocarditis varies with CHD complexity and the presence of prosthetic valves. The purpose of the study was therefore to describe incidence and outcomes of prosthetic valve endocarditis in adults with repair tetralogy of Fallot., Methods: Retrospective review of adult tetralogy of Fallot patients who underwent prosthetic valve implantation, 1990-2017. We defined prosthetic valve endocarditis-related complications as prosthetic valve dysfunction, perivalvular extension of infection such abscess/aneurysm/fistula, heart block, pulmonary/systemic embolic events, recurrent endocarditis, and death due to sepsis., Results: A total of 338 patients (age: 37 ± 15 years) received 352 prosthetic valves (pulmonary [n = 308, 88%], tricuspid [n = 13, 4%], mitral [n = 9, 3%], and aortic position [n = 22, 6%]). The annual incidence of prosthetic valve endocarditis was 0.4%. There were 12 prosthetic valve endocarditis-related complications in six patients, and these complications were prosthetic valve dysfunction (n = 4), systemic/pulmonary embolic events (n = 2), heart block (n = 1), aortic root abscess (n = 1), recurrent endocarditis (n = 2), and death due to sepsis (n = 1). Three (50%) patients required surgery at 2 days, 6 weeks, and 23 weeks from the time of prosthetic valve endocarditis diagnosis. Altogether three of the six (50%) patients died, and one of these deaths was due to sepsis., Conclusions: The incidence, complication rate, and outcomes of prosthetic valve endocarditis in tetralogy of Fallot patients underscore some of the risks of having a prosthetic valve. It is important to educate the patients on the need for early presentation if they develop systemic symptoms, have a high index of suspicion for prosthetic valve endocarditis, and adopt a multi-disciplinary care approach in this high-risk population.

Background: Left heart filling pressures, as measured by pulmonary artery wedge pressure (PAWP), is associated with heart failure related mortality. Because of the prognostic importance of PAWP, several echocardiographic indices have been proposed for noninvasive assessment of PAWP. However, these indices have not been validated in the congenital heart disease population. The purpose of this study was to determine the correlation between echocardiographic indices of PAWP, and the effect of high PAWP on transplant-free survival in adults with tetralogy of Fallot (TOF)., Methods: Retrospective study of adult TOF patients that underwent cardiac catheterization at Mayo Clinic, 1990-2017. We selected these pre-defined set of echocardiographic indices of LV diastolic function: mitral valve early velocity (E), mitral valve early and late velocity ratio (E/A), mitral valve deceleration time (DT), mitral annular tissue Doppler early velocity (e'), and left atrial volume index (LAVI)., Results: Of the echocardiographic indices analyzed among 213 patients (age 37 ± 14 years), only E velocity (β = 5.83, standard error = 1.52, p < 0.001) and LAVI (β = 0.14, standard error = 0.05, p = 0.007) correlated with PAWP. LAVI > 28 ml/m 2 had sensitivity of 79% and specificity of 63% (AUC 0.712), and E velocity > 1.0 m/s had sensitivity of 66% and specificity of 89% (AUC 0.692), for detecting PAWP > 15 mmHg. LAVI > 28 ml/m 2 was associated with reduced 10-year transplant-free survival (49% vs 90%, p < 0.001)., Conclusion: This study supports the use of LAVI for noninvasive assessment of PAWP and for prognostication. Further studies are required to validate these results in a different population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 Published by Elsevier B.V.)

Background: Quantitative assessment of right ventricular (RV) systolic function by echocardiography is challenging in patients with congenital heart disease because of the complex geometry of the RV and the iatrogenic structural abnormalities resulting from prior cardiac surgeries. The purpose of this study was to determine the correlation between echocardiographic indices of RV systolic function and cardiac magnetic resonance imaging (CMRI) derived RV ejection fraction (RVEF) in adults with repaired tetralogy of Fallot (TOF)., Methods: Quantitative assessment of RV function was performed with RV tissue Doppler systolic velocity (RV s'), tricuspid annular plane systolic excursion (TAPSE), and fractional area change (FAC). These echocardiographic indices were compared to RVEF from CMRI performed on the same day as echocardiogram., Results: Of 209 patients, the mean RV FAC was 39 ± 9%, TAPSE was 18 ± 4 mm, RV s' was 10 ± 2 cm/s, and RVEF was 40 ± 10%. There was a good correlation between TAPSE and RVEF (r = 0.79, P < .001), good correlation between RV s' and RVEF (r = 0.71, P < .001), and modest correlation between FAC and RVEF (r = 0.66, P < .001). TAPSE < 17 mm effectively discriminated between patients with RV systolic dysfunction defined as RVEF < 47% (sensitivity 81%, specificity 79%, area under the curve [AUC] 0.805). FAC < 40% was associated with RVEF < 47% (sensitivity 72%, specificity 63%, AUC 0.719). RV s' < 11 cm was associated with RVEF < 47% (sensitivity 83%, specificity 68%, AUC 0.798)., Conclusion: Despite the structural and functional abnormalities of the RV in patients with repaired TOF, quantitative assessment of RV systolic function by echocardiography is feasible and had good correlation with CMRI-derived RVEF., (© 2019 Wiley Periodicals, Inc.)

Background: There are limited data about outcomes of coronary artery disease (CAD) in adults with repaired tetralogy of Fallot (TOF). The purpose of this study was to describe the prevalence and treatment of CAD in adults with TOF, and the impact of CAD on long-term survival., Methods: Retrospective review of MACHD database for adults with repaired TOF who underwent aortic root/selective coronary angiogram, 1990-2017. Patients were categorized into three groups: (1) No CAD defined as normal coronary angiogram; (2) Mild CAD defined as ≤50% stenosis in all vessels; and, (3) Significant CAD defined as >50% stenosis in any vessel., Results: We identified 105 (23%) of 465 TOF patients that had angiograms; mean age 47 ± 12 years. The prevalence of mild CAD and significant CAD was 19% (20 patients) and 15% (16 patients), respectively. Of these 16 patient with significant CAD, 9 (56%), 3 (19%), and 4 (24%) patients received guideline directed medical therapy, percutaneous coronary intervention, and coronary artery bypass grafting, respectively. Significant CAD was an independent risk factor for mortality (HR: 2.03, 95% CI 1.64-4.22, P = .022) after adjustment for differences in age, and prevalence of atrial fibrillation and renal dysfunction., Conclusions: Based on a review of a selected cohort of 105 TOF patients, the prevalence of mild CAD and significant CAD was 19% and 15%, respectively. Significant CAD was an independent risk factor for mortality. There is need for more research to determine optimal noninvasive diagnostic strategies and optimal patient selections and methods for revascularization., (© 2019 Wiley Periodicals, Inc.)

Background Available outcomes data for anticoagulation therapy in adults with congenital heart disease ( CHD ) provide assessment of global risk of this therapy for CHD patients (a heterogeneous population), but the risk of complications for the different CHD diagnoses is unknown. The purpose of the study was to describe the indications for anticoagulation, and the incidence and risk factors for major bleeding complication in adults with tetralogy of Fallot. Methods and Results We queried Mayo Adult Congenital Heart Disease (MACHD) database for tetralogy of Fallot patients (aged ≥18 years) that received anticoagulation, 1990-2017. Of 130 patients (42±14 years, 75 men [58%]), warfarin and direct oral anticoagulants were used in 125 (96%) and 5 (4%), respectively because atrial arrhythmias (n=109), mechanical prosthetic valve (n=29), intracardiac thrombus (n=4), pulmonary embolism (n=6), stroke (n=3), and perioperative anticoagulation (n=44). The median hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score for the entire cohort was 1 (0-2) and 27 (21%) had hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2. There were 14 minor bleeding events (1.6% per year) and 11 major bleeding events (1.3% per year) in 8 patients during median follow-up of 74 months (856 patient-years). Mechanical prosthesis (hazard ratio 1.78, CI 1.29-3.77, P=0.021) and hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2 (hazard ratio 1.41, CI 1.03-3.88, P=0.046) were risk factors for major bleeding events. All-cause mortality was higher in patients with major bleeding events (n=6, 75%) compared with patients without major bleeding events (n=25, 21%), P=0.001. Conclusions Considering the heterogeneity of the CHD population, data from the current study may be better suited for clinical decision-making in tetralogy of Fallot patients.

Eucalyptus oil (EO) is an essential oil that is widely used across the globe as an over-the-counter remedy for common ailments. EO-induced seizure (EOIS) has not been recognized as an entity, and physicians rarely ask the history of exposure to eucalyptus oil when seeing a patient with first episode of seizure. Here we report 10 cases of EO inhalation-induced seizures seen over the past 2 years in three tertiary care hospitals. Eight patients had GTCS and two had CPS. We aim to raise awareness of seizures induced by exposure to eucalyptus oil.

The purpose is to evaluate white matter (WM) abnormalities in Wilson's disease (WD) using the technique of diffusion tensor imaging (DTI). The prospective case-control study comprised of 15 drug-naïve patients with WD and 15 controls. The phenotype of subjects was evaluated. The DTI/conventional MRI was acquired (3T MRI): Fractional anisotropy (FA) and mean diffusivity (MD) values were extracted from regions of interest placed in pons, midbrain, bilateral frontal and occipital cerebral white matter, bilateral internal capsules (IC), middle cerebellar peduncles (MCP) and corpus callosum (CC). Six patients showed lobar WM signal changes on T(2)-Weighted (T2W)/Fluid attenuation inversion recovery (FLAIR) images while remaining had normal appearing WM. MD was significantly increased in the lobar WM, bilateral IC and midbrain of WD patients. FA was decreased in the frontal and occipital WM, bilateral IC, midbrain and pons. Normal-appearing white matter on FLAIR images showed significantly increased MD and decreased FA values in both frontal and occipital lobar WM and IC compared with those in controls. Correlation of clinical scores and DTI metrics revealed positive correlation between neurological symptom score (NSS) and MD of anterior limb of right internal capsule, Chu stage and MD of frontal and occipital WM. Negative correlation was observed between the Modified Schwab and England Activities of Daily Living (MSEADL) score and MD of bilateral frontal and occipital WM and IC. This is the probably the first study to reveal widespread alterations in WM by DTI metrics in drug naïve WD. DTI analysis revealed lobar WM abnormalities which is less frequently noted on conventional MRI and suggests widespread WM abnormalities in WD. It may be valuable in assessing the true extent of involvement and therefore the severity of the illness.

Studies on magnetic resonance imaging (MRI) observations in neuronal ceroid lipofuscinosis (NCL) are few and far between. We evaluated the MRI characteristics of patients with NCL and its subtypes. Forty-three out of 68 patients with ultrastructurally confirmed NCL (M:F=46:22; age at evaluation: 6.3±5.2 years) underwent brain MRI evaluation (1998-2010). The demography, phenotype and subtypes of NCL (n=43) [infantile (I-NCL): 5; late infantile (LI-NCL): 26; Juvenile (J-NCL): 11; adult (A-NCL): 1] were recorded. MRI (brain) was carried out using standard sequences in all. Brain atrophy and signal alterations were assessed visually. Brain MRI was abnormal in all 43 patients - diffuse cerebral atrophy (100%), cerebellar atrophy (40%), cerebral leucoencephalopathy (65%) and thalamic T2W-hypointensity (33%). Diffuse cerebral atrophy was noted in: I-NCL (100%), LI-NCL (62%), J-NCL (36%) and A-NCL (100%) [p=0.05]. Cerebellar atrophy was present in: LI-NCL (42%) and J-NCL (55%). Leucoencephalopathy was observed in: I- NCL (100%), LI-NCL (65%), J-NCL (45%) and A-NCL (100%)). Thalamic T2W-hypointensity was most frequent in I-NCL (80%) followed by J-NCL (36%) and LI-NCL (23%). This is the largest study of its kind. The presence of cerebellar/cerebral atrophy, leucoencephalopathy and thalamic T2W-hypointensity in an appropriate clinical setting might provide clues to the diagnosis of NCL: leucoencephalopathy and thalamic hypointensity (T2W) were noted more frequently in I-NCL, periventricular and parieto-occipital hyperintensities in LI-NCL, and cerebellar atrophy in J-NCL.