Heart failure and atrial fibrillation: Is atrial fibrillation ablation in heart failure pointless or mandatory?

A vast amount of now well-established clinical and epidemiological data indicates a close, interdependent, and symbiotic association between atrial fibrillation (AF) and heart failure (HF). Both AF and HF, when co-exist in a patient, have serious treatment and prognostic implications. Based on the prevailing knowledge of the topic, various societies have issued a number of guidelines regarding the management of patients with AF and HF. Overall, it is the rhythm control strategy that has shown beneficial effect over the rate control strategy with improvement in symptoms of AF and HF. While antiarrhythmic drugs (AADs) and catheter ablation (CA) may be utilized as rhythm control strategy for AF, both AADs and CA have limitations of their own. Furthermore, with the progress made in various pharmacotherapeutic agents in HF, one could question the utility of CA in HF (i.e., whether ablation is mandatory or pointless in patients who have HF). The purpose of this review is to discuss this very point, focusing on the beneficial, neutral, or detrimental outcome of CA based on the category and class of HF.

Are antiarrhythmic agents indicated in premature ventricular complex-induced cardiomyopathy and when?

INTRODUCTION: Premature ventricular complexes (PVCs) are the most common ventricular arrhythmia that are encountered in the clinical practice. Recent data suggests that high PVC burden may lead to the development of PVC-induced cardiomyopathy (PVC-CM) even in patients without structural heart disease. Treatment for effective suppression of PVCs, can reverse PVC-CM. Both antiarrhythmic drugs (AADs) and catheter ablation (CA) are recognized treatment modalities for any cardiac arrhythmias. However, with increasing preference of CA, the role of AADs needs further defining regarding their efficacy, safety, indications and patient selection to treat PVC-CM. METHODS: To ascertain the role of AADs to treat PVC-CM; whether they are indicated to treat PVC-CM, and if so, when, we interrogated PubMed and other search engines for English language publications with key words premature ventricular complexes (PVCs), cardiomyopathy, anti-arrhythmic drugs, catheter ablation, and pharmacological agents. All publications were carefully reviewed and scrutinized by the authors for their inclusion in the review paper. For illustration of cases, ethical standard was observed as per the 1975 Declaration of Helsinki, and the patient was treated as per the prevailing standard of care. Informed consent was obtained from the patient for conducting the ablation procedure. RESULTS: Our literature search specifically the pharmacological treatment of PVC-CM with AADs revealed significant paradigm shift in treatment approach for PVCs and PVC-induced cardiomyopathy. No major large, randomized control trials of AADs versus CA for PVC-CM were found. We found that beta-blockers and calcium channel blockers are particularly effective in the treatment of PVCs originating from right ventricular outflow tract. For Class Ic AADs - flecainide and propafenone, small clinical studies showed Class Ic AADs to be effective in PVC suppression, but their usage was not recommended in patients with significant coronary artery disease. Mexiletine was found to have modest effect on PVC suppression. Studies showed sotalol to significantly reduce PVCs frequency in patients receiving both low and high doses. Studies also showed amiodarone to have higher successful PVC suppression, but not recommended as a first-line treatment for patients with idiopathic PVCs in the absence of symptoms and left ventricular dysfunction. For dronedarone, no major clinical data were available. CONCLUSIONS: Based on the available data in the literature, we conclude that AADs play important role in the treatment of PVC-induced cardiomyopathy. However, appropriate patient selection criteria are vitally important, and in general terms AADs are indicated or polymorphic PVCs, epicardial PVCs; and when CA procedure is contraindicated, or not feasible or failed.

Open-window mapping for ablation of Wolff-Parkinson-White syndrome related hemodynamically unstable tachycardia.

During catheter ablation (CA) of tachycardia, conventional point-by-point mapping may be hindered due to hemodynamic instability. We performed open-window mapping (CARTO, Biosense Webster, USA) in a patient who developed hemodynamic instability during orthodromic atrioventricular reciprocating tachycardia (AVRT) and unwarranted induction of AVRT during attempts to map accessory pathway (AP) with ventricular pacing. With over 11,000 points acquired rapidly, the system accurately identified AP at the mitral valve (MV) annulus where the application of single radiofrequency (RF) lesion promptly eliminated AP's conduction. Our case illustrates the utility of open-window mapping for the ablation of AVRT.

Persistently abnormal device-detected thoracic impedance and OptiVol fluid index related to breast reconstruction surgery.

With significant correlation shown between intrathoracic impedance and intrathoracic fluid volume, the utility of OptiVol fluid index (Medtronic, Minneapolis, MN, USA) in the management of patients with heart failure has been well-described. Although intrathoracic impedance is mainly affected by the changes in the intrathoracic fluid volume, a "false-positive" OptiVol fluid index can occur in the absence of overt congestive heart failure. We present a case of false positive Optivol fluid index elevation in a woman following breast reconstruction surgery.

Network Biology Analyses and Dynamic Modeling of Gene Regulatory Networks under Drought Stress Reveal Major Transcriptional Regulators in Arabidopsis.

Drought is one of the most serious abiotic stressors in the environment, restricting agricultural production by reducing plant growth, development, and productivity. To investigate such a complex and multifaceted stressor and its effects on plants, a systems biology-based approach is necessitated, entailing the generation of co-expression networks, identification of high-priority transcription factors (TFs), dynamic mathematical modeling, and computational simulations. Here, we studied a high-resolution drought transcriptome of Arabidopsis. We identified distinct temporal transcriptional signatures and demonstrated the involvement of specific biological pathways. Generation of a large-scale co-expression network followed by network centrality analyses identified 117 TFs that possess critical properties of hubs, bottlenecks, and high clustering coefficient nodes. Dynamic transcriptional regulatory modeling of integrated TF targets and transcriptome datasets uncovered major transcriptional events during the course of drought stress. Mathematical transcriptional simulations allowed us to ascertain the activation status of major TFs, as well as the transcriptional intensity and amplitude of their target genes. Finally, we validated our predictions by providing experimental evidence of gene expression under drought stress for a set of four TFs and their major target genes using qRT-PCR. Taken together, we provided a systems-level perspective on the dynamic transcriptional regulation during drought stress in Arabidopsis and uncovered numerous novel TFs that could potentially be used in future genetic crop engineering programs.

A Phase 1b Safety Study of SER-287, a Spore-Based Microbiome Therapeutic, for Active Mild to Moderate Ulcerative Colitis.

BACKGROUND & AIMS: Firmicutes bacteria produce metabolites that maintain the intestinal barrier and mucosal immunity. Firmicutes are reduced in the intestinal microbiota of patients with ulcerative colitis (UC). In a phase 1b trial of patients with UC, we evaluated the safety and efficacy of SER-287, an oral formulation of Firmicutes spores, and the effects of vancomycin preconditioning on expansion (engraftment) of SER-287 species in the colon. METHODS: We conducted a double-blind trial of SER-287 in 58 adults with active mild-to-moderate UC (modified Mayo scores 4-10, endoscopic subscores ≥1). Participants received 6 days of preconditioning with oral vancomycin (125 mg, 4 times daily) or placebo followed by 8 weeks of oral SER-287 or placebo. Patients were randomly assigned (2:3:3:3) to groups that received placebo followed by either placebo or SER-287 once weekly, or vancomycin followed by SER-287 once weekly, or SER-287 once daily. Clinical end points included safety and clinical remission (modified Mayo score ≤2; endoscopic subscores 0 or 1). Microbiome end points included SER-287 engraftment (dose species detected in stool after but not before SER-287 administration). Engraftment of SER-287 and changes in microbiome composition and associated metabolites were measured by analyses of stool specimens collected at baseline, after preconditioning, and during and 4 weeks after administration of SER-287 or placebo. RESULTS: Proportions of patients with adverse events did not differ significantly among groups. A higher proportion of patients in the vancomycin/SER-287 daily group (40%) achieved clinical remission at week 8 than patients in the placebo/placebo group (0%), placebo/SER-287 weekly group (13.3%), or vancomycin/SER-287 weekly group (17.7%) (P = .024 for vancomycin/SER-287 daily vs placebo/placebo). By day 7, higher numbers of SER-287 dose species were detected in stool samples from all SER-287 groups compared with the placebo group (P < .05), but this difference was not maintained beyond day 7 in the placebo/SER-287 weekly group. In the vancomycin groups, a greater number of dose species were detected in stool collected on day 10 and all subsequent time points through 4 weeks post dosing compared with the placebo group (P < .05). A higher number of SER-287 dose species were detected in stool samples on days 7 and 10 from subjects who received daily vs weekly SER-287 doses (P < .05). Changes in fecal microbiome composition and metabolites were associated with both vancomycin/SER-287 groups. CONCLUSIONS: In this small phase 1b trial of limited duration, the safety and tolerability of SER-287 were similar to placebo. SER-287 after vancomycin was significantly more effective than placebo for induction of remission in patients with active mild to moderate UC. Engraftment of dose species was facilitated by vancomycin preconditioning and daily dosing of SER-287. ClinicalTrials.gov ID NCT02618187.

Redirecting host preexisting influenza A virus immunity for cancer immunotherapy.

We tested the concept that host preexisting influenza A virus immunity can be redirected to inhibit tumor growth and metastasis through systemic administration of influenza A virus-related peptides to targeted tumors. Mice infected with influenza A virus strain A/Puerto Rico/8/34 (PR8) were used as a model of a host with preexisting viral immunity. The extent to which preexisting influenza A immunity in PR8-immunized mice can be redirected to inhibit tumor growth and metastasis was first examined by ectopic expression of influenza A nucleoprotein (NP) and hemagglutinin (HA) in syngeneic mammary tumor cells via lentiviral transduction. Then, the feasibility of implementing this strategy using a systemic therapy approach was assessed by systemic delivery of major histocompatibility complex class I (MHC-I)-compatible peptides to targeted mammary tumors overexpressing human epidermal growth factor receptor-2 (HER2) in mice using a novel HER2-targeting single-lipid nanoparticle (SLNP). Our results show that preexisting influenza A immunity in PR8-immunized mice could be quickly redirected to syngeneic tumors expressing influenza A NP and HA, leading to strong inhibition of tumor growth and metastasis and improvement of survival compared to the findings in antigen-naïve control mice. MHC-I-compatible peptides could be delivered to targeted mammary tumors in mice using the HER2-targeting SLNP for antigen presentation, which subsequently redirected preexisting influenza A immunity to the tumors to exert antitumor activities. In conclusion, preexisting influenza A immunity can be repurposed for cancer immunotherapy through systemic delivery of influenza A-related peptides to targeted tumors. Further development of the strategy for clinical translation is warranted.

Enhanced electrical conductivity of anticorrosive coatings by functionalized carbon nanotubes: effect of hydrogen bonding.

Carbon nanotubes and nanofibers (CNFs) are well-known nano additives to produce coating materials with high electrical and thermal conductivity and corrosion resistance. In this paper, coating materials incorporating hydrogen bonding offered significantly lower electrical resistance. The hydrogen bonding formed between functionalized carbon nanotubes and ethanol helped create a well-dispersed carbon nanotube network as the electron pathways. Electrical resistivity as low as 6.8 Ω cm has been achieved by adding 4.5 wt% functionalized multiwalled carbon nanotubes (MWNT-OH) to 75%polyurethane/25%ethanol. Moreover, the thermal conductivity of polyurethane was improved by 332% with 10 wt% addition of CNF. Electrochemical methods were used to evaluate the anti-corrosion properties of the fabricated coating materials. 75%polyurethane/25%ethanol with the addition of 3.0 wt% of MWNT-OH showed an excellent corrosion rate of 5.105 × 10-3mm year-1, with a protection efficiency of 99.5% against corrosive environments. The adhesion properties of the coating materials were measured following ASTM standard test methods. 75%polyurethane/25%ethanol with 3.0 wt% of MWNT-OH belonged to class 5 (ASTM D3359), indicating the outstanding adhesion of the coating to the substrate. These nanocoatings with enhanced electrical, thermal, and anti-corrosion properties consist of a choice of traditional coating materials, such as polyurethane, yielding coating durability with the ability to tailor the electrical and thermal properties to fit the desired application.

Implications of "slower" ventricular tachycardia on clinical management and detection and therapy function of implantable cardioverter defibrillators.

Sophisticated dual-chamber atrioventricular and rate-responsive pacing therapies, cardiac resynchronization therapy (CRT), detection and therapies for ventricular tachycardia and fibrillation (VT/VF) form some major components of multitask functions of current implantable cardioverter defibrillators (ICDs). Appropriate programming of these devices is necessary for them to perform all such tasks precisely. In this report, we describe a case of a patient with Chagas cardiomyopathy with marked cardiomegaly, scarred ventricles, prior epicardial and endocardial ablations and on antiarrhythmic pharmacotherapy for VT, who presented with symptomatic wide complex tachycardia at a slower rate than definition of VT, and in whom programming for detection and therapy for "slow" VT could not be performed due to default technological limitation of the CRT-D.

One year outcomes of atrial fibrillation ablation: Contemporary analysis of the United States Nationwide Readmission Database.

BACKGROUND: Data on long-term outcomes of catheter ablation (CA) for atrial fibrillation (AF) in outside of clinical trials settings are sparse. OBJECTIVE: We aimed to assess outcomes and readmissions at 1 year following admission for CA for AF. METHODS: Utilizing the Nationwide Readmissions Database (2016-2018), we identified patients with CA among all patients with a primary admission diagnosis of AF, and a control group by propensity score match adjusted for age, sex, comorbidities, CHA2DS2-VASc scores, and the hospital characteristics. The primary outcome was a composite of unplanned heart failure (HF), AF and stroke-related readmissions, and death at 1 year, and secondary outcomes were hospital outcomes and all-cause readmission rates. RESULTS: The study cohort consisted of 29,771 patients undergoing CA and 63,988 controls. Patients undergoing CA were younger with lower CHA2DS2-VASc scores and less comorbidities. Over a follow-up of 170 ±1.1 days, the primary outcome occurred in 5.2% in CA group and 6.0% of controls (hazard ratio [HR] and 95% confidence interval [CI]: 0.86 [0.76-0.94], p = .002). CA affected AF and stroke related readmission, but showed no effect on HF and mortality outcome. Male sex (HR: 0.83 [0.74-0.94], p = .03), younger age (HR: 0.71 [0.61-0.83], p < .001], and lower CHA2DS2-VASc scores (HR: 0.68 [0.55-0.84], p < .001) were associated with lower risk of primary outcome with CA. CONCLUSION: In this study, CA for AF was associated with significantly lower AF and stroke-related admissions, but not to HF or all-cause readmission. Better outcomes were seen among males, younger patients, and in patients with less comorbidities and low CHA2DS2-VASc scores.

Acute Pulmonary Embolism in an Intensive Care Unit Setting in Sierra Leone.

INTRODUCTION: In Sierra Leone, the lack of information on pulmonary embolism (PE) limits the access to evidence-based standard of diagnostic work-up and management of the disease. The objective of this study was to describe the clinical characteristics and management of acute pulmonary embolism in our setting and to determine whether the pre-test probability scoring algorithms were used prior to Computed Tomography Pulmonary Angiogram (CTPA) request. METHODS: This retrospective observational study was conducted on CTPA-confirmed PE patients admitted to the Intensive Care Unit, Choithrams Memorial Hospital, in Freetown, Sierra Leone between July 2014 to June 2019. Clinical data, and pertinent investigations related to PE were determined. CTPA findings were correlated with the patient's hemodynamic status. The calculated pretest clinical probability scores (PCPS) for each patient were compared to the CTPA results. RESULTS: CTPA-confirmed PE in the study cohort was 79, with a rate of 16 new PE per year. The frequency of PE was 1.9% of the total hospital admission per year. The mean age was 64.1 ± 17.9 years, median age was 63.3years (range: 23-89 years), with 55.7% of the cohort being females. Dyspnea (78.5%) and tachycardia (69.6%) were the commonest signs and symptoms documented, with immobilization (34.2%) being the prevalent risk factor, while hypertension (48.1%) was the most common co-morbidity. The PCPS algorithm was underutilized, as "Wells Score" was documented in only 9.5% while "modified Geneva score" was never used by hospital physicians. PE with hemodynamic stability was significantly more common than PE with unstable hemodynamic status [55 (69.6%) vs 24 (30.4%), p=0.015]. All patients were managed only with anticoagulants. The overall in-hospital mortality was 17.7%. CONCLUSION: Since PCPS was hardly calculated by doctors in the diagnosis of PE, the study showed that the diagnostic algorithm for suspected PE was infrequently used in clinical practice. The use of empirical judgement by doctors in requesting for CTPA may have accounted for low rate in the diagnosis of PE per year. The establishment of P.E registry in Sierra Leone is imperative.

INTRODUCTION: En Sierra Leone, le manque d'informations sur l'embolie pulmonaire (EP) limite l'accès à des normes de diagnostic et de prise en charge de la maladie fondées sur des preuves. L'objectif de cette étude était de décrire les caractéristiques cliniques et la prise en charge de l'embolie pulmonaire aiguë dans notre établissement et de déterminer si les algorithmes de notation de la probabilité pré-test étaient utilisés avant la demande d'angiographie pulmonaire par tomodensitométrie (CTPA). MÉTHODES: Cette étude observationnelle rétrospective a été menée sur des patients atteints d'EP confirmée par CTPA admis à l'unité de soins intensifs, Choithrams Memorial Hospital, à Freetown, Sierra Leone, entre juillet 2014 et juin 2019. Les données cliniques, et les investigations pertinentes liées à l'EP ont été déterminées. Les résultats du CTPA ont été corrélés avec l'état hémodynamique du patient. Les scores de probabilité clinique prétest (PCPS) calculés pour chaque patient ont été comparés aux résultats du CTPA. RÉSULTATS: Le nombre d'EP confirmées par CTPA dans la cohorte étudiée était de 79, avec un taux de 16 nouvelles EP par an. La fréquence de l'EP était de 1,9 % du nombre total d'hospitalisations par an. L'âge moyen était de 64,1 ± 17,9 ans, l'âge médian de 63,3 ans (fourchette : 23-89 ans), 55,7 % de la cohorte étant des femmes. La dyspnée (78,5 %) et la tachycardie (69,6 %) étaient les signes et symptômes les plus fréquemment documentés, l'immobilisation (34,2%) étant le facteur de risque prévalent, tandis que l'hypertension (48,1 %) était la comorbidité la plus courante. L'algorithme PCPS était sous-utilisé, le " score de Wells " n'étant documenté que dans 9,5 % des cas, tandis que le " score de Genève modifié " n'était jamais utilisé par les médecins hospitaliers. L'EP avec stabilité hémodynamique était significativement plus fréquente que l'EP avec état hémodynamique instable [55 (69,6 %) vs 24 (30,4 %), p=0,015]. Tous les patients ont été traités uniquement par anticoagulants. La mortalité globale à l'hôpital était de 17,7 %. CONCLUSION: Étant donné que le PCPS était rarement calculé par les médecins pour le diagnostic de l'EP, l'étude a montré que l'algorithme diagnostique pour l'EP suspectée était rarement utilisé dans la pratique clinique. L'utilisation d'un jugement empirique par les médecins pour demander un CTPA peut expliquer le faible taux de diagnostic de l'EP par an. L'établissement d'un registre de l'E.P. en Sierra Leone est impératif. Mots-clés: Embolie pulmonaire, caractéristiques cliniques, gestion, Sierra Leone.

Implantable cardioverter defibrillator shocks from ventricular tachyarrhythmias in patients with ischemic heart disease: Preventative measures, shortcomings, cost-effectiveness, and global practice perspectives.

Implantable cardioverter defibrillators (ICDs) have proven to be life-saving devices in patients with ischemic cardiomyopathy (ICM) who are prone to develop ventricular tachycardia (VT) and fibrillation (VF). Antiarrhythmic drugs (AADs) are commonly prescribed in many such patients with ICDs to treat and prevent different forms of arrhythmias in clinical practice. When these patients experience recurrent monomorphic VT despite chronic AADs therapy, or when AAD therapy is contraindicated or not tolerated, and VT storm is refractory to AAD therapy, catheter ablation constitute guideline-based class I indication of treatment. However, what should be the most appropriate strategy to prevent first ICD shock or subsequent multiple shocks from VT/VF in patients with ICM who undergo ICD implantation without prior incidence of cardiac arrest, remains debatable. The purpose of this review is to discuss preventative aspects of ICD shocks for VT and the shortcomings of these measures along with the cost-effectiveness and global perspectives based on the current knowledge of the topic.

Alterations in atrial electrogram amplitude as steady sinus rhythm transitions to paroxysmal atrial fibrillation during continuous monitoring in patients with implantable cardiac devices: Insights from the IMPACT study.

OBJECTIVES: We aimed to evaluate whether device measured amplitudes of atrial electrogram (AEGM) would change when measured in sinus rhythm (SR) transitioning to paroxysmal atrial fibrillation (AF) from previous steady SR, and significance of such change. METHODS: From the IMPACT trial's database we selected two groups; (A) those who developed AF (n = 164), and (B) propensity-matched control (n = 459) who stayed in SR during continuous Home Monitoring (HM) to compare AEGMs amplitudes at baseline SR and transition phase. RESULTS: During 420.0 ± 349.2 days (mean ± SD) from first postenrollment HM transmission to AF event transmission in Group A, and corresponding 515.3 ± 407.0 days in Group B, baseline and transition AEGM amplitude were 2.88 ± 1.146 and 2.74 ± 1.186 mV, respectively, for Group A (p = .1), and 2.88 ± 1.155 and 2.79 ± 1.145, respectively, for Group B (p < .005). Comparison of differences of AEGM amplitude, 0.14 ± 1.072 mV in Group A and 0.09 ± 0.893 mV in Group B were insignificant (p = .3). Age, sex, and hypertension identified as confounders had no association to AEGM changes (p = NS). CONCLUSIONS: Independent of age, sex, and hypertension, AEGMs amplitudes decline over a long period of time in patients with defibrillators and substrate for AF. The significance of such change remains unclear as it occurs whether patients develop AF or not, but raises a possibility of progressive atrial myopathy that patients with substrate for AF may be predisposed to.

Safety and complications of catheter ablation for atrial fibrillation: Predictors of complications from an updated analysis the National Inpatient Database.

BACKGROUND: Catheter ablation is increasingly employed in the management of atrial fibrillation (AF). Data regarding safety of ablation of AF is largely derived from controlled clinical trials. OBJECTIVES: The aim of this study was to analyze safety and complications of AF ablation performed in a "real world" setting outside of clinical trials, and obtain insights on predictors of complications. METHODS: We utilized the National Inpatient Sample database, to identify all patients who underwent AF ablations between 2015 and 2017 using International Classification of Disease-Tenth revision codes. Complications were defined as per the Agency for Health Care Research and Quality Guidelines. Statistical tests including multivariate logistic regression were performed to determine predictors of complications. RESULTS: Among 14,875 cases of AF ablation between 2015 and 2017, a total of 1884 complications were identified among 1080 (7.2%) patients. Patients with complications were likely to be older and female with a higher burden of comorbidities. A 27% increase in complications was observed from 2015 to 2017, driven by an increase in pericardial complications. Multivariate regression analysis revealed that pulmonary hypertension (adjusted odds ratio [aOR]: 1.99, p = .041) and chronic kidney disease (CKD; aOR: 1.67, p = .024), were independent predictors of complications. Centers with higher procedural volumes were associated with lower complication rates. CONCLUSIONS: Complication rates related to AF ablations remain substantially high. Presence of pulmonary hypertension and CKD are predictive of higher procedural complications. Furthermore, hospital procedure volume is an important factor that correlates with complication rates.

Clinical presentations and outcomes in pulmonary embolism patients with cancer.

To study whether a diagnosis of cancer affects the clinical presentation and outcomes of patients with pulmonary embolism (PE). A retrospective analysis was performed of all consecutive patients diagnosed with PE on a computed tomography scan from 2014 to 2016 at an urban tertiary-referral medical center. Baseline characteristics, treatment decisions, and mortality data were compared between study subjects with and without a known diagnosis of active cancer. There were 581 subjects, of which 187 (33.0%) had a diagnosis of cancer. On average, cancer subjects tended to be older (64.8 vs. 58.5 years, p < 0.01), had lower body mass index (BMI) (29.0 vs. 31.5 kg/m2, p = 0.01), and were less likely to be active smokers (9.2% vs. 21.1%, p < 0.01), as compared to non-cancer subjects. Cancer subjects were also less likely to present with chest pain (18.2% vs. 37.4%, p < 0.01), syncope (2.7% vs. 6.6%, p = 0.05), bilateral PEs (50% vs. 60%, p = 0.025), and evidence of right heart strain (48% vs. 58%, p = 0.024). There was no difference in-hospital length of stay (8.9 vs. 9.4 days, p = 0.61) or rate of intensive care unit (ICU) admission (31.9% vs. 33.3%, p = 0.75) between the two groups. Presence of cancer increased the risk of all-cause one-year mortality (adjusted HR 9.7, 95% CI 4.8-19.7, p < 0.01); however, it did not independently affect in-hospital mortality (adjusted HR 2.9, 95% CI 0.86-9.87, p = 0.086). Patients with malignancy generally presented with less severe PE. In addition, malignancy did not independently increase the risk of in-hospital mortality among PE patients.

Utilization of extracorporeal life support for diffuse alveolar damage and diffuse alveolar hemorrhage: A systematic review.

Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty-two articles consisting of 38 patients were selected, and patient-level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti-nuclear antibody (ANA) in 6/38 (15.8%), and anti-glomerular basement membrane (anti-GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno-venous type (VV-ECMO) in 28/38 (73.7%), veno-arterial type (VA-ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD-ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P = .46) or VA- versus VV-ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre- versus post-ECLS comparison of blood gases showed improvement in median PaO2 (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P < .001), PaO2:FiO2 ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P < .01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P = .086). Overall, 94.7% (36/38) of patients survived to decannulation while 30-day mortality was 10.5% (4/38) with no differences between VA- and VV-ECMO (P = 1 and P = .94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short-term survival.

Human beta defensins may be a multifactorial modulator in the management of diabetic wound.

Diabetic wound (DW) is considered as one of the serious complications associated with diabetes mellitus. Though some pharmacological approaches are available for managing DW, none of them has been reported to be very effective. Widely accepted options for its management include treatment of infection caused by various pathogens, wound debridement, reducing the period of the prolonged inflammatory phase, and supervision of the remodeling phase of wound healing. Satisfactory management of DW thus requires exploring new avenues for finding a potential therapeutic strategy. Literature shows that human beta defensins (HBDs) help in combating the insulin resistance by inhibiting the production of glucocorticoids, reducing chronic inflammation by acting through Toll-like receptor signaling pathway, and provoking cell migration, proliferation, angiogenesis, and stabilization of fibroblasts and keratinocytes, ultimately resulting in wound closure. In the present review, beneficial role of HBDs in the treatment of DW is discussed in detail.

The predictive value of the Pleth Variability Index on fluid responsiveness in spontaneously breathing anaesthetized children-A prospective observational study.

BACKGROUND: In children, the preoperative hydration status is an important part of the overall clinical assessment. The assumed preoperative fluid deficit is often routinely replaced during induction without knowing the child's actual fluid status. AIM: We investigated the predictive value of the Pleth Variability Index as a measure of fluid responsiveness in spontaneously breathing anesthetized children. METHODS: Pleth Variability Index, stroke volume and Cardiac Index, measured by electrovelocimetry, mean blood pressure, and heart rate were recorded during anesthesia induction in 50 pediatric patients <6 years. Baseline values were compared to values recorded after administration of 10 mL/kg of Ringer's lactate and during two passive leg raising tests (before and after fluid administration). Fluid responsiveness was defined as an increase of ≥10% in stroke volume. RESULTS: Only in fluid responsive patients, Pleth Variability Index values were higher before fluid administration than thereafter (21.4 ± 5.9% vs 15.0 ± 9.4%, 95% CI of difference 1.1 to 11.8%, P = .02). Pleth Variability Index values at baseline were higher in fluid responders (21.4 ± 5.9%) than in fluid nonresponders (15.3 ± 7.7%), 95% CI of difference 1.6 to 10.6%, P = .009. The area under the receiver operating curve indicating fluid responsiveness was 0.781 (95% CI 0.623 to 0.896, P = .0002), with the highest sensitivity (82%) and specificity (70%) at a Pleth Variability Index of >15% (Positive predictive value 2.71 (95% CI: 1.4 to 5.2)). Only in fluid responders, the Pleth Variability Index decreased during passive leg raising, while stroke volume increased. CONCLUSIONS: The Pleth Variability Index may be of additional value to predict fluid responsiveness in spontaneously breathing anesthetized children. A significant overlap in baseline Pleth Variability Index values between fluid responsive and nonfluid responsive patients does not allow a reliable recommendation as to a cut off value.

Scn2a deletion improves survival and brain-heart dynamics in the Kcna1-null mouse model of sudden unexpected death in epilepsy (SUDEP).

People with epilepsy have greatly increased probability of premature mortality due to sudden unexpected death in epilepsy (SUDEP). Identifying which patients are most at risk of SUDEP is hindered by a complex genetic etiology, incomplete understanding of the underlying pathophysiology and lack of prognostic biomarkers. Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, while searching for biomarkers of SUDEP risk embedded in electroencephalography (EEG) and electrocardiography (ECG) recordings. The human epilepsy gene Kcna1 encodes voltage-gated Kv1.1 potassium channels that act to dampen neuronal excitability whereas Scn2a encodes voltage-gated Nav1.2 sodium channels important for action potential initiation and conduction. SUDEP-prone Kcna1-/- mice with partial genetic ablation of Nav1.2 channels (i.e. Scn2a+/-; Kcna1-/-) exhibited a two-fold increase in survival. Classical analysis of EEG and ECG recordings separately showed significantly decreased seizure durations in Scn2a+/-; Kcna1-/- mice compared with Kcna1-/- mice, without substantial modification of cardiac abnormalities. Novel analysis of the EEG and ECG together revealed a significant reduction in EEG-ECG association in Kcna1-/- mice compared with wild types, which was partially restored in Scn2a+/-; Kcna1-/- mice. The degree of EEG-ECG association was also proportional to the survival rate of mice across genotypes. These results show that Scn2a gene deletion acts as protective genetic modifier of SUDEP and suggest measures of brain-heart association as potential indices of SUDEP susceptibility.