Measures to Prevent Infection in Cardiac Implantable Electronic Device Replacements or Upgrades.

Cardiac implantable electronic device (CIED) infections represent one of the most threatening complications associated with device implantation, due to an increase in morbidity and mortality rates, as well as healthcare costs. Besides, it is important to highlight that when compared to the initial implantation of a device, the risks associated with procedures like generator changes, lead and pocket revisions, or device upgrades double. Consequently, to address this issue, various scoring systems, like the PADIT (Prior Procedures, Age, Depressed Renal Function, Immunocompromised Status, Type of Procedure), the RI-AIAC (Ricerca Sulle Infezioni Associate a ImpiAnto o Sostituzione di CIED), and the Shariff score, along with predictive models, have been developed to identify patients at a greater risk of infection. Moreover, several interventions have been assessed to evaluate their role in infection prevention ranging from improving skin preparation and surgical techniques to considering alternative strategies such as the subcutaneous Implantable Cardioverter-Defibrillator (ICD). Methods like antimicrobial prophylaxis, pocket irrigation, chlorhexidine gluconate pocket lavage, capsulectomy, and the use of antibacterial envelopes have been also explored as preventive measures. In this review, we provide a comprehensive assessment of CIED infections in patients undergoing repeat procedures and the strategies designed to reduce the risk of these infections.

Assisted reality device to guide cardiac implantable device programming in distant rural areas.

BACKGROUND: Patients with cardiac implantable electronic devices (CIEDs) living in rural areas have difficulty obtaining follow-up visits for device interrogation and programming in specialized healthcare facilities. OBJECTIVE: To describe the use of an assisted reality device designed to provide front-line workers with real-time online support from a remotely located specialist (Realwear HTM-1; Realwear) during CIED assistance in distant rural areas. METHODS: This is a prospective study of patients requiring CIED interrogation using the Realwear HMT-1 in a remote rural population in Colombia between April 2021 and June 2022. CIED interrogation and device programming were performed by a general practitioner and guided by a cardiac electrophysiologist. Non-CIED-related medical interventions were allowed and analyzed. The primary objective was to determine the incidence of clinically significant CIED alerts. Secondary objectives were the changes medical interventions used to treat the events found in the device interrogations regarding non-CIED related conditions. RESULTS: A total of 205 CIED interrogations were performed on 139 patients (age 69 ± 14 years; 54% female). Clinically significant CIED alerts were reported in 42% of CIED interrogations, consisting of the detection of significant arrhythmias (35%), lead malfunction (3%), and device in elective replacement interval (3.9%). Oral anticoagulation was initiated in 8% of patients and general medical/cardiac interventions unrelated to the CIED were performed in 52% of CIED encounters. CONCLUSION: Remote assistance using a commercially available assisted reality device has the potential to provide specialized healthcare to patients in difficult-to-reach areas, overcoming current difficulties associated with RM, including the inability to change device programming. Additionally, these interactions provided care beyond CIED-related interventions, thus delivering significant social and clinical impact to remote rural populations.

Pulsed Field Ablation of Atrial Fibrillation: A Comprehensive Review.

Pulsed-field ablation (PFA) has emerged as a promising nonthermal ablation alternative for treating atrial fibrillation (AF). By delivering ultra-rapid high-energy electrical pulses, PFA induces irreversible electroporation, selectively targeting myocardial tissue while sparing adjacent structures from thermal or other damage. This article provides a comprehensive review of multiple pre-clinical studies, clinical studies, and clinical trials evaluating the safety, efficacy, and long-term outcomes of PFA in various settings and patient populations. Overall, the reviewed evidence highlights PFA's potential as a revolutionary ablation strategy for AF treatment. Offering comparable procedural efficacy to conventional ablation methods, PFA distinguishes itself with shorter procedure times and reduced risks of complications such as phrenic nerve palsy and potential esophageal injury. While further research is warranted to establish long-term efficacy, PFA's distinct advantages and evolving clinical evidence suggest a promising future for this novel nonthermal ablation approach. As PFA continues to advance, it has the potential to transform AF ablation procedures, providing a safer alternative for patients with atrial fibrillation.

Association of lung recruitment and change in recruitment-to-inflation ratio from supine to prone position in acute respiratory distress syndrome.

Prone positioning is an evidence-based treatment for patients with moderate-to-severe acute respiratory distress syndrome. Lung recruitment has been proposed as one of the mechanisms by which prone positioning reduces mortality in this group of patients. Recruitment-to-inflation ratio (R/I) is a method to measure potential for lung recruitment induced by a change in positive end-expiratory pressure (PEEP) on the ventilator. The association between R/I and potential for lung recruitment in supine and prone position has not been studied with computed tomography (CT) scan imaging. In this secondary analysis, we sought to investigate the correlation between R/I measured in supine and prone position with CT and the potential for lung recruitment as measured by CT scan. Among 23 patients, the median R/I did not significantly change from supine (1.9 IQR 1.6-2.6) to prone position (1.7 IQR 1.3-2.8) (paired t test p = 0.051) but the individual changes correlated with the different response to PEEP. In supine and in prone position, R/I significantly correlated with the proportion of lung tissue recruitment induced by the change of PEEP. Lung tissue recruitment induced by a change of PEEP from 5 to 15 cmH2O was 16% (IQR 11-24%) in supine and 14.3% (IQR 8.4-22.6%) in prone position, as measured by CT scan analysis (paired t test p = 0.56). In this analysis, PEEP-induced recruitability as measured by R/I correlated with PEEP-induced lung recruitment as measured by CT scan, and could help to readjust PEEP in prone position.

Nucleotides as Bacterial Second Messengers.

In addition to comprising monomers of nucleic acids, nucleotides have signaling functions and act as second messengers in both prokaryotic and eukaryotic cells. The most common example is cyclic AMP (cAMP). Nucleotide signaling is a focus of great interest in bacteria. Cyclic di-AMP (c-di-AMP), cAMP, and cyclic di-GMP (c-di-GMP) participate in biological events such as bacterial growth, biofilm formation, sporulation, cell differentiation, motility, and virulence. Moreover, the cyclic-di-nucleotides (c-di-nucleotides) produced in pathogenic intracellular bacteria can affect eukaryotic host cells to allow for infection. On the other hand, non-cyclic nucleotide molecules pppGpp and ppGpp are alarmones involved in regulating the bacterial response to nutritional stress; they are also considered second messengers. These second messengers can potentially be used as therapeutic agents because of their immunological functions on eukaryotic cells. In this review, the role of c-di-nucleotides and cAMP as second messengers in different bacterial processes is addressed.

The expression of glycosyltransferases sdgA and sdgB in Staphylococcus epidermidis depends on the conditions of biofilm formation.

The Staphylococcus aureus SdrG protein is glycosylated by SdgA and SdgB for protection against its degradation by the neutrophil cathepsin G. So far, there is no information about the role of Staphylococcus epidermidis SdgA or SdgB in biofilm-forming; therefore, the focus of this work was to determine the distribution and expression of the sdrG, sdgA and sdgB genes in S. epidermidis under in vitro and in vivo biofilm conditions. The frequencies of the sdrG, sdgA and sdgB genes were evaluated by PCR in a collection of 75 isolates. Isolates were grown in dynamic (non-biofilm-forming) or static (biofilm-forming) conditions. The expression of sdrG, sdgA and sdgB was determined by RT-qPCR in cells grown under dynamic conditions (CGDC), as well as in planktonic and sessile cells from a biofilm and cells adhered to a catheter implanted in Balb/c mice. The sdrG and sdgB genes were detected in 100% of isolates, while the sdgA gene was detected in 71% of the sample (p < 0.001). CGDC did not express sdrG, sdgA and sdgB mRNAs. Planktonic and sessile cells expressed sdrG and sdgB, and the same was observed in cells adhered to the catheter. In particular, one isolate, capable of inducing a biofilm under treatment with cathepsin G, expressed sdrG and sdgB in planktonic and sessile cells and cells adhering to the catheter. This suggests that bacteria require biofilm conditions as an important factor for the transcription of the sdgA, sdgB and sdrG genes.

Bacteraemia and quick Sepsis Related Organ Failure Assessment (qSOFA) are independent risk factors for long-term mortality in very elderly patients with suspected infection: retrospective cohort study.

BACKGROUND: In older adult patients, bloodstream infections cause significant mortality. However, data on long-term prognosis in very elderly patients are scarce. This study aims to assess 1-year mortality from bacteraemia in very elderly patients. METHODS: Retrospective cohort study in inpatients aged 80 years or older and suspected of having sepsis. Patients with (n = 336) and without (n = 336) confirmed bacteraemia were matched for age, sex, and date of culture, and their characteristics were compared. All-cause mortality and risk of death were assessed using the adjusted hazard ratio (aHR). RESULTS: Compared to controls, cases showed a higher 1-year mortality (34.8% vs. 45.2%) and mortality rate (0.46 vs. 0.69 deaths per person-year). Multivariable analysis showed significant risk of 1-year mortality in patients with bacteraemia (aHR: 1.31, 95% confidence interval [CI] 1.03-1.67), quick Sepsis Related Organ Failure Assessment (qSOFA) score of 2 or more (aHR: 2.71, 95% CI 2.05-3.57), and age of 90 years or older (aHR 1.53, 95% CI 1.17-1.99). CONCLUSIONS: In elderly patients suspected of sepsis, bacteraemia is associated with a poor prognosis and higher long-term mortality. Other factors related to excess mortality were age over 90 years and a qSOFA score of 2 or more.

MES SV40 Cells Are Sensitive to Lipopolysaccharide, Peptidoglycan, and Poly I:C Expressing IL-36 Cytokines.

Mesangial cells (MC) maintain the architecture and cellular communication and indirectly join in the glomerular filtration rate for the correct functioning of the glomerulus. Consequently, these cells are activated constantly in response to changes in the intraglomerular environment due to a metabolic imbalance or infection. IL-36, a member of the IL-1 family, is a cytokine that initiates and maintains inflammation in different tissues in acute and chronic pathologies, including the skin, lungs, and intestines. In the kidney, IL-36 has been described in the development of tubulointerstitial lesions, the production of an inflammatory environment, and is associated with metabolic and mesangioproliferative disorders. The participation of IL-36 in functional dysregulation and the consequent generation of the inflammatory environment by MCs in the presence of microbial stimulation is not yet elucidated. In this work, the MES SV40 cell cultures were stimulated with classical pathogen-associated molecular patterns (PAMPs), mimicking an infection by negative and positive bacteria as well as a viral infection. Lipopolysaccharide (LPS), peptidoglycan (PGN) microbial wall components, and a viral mimic poly I:C were used, and the mRNA and protein expression of the IL-36 members were assessed. We observed a differential and dose-dependent IL-36 mRNA and protein expression under LPS, PGN, and poly I:C stimulation. IL-36ß was only found when the cells were treated with LPS, while IL-36α and IL-36γ were favored by PGN and poly I:C stimulation. We suggest that the microbial components participate in the activation of MCs, leading them to the production of IL-36, in which a specific member may participate in the origin and maintenance of inflammation in the glomerular environment that is associated with infections.

Low Concentration of the Neutrophil Proteases Cathepsin G, Cathepsin B, Proteinase-3 and Metalloproteinase-9 Induce Biofilm Formation in Non-Biofilm-Forming Staphylococcus epidermidis Isolates.

Neutrophils play a crucial role in eliminating bacteria that invade the human body; however, cathepsin G can induce biofilm formation in a non-biofilm-forming Staphylococcus epidermidis 1457 strain, suggesting that neutrophil proteases may be involved in biofilm formation. Cathepsin G, cathepsin B, proteinase-3, and metalloproteinase-9 (MMP-9) from neutrophils were tested on the biofilm induction in commensal (skin isolated) and clinical non-biofilm-forming S. epidermidis isolates. From 81 isolates, 53 (74%) were aap+, icaA−, icaD− genotype, and without the capacity of biofilm formation under conditions of 1% glucose, 4% ethanol or 4% NaCl, but these 53 non-biofilm-forming isolates induced biofilm by the use of different neutrophil proteases. Of these, 62.3% induced biofilm with proteinase-3, 15% with cathepsin G, 10% with cathepsin B and 5% with MMP -9, where most of the protease-induced biofilm isolates were commensal strains (skin). In the biofilm formation kinetics analysis, the addition of phenylmethylsulfonyl fluoride (PMSF; a proteinase-3 inhibitor) showed that proteinase-3 participates in the cell aggregation stage of biofilm formation. A biofilm induced with proteinase-3 and DNAse-treated significantly reduced biofilm formation at an early time (initial adhesion stage of biofilm formation) compared to untreated proteinase-3-induced biofilm (p < 0.05). A catheter inoculated with a commensal (skin) non-biofilm-forming S. epidermidis isolate treated with proteinase-3 and another one without the enzyme were inserted into the back of a mouse. After 7 days of incubation period, the catheters were recovered and the number of grown bacteria was quantified, finding a higher amount of adhered proteinase-3-treated bacteria in the catheter than non-proteinase-3-treated bacteria (p < 0.05). Commensal non-biofilm-forming S. epidermidis in the presence of neutrophil cells significantly induced the biofilm formation when multiplicity of infection (MOI) 1:0.01 (neutrophil:bacteria) was used, but the addition of a cocktail of protease inhibitors impeded biofilm formation. A neutrophil:bacteria assay did not induce neutrophil extracellular traps (NETs). Our results suggest that neutrophils, in the presence of commensal non-biofilm-forming S. epidermidis, do not generate NETs formation. The effect of neutrophils is the production of proteases, and proteinase-3 releases bacterial DNA at the initial adhesion, favoring cell aggregation and subsequently leading to biofilm formation.

[Cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma in cirrhotic patients]. / Colangiocarcinoma y hepatocolangiocarcinoma combinado en pacientes con cirrosis.

BACKGROUND: Cholangiocarcinoma (CCA) is a primary hepatic tumor, frequently found in patients with liver cirrhosis and biliary tract diseases. Its varieties include isolated CCA or "combined hepatocellular-cholangiocarcinoma" (cHCC-CCA). The latter is uncommon, with poorly defined diagnostic criteria and natural history. AIM: To characterize patients with cirrhosis with a pathological diagnosis of CCA and cHCC-CCA. MATERIAL AND METHODS: Forty-nine liver biopsies with a pathological diagnosis of CCA were reviewed. The clinical records of patients were reviewed to fetch demographic variables, etiology of cirrhosis and clinical presentation. RESULTS: Eight of the 49 patients had cirrhosis (16% of CCA biopsies reviewed). Their median age was 64 (27-71) years and five were females. Four patients had CCA, three patients cHCC-CCA and one had a bifocal tumor. Patients in the CCA group were more commonly symptomatic. Alpha-fetoprotein and CA 19-9 levels were elevated in one of eight and four of six patients, respectively. Within 12 months from diagnosis, five of eight patients died. CONCLUSIONS: In most of these cases, the diagnosis of cHCC-CCA and CCA was made in the liver explant study without previous imaging diagnosis. This reinforces the usefulness of the histological study, in specific cases, prior to liver transplantation and emphasizes the importance of systematic explant exploration in these cases.

Current practice in transvenous lead extraction in Latin America: Latin American Heart Rhythm Association survey.

BACKGROUND: Transvenous lead extraction (TLE) is standard of care for the management of patients with cardiac implantable electronic device infection or lead-related complications. Currently, objective data on TLE in Latin America is lacking. OBJECTIVE: To describe the current practice standards in Latin American centers performing TLE. METHODS: An online survey was sent through the mailing list of the Latin American Heart Rhythm Society. Online reminders were sent through the mailing list; duplicate answers were discarded. The survey was available for 1 month, after which no more answers were accepted. RESULTS: A total of 48 answers were received, from 44 different institutions (39.6% from Colombia, 27.1% from Brazil), with most respondents (82%) being electrophysiologists. Twenty-nine institutions (66%) performed <10 lead extractions/year, with 7 (16%) institutions not performing lead extraction. Although most institutions in which lead extraction is performed reported using several tools, mechanical rotating sheaths were cited as the main tool (66%) and only 13% reported the use of laser sheaths. Management of infected leads was performed according to current guidelines. CONCLUSION: This survey is the first attempt to provide information on TLE procedures in Latin America and could provide useful information for future prospective registries. According to our results, the number of centers performing high volume lead extraction in Latin America is smaller than that reported in other continents, with most interventions performed using mechanical tools. Future prospective registries assessing acute and long-term success are needed.

A common bean truncated CRINKLY4 kinase controls gene-for-gene resistance to the fungus Colletotrichum lindemuthianum.

Identifying the molecular basis of resistance to pathogens is critical to promote a chemical-free cropping system. In plants, nucleotide-binding leucine-rich repeat constitute the largest family of disease resistance (R) genes, but this resistance can be rapidly overcome by the pathogen, prompting research into alternative sources of resistance. Anthracnose, caused by the fungus Colletotrichum lindemuthianum, is one of the most important diseases of common bean. This study aimed to identify the molecular basis of Co-x, an anthracnose R gene conferring total resistance to the extremely virulent C. lindemuthianum strain 100. To that end, we sequenced the Co-x 58 kb target region in the resistant JaloEEP558 (Co-x) common bean and identified KTR2/3, an additional gene encoding a truncated and chimeric CRINKLY4 kinase, located within a CRINKLY4 kinase cluster. The presence of KTR2/3 is strictly correlated with resistance to strain 100 in a diversity panel of common beans. Furthermore, KTR2/3 expression is up-regulated 24 hours post-inoculation and its transient expression in a susceptible genotype increases resistance to strain 100. Our results provide evidence that Co-x encodes a truncated and chimeric CRINKLY4 kinase probably resulting from an unequal recombination event that occurred recently in the Andean domesticated gene pool. This atypical R gene may act as a decoy involved in indirect recognition of a fungal effector.

The Extracellular Vesicles from the Commensal Staphylococcus Epidermidis ATCC12228 Strain Regulate Skin Inflammation in the Imiquimod-Induced Psoriasis Murine Model.

Extracellular vesicles (EVs) are evaginations of the cytoplasmic membrane, containing nucleic acids, proteins, lipids, enzymes, and toxins. EVs participate in various bacterial physiological processes. Staphylococcus epidermidis interacts and communicates with the host skin. S. epidermidis' EVs may have an essential role in this communication mechanism, modulating the immunological environment. This work aimed to evaluate if S. epidermidis' EVs can modulate cytokine production by keratinocytes in vitro and in vivo using the imiquimod-induced psoriasis murine model. S. epidermidis' EVs were obtained from a commensal strain (ATC12228EVs) and a clinical isolated strain (983EVs). EVs from both origins induced IL-6 expression in HaCaT keratinocyte cultures; nevertheless, 983EVs promoted a higher expression of the pro-inflammatory cytokines VEGF-A, LL37, IL-8, and IL-17F than ATCC12228EVs. Moreover, in vivo imiquimod-induced psoriatic skin treated with ATCC12228EVs reduced the characteristic psoriatic skin features, such as acanthosis and cellular infiltrate, as well as VEGF-A, IL-6, KC, IL-23, IL-17F, IL-36γ, and IL-36R expression in a more efficient manner than 983EVs; however, in contrast, Foxp3 expression did not significantly change, and IL-36 receptor antagonist (IL-36Ra) was found to be increased. Our findings showed a distinctive immunological profile induction that is dependent on the clinical or commensal EV origin in a mice model of skin-like psoriasis. Characteristically, proteomics analysis showed differences in the EVs protein content, dependent on origin of the isolated EVs. Specifically, in ATCC12228EVs, we found the proteins glutamate dehydrogenase, ornithine carbamoyltransferase, arginine deiminase, carbamate kinase, catalase, superoxide dismutase, phenol-soluble ß1/ß2 modulin, and polyglycerol phosphate α-glucosyltransferase, which could be involved in the reduction of lesions in the murine imiquimod-induced psoriasis skin. Our results show that the commensal ATCC12228EVs have a greater protective/attenuating effect on the murine imiquimod-induced psoriasis by inducing IL-36Ra expression in comparison with EVs from a clinical isolate of S. epidermidis.

Cavotricuspid isthmus line in patients undergoing catheter ablation of atrial fibrillation with or without history of typical atrial flutter: A meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) is the mainstay of catheter ablation (CA) for paroxysmal atrial fibrillation (AF). However, for persistent and long-standing persistent AF, there are no established strategies to improve the success rate of CA. Despite studies indicating that prophylactic cavotricuspid isthmus (CTI) ablation provides no or limited incremental benefit in patients with AF, it is still routinely performed worldwide. OBJECTIVE: We sought to examine whether CTI ablation for AF is associated with improvement in recurrence of all-atrial arrhythmias, compared with PVI alone in patients with and without typical atrial flutter (AFL). METHODS: A systematic review of PubMed, Cochrane, and Embase was performed for clinical studies including AF patients, reporting outcomes of CTI + PVI versus PVI alone. The primary efficacy endpoint was recurrence of all-atrial arrhythmias. RESULTS: Five studies comprising 1400 patients undergoing CTI + PVI versus PVI alone were included; 1110 patients had AF without AFL, and 290 patients had coexistent AF and AFL. After a mean follow-up of 14.4 ± 4.8 months, CTI + PVI was not associated with improvement in recurrence of all-atrial arrhythmias when compared with PVI alone (risk ratio [RR]: 1.29; 95% confidence interval [CI]: 0.93-1.79;p = .13). In the subgroup analysis, there were no differences between both groups in patients with AF without AFL (RR: 1.55; 95% CI: 0.96-2.48; p = .07), and in patients with AF and AFL (RR: 0.91; 95% CI: 0.6-1.39; p = .68). CONCLUSION: In AF patients, irrespective of the presence of typical AFL, additional CTI ablation is not associated with improvement in recurrence of all-atrial arrhythmias, compared with PVI alone.

Overview of Staphylococcus epidermidis cell wall-anchored proteins: potential targets to inhibit biofilm formation.

Currently, the treatment of infections by Staphylococcus epidermidis (S. epidermidis) represents a challenge because some strains have multidrug-resistance to antimicrobial products (antibiotic and biocides) and can produce biofilms. These biofilms protect bacterial cells from both antimicrobials and the host immune response. Therefore, it is crucial to encourage research on the development of new treatments. One method is immunotherapy, targeting components of S. epidermidis, such as S. epidermidis surface (Ses) proteins. Ses is expressed constitutively in most strains, and they participate in biofilm formation. This review is an update on Ses, regarding their structure, biological function, their relationship with S. epidermidis biofilm formation, and its possible role as therapeutic targets to develop immunotherapeutic treatments to prevent infections by S. epidermidis.

Assessment of the tolerance to Fe, Cu and Zn of a sulfidogenic sludge generated from hydrothermal vents sediments as a basis for its application on metals precipitation.

A paramour factor limiting metal-microorganism interaction is the metal ion concentration, and the metal precipitation efficiency driven by microorganisms is sensitive to metal ion concentration. The aim of the work was to determine the tolerance of the sulfidogenic sludge generated from hydrothermal vent sediments at microcosms level to different concentrations of Fe, Cu and Zn and the effect on the microbial community. In this study the chemical oxygen demand (COD) removal, sulfate-reducing activity (SRA) determination, inhibition effect through the determination of IC50, and the characterization of the bacterial community´s diversity were conducted. The IC50 on SRA was 34 and 81 mg/L for Zn and Cu, respectively. The highest sulfide concentration (H2S mg/L) and % of sulfate reduction obtained were: 511.30 ± 0.75 and 35.34 ± 0.51 for 50 mg/L of Fe, 482.48 ± 6.40 and 33.35 ± 0.44 for 10 mg/L of Cu, 442.26 ± 17.1 and 30.57 ± 1.18 for 10 mg/L of Zn, respectively. The COD removal rates were of 71.81 ± 7.6, 53.92 ± 1.07 and 57.68 ± 10.2 mg COD/ L d for Fe (50 mg/L), Cu (40 mg/L) and Zn (20 mg/L), respectively. Proteobacteria, Firmicutes, Chloroflexi and Actinobacteria were common phyla to four microcosms (stabilized sulfidogenic and added with Fe, Cu or Zn). The dsrA genes of Desulfotomaculum acetoxidans, Desulfotomaculum gibsoniae and Desulfovibrio desulfuricans were expressed in the microcosms supporting the SRA results. The consortia could be explored for ex-situ bioremediation purposes in the presence of the metals tested in this work.

Role of IL-36 Cytokines in the Regulation of Angiogenesis Potential of Trophoblast Cells.

IL-36 cytokines (the agonists IL-36α, IL-36ß, IL-36γ, and the antagonist IL-36Ra) are expressed in the mouse uterus and associated with maternal immune response during pregnancy. Here, we characterize the expression of IL-36 members in human primary trophoblast cells (PTC) and trophoblastic cell lines (HTR-8/SVneo and JEG-3) and upon treatment with bacterial and viral components. Effects of recombinant IL-36 on the migration capacity of trophoblastic cells, their ability to interact with endothelial cells and the induction of angiogenic factors and miRNAs (angiomiRNAs) were examined. Constitutive protein expression of IL-36 (α, ß, and γ) and their receptor (IL-36R) was found in all cell types. In PTC, transcripts for all IL-36 subtypes were found, whereas in trophoblastic cell lines only for IL36G and IL36RN. A synthetic analog of double-stranded RNA (poly I:C) and lipopolysaccharide (LPS) induced the expression of IL-36 members in a cell-specific and time-dependent manner. In HTR-8/SVneo cells, IL-36 cytokines increased cell migration and their capacity to interact with endothelial cells. VEGFA and PGF mRNA and protein, as well as the angiomiRNAs miR-146a-3p and miR-141-5p were upregulated as IL-36 response in PTC and HTR-8/SVneo cells. In conclusion, IL-36 cytokines are modulated by microbial components and regulate trophoblast migration and interaction with endothelial cells. Therefore, a fundamental role of these cytokines in the placentation process and in response to infections may be expected.

Oral anticoagulation after catheter ablation of atrial fibrillation and the associated risk of thromboembolic events and intracranial hemorrhage: A systematic review and meta-analysis.

AIMS: We sought to examine whether continuing oral anticoagulation (OAC) after catheter ablation (CA) for atrial fibrillation (AF) is associated with improved outcomes. OAC reduces morbidity and mortality in patients with AF. However, the continuation of OAC following the blanking period of CA is controversial due to conflicting published data. METHODS: A systematic review of Medline, Cochrane, and Embase was performed for studies comparing patients who were continued on OAC (ON-OAC) vs those in which OAC was discontinued (OFF-OAC). CHA2 DS2 VASc score had to be available for the classification of patients into high- or low-risk cohorts (CHA2 DS2 VASc ≥ 2 and ≤ 1, respectively). The primary efficacy outcome was thromboembolic events (TE). Intracranial hemorrhage (ICH) was the primary safety outcome. RESULTS: Five studies comprising 3956 patients were included (mean age, 61.1 ± 2.9 years; 72.4% male, CHA2 DS2 VASc ≤ 1 50.1%; CHA2 DS2 VASc ≥ 2 49.9%). After a mean follow-up of 39.6 ± 11.7 months, OAC-continuation was associated with a significant decrease in risk of TE in the high-risk cohort (CHA2 DS2 VASc ≥ 2) (risk ratio [RR] 0.41, 95% confidence interval [CI] 0.21-0.82, P = .01) with a RR reduction of 59%. ICH was significantly higher in the ON-OAC group (RR, 5.78; 95% CI, 1.33-25.08; P = .02). No significant benefit was observed in the low-risk cohort ON-OAC after the blanking period. CONCLUSION: Continuation of OAC after CA of AF with CHA2 DS2 VASc ≥ 2 is associated with a significant decreased TE risk and a favorable net clinical benefit in spite of ICH being significantly increased in the ON-OAC group. Continued OAC offers no benefit with CHA2 DS2 VASC ≤ 1.

Safety of catheter ablation for atrial fibrillation in the octogenarian population.

INTRODUCTION: Catheter ablation (CA) has been shown to be an effective treatment for atrial fibrillation (AF). The complication rates and outcomes among octogenarians remain poorly studied. We aimed to compare trends, morbidity, and mortality associated with CA for AF among octogenarians versus those less than 80 years old. METHODS: Using weighted sampling from the National Inpatient Sample database, we identified patients with a primary diagnosis of AF and a primary procedure of CA (2004-2013). Our primary outcome was mortality. Secondary outcomes included incidence of major and minor complications. RESULTS: Among 86,119 patients who underwent CA for AF, 3,482 were 80 years old or older. Complications were significantly more frequent in octogenarians; [16.2% (564 of 3,482) versus 9.8% (8,092 of 82,637), P < 0.001]. Of note, there was no significant difference for the composite of major complications; [3.6% (124 of 3482) in octogenarians versus 2.8% (2286 of 82637), P = 0.20]. The total mortality rate was not significant in a multivariate regression analysis (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.35-2.64; P = .94). The presence of chronic renal failure (OR, 4.19; 95% CI, 2.75-6.36; P < 0.001), anemia (OR, 1.75; 95% CI, 1.03-2.97; P = .04), and chronic pulmonary disease (OR, 1.75; 95% CI, 1.11-2.62; P = .015) were predictors of major complications in octogenarians. CONCLUSION: Catheter ablation for AF in octogenarians does not confer a higher mortality risk than in those less than 80 years old. The procedure is associated with a higher rate of overall complications but there was no difference in terms of major complications or death. The presence of anemia, CKD or pulmonary disease were predictors of major complications in octogenarians.

Differential Expression of the apsXRS System by Antimicrobial Peptide LL-37 in Commensal and Clinical Staphylococcus epidermidis Isolates.

The three-component apsXRS system senses and responds to cationic antimicrobial peptides (CAMPs), which induces the expression of the dlt operon and the genes mprF and vrafG, modifying the surface net charge in Staphylococcus epidermidis, resulting in the repulsion of CAMPs. The apsXRS system has been only studied in the S. epidermidis 1457 strain, and there are no studies of prevalence and level of expression of apsXRS in commensal and clinical isolates. From 60 isolates, those selected from commensal healthy skin (n = 20), commensal healthy conjunctive (n = 10), and clinical ocular infection (n = 30) presented the apsX, apsR, and apsS genes in their genomes. Constitutive expression of apsX, apsR, and apsS genes was determined by RT-qPCR in all isolates. It was found that expression of apsX, apsR, and apsS was 3.3-5.9-fold higher in commensal isolates stimulated with LL-37 (15 µg/mL) than in clinical isolates. Similarly, expression of the dlt operon and the genes mprF, and vraFG was 8-10-fold higher in commensal isolates than in clinical. However, LL-37 did not increase the addition of lysine in the phospholipids of the cytoplasmic membrane in any of the isolates. Mutations in the apsS loop region, apsR, and their promoter sequence were not found. These results demonstrated that apsXRS system is essential in all isolates for its constitutive expression; however, LL-37 caused an increase of apsXRS expression in commensal isolates, suggesting that S. epidermidis isolates do not respond in the same way to the presence of LL-37.