Comprehensive non-invasive Hemodynamic Assessment in Acute Decompensated Heart Failure-Related Cardiogenic Shock. A step towards echodynamics.

BACKGROUND: Hemodynamic assessment can be determinant in phenotyping cardiogenic shock (CS) and guiding patient management. Aim of this study was to evaluate the correlation between echocardiographic and invasive assessment of hemodynamics in acute decompensated heart failure-related CS (ADHF-CS). METHODS: All consecutive ADHF-CS patients (SCAI shock stage ≥B) undergoing right heart catheterization (RHC) between 2020 and 2022 were prospectively enrolled. Patients underwent echocardiography 30 minutes before RHC. The evaluated hemodynamic parameters and their echocardiographic estimates ("e") comprised cardiac index (CI), wedge pressure (WP), pulmonary artery pressures (PAP), cardiac power output (CPO) and pulmonary artery pulsatility index (PAPi). RESULTS: 101 ADHF-CS patients (56±11 years, 64% SCAI shock stage C, left ventricular ejection fraction 29±5%) were included. Good correlation was found for CI, systolic PAP, RAP and CPO (Pearson r > 0.8 for all), moderate correlation for ePAPi (r=0.67) and PVR (r=0.51), while estimation of WP was weak. The sensitivity and specificity of eCI to identify low output state (CI ≤2.2 l/min/m2) were 0.97 and 0.73 respectively, those of eWP for elevated filling pressures (WP >15 mmHg) were 0.84 and 0.55, those of ePAPs for PAPs ≥35 mmHg were 0.87 and 0.63, those of eCPO for CPO<0.6 W were 0.76 and 0.85, those of ePAPi for PAPi <1.85 were 0.89 and 0.92. Echocardiographic phenotyping of CS showed a good agreement with invasive classification (K value 0.457, p<0.001). CONCLUSIONS: Echocardiographic estimation of hemodynamics and subsequent phenotypization of CS is feasible with good agreement with invasive evaluation.

Postoperative Pulmonary Artery Pulsatility Index Improves Prediction of Right Ventricular Failure After Left Ventricular Assist Device Implantation.

OBJECTIVES: This study evaluated whether the postoperative pulmonary artery pulsatility index (PAPi) is associated with postoperative right ventricular dysfunction after durable left ventricular assist device (LVAD) implantation. DESIGN: Single-center retrospective observational cohort study. SETTING: The University of Kansas Medical Center, a tertiary-care academic medical center. PARTICIPANTS: Sixty-seven adult patients who underwent durable LVAD implantation between 2017 and 2019. INTERVENTIONS: All patients underwent open cardiac surgery with cardiopulmonary bypass under general anesthesia with pulmonary artery catheter insertion. MEASUREMENTS AND MAIN RESULTS: Clinical and hemodynamic data were collected before and after surgery. The Michigan right ventricular failure risk score and the European Registry for Patients with Mechanical Circulatory Support score were calculated for each patient. The primary outcome was right ventricular failure, defined as a composite of right ventricular mechanical circulatory support, inhaled pulmonary vasodilator therapy for 48 hours or greater, or inotrope use for 14 days or greater or at discharge. Thirty percent of this cohort (n = 20) met the primary outcome. Preoperative transpulmonary gradient (odds ratio [OR] 1.15, 95% CI 1.02-1.28), cardiac index (OR 0.83, 95% CI 0.71-0.98), and postoperative PAPi (OR 0.85, 95% CI 0.75-0.97) were the only hemodynamic variables associated with the primary outcome. The addition of postoperative PAPi was associated with improvement in the predictive model performance of the Michigan score (area under the receiver operating characteristic curve 0.73 v 0.56, p = 0.03). An optimal cutoff point for postoperative PAPi of 1.56 was found. CONCLUSIONS: The inclusion of postoperative PAPi offers more robust predictive power for right ventricular failure in patients undergoing durable LVAD implantation, compared with the use of existing risk scores alone.

Unraveling the immunopotentiation of P. aeruginosa PAPI-1 encoded pilin: From immunoinformatics survey to active immunization.

For protection against Pseudomonas aeruginosa strains, a number of vaccine candidates have been introduced thus far. However, despite significant attempts in recent years, there are currently no effective immunogenic Bacteria components against this pathogen on the market. P. aeruginosa encoding a number of different virulence characteristics, as well as the rapid growth in multiple drug-resistant forms, has raised numerous health issues throughout the world. This pathogen expresses three different subtypes of T4P, including IVa, IVb, and Tad which are involved in various cellular processes. Highly virulent strains of P. aeruginosa can encode well-conserved PAPI-1 associated PilS2 pilus. Designing an efficient pili-based immunotherapy approach targeting P. aeruginosa pilus has remained controversial due to the variability heterogeneousness and hidden well-preserved binding site of T4aP and no approved human study is commercially based on IVa pilin. In this investigation, for the first time, through analytical immunoinformatics, we designed an effective chimeric PilS2 immunogen against numerous clinically important P. aeruginosa strains. Through active immunization against the extremely conserved region of the chimeric PilS2 pilin, we showed that PilS2 chimeric pilin whether administered alone or formulated with alum as an adjuvant could substantially stimulate humoral immunological responses in BALB/c mice. Based on these findings, we conclude that PilS2 pilin is therapeutically effective against a variety of highly virulent strains of P. aeruginosa and can act as a new immunogen for more research towards the creation of efficient immunotherapy techniques against the P. aeruginosa as a dexterous pathogen.

The cost and cost efficiency of conducting a 24-h dietary recall using INDDEX24, a mobile dietary assessment platform, compared with pen-and-paper interview in Viet Nam and Burkina Faso.

The INDDEX24 Dietary Assessment Platform (INDDEX24) was developed to facilitate the collection of 24-h dietary recall (24HR) data. Alongside validation studies in Viet Nam and Burkina Faso in 2019-2020, we conducted activity-based costing studies to estimate the cost of conducting a 24HR among women of reproductive age using INDDEX24 compared with the pen-and-paper interview (PAPI) approach. We also modelled alternative scenarios in which: (1) 25-75 % of dietary reference data were borrowed from the INDDEX24 Global Food Matters Database (FMDB); (2) all study personnel were locally based and (3) national-scale surveys. In the primary analysis, in Viet Nam, the 24HR cost US $111 004 ($755/respondent, n 147) using INDDEX24 and $120 483 ($820/respondent, n 147) using PAPI. In Burkina Faso, the 24HR cost $78 105 ($539/respondent, n 145) using INDDEX24 and $79 465 ($544/respondent, n 146) using PAPI. In modelled scenarios, borrowing dietary reference data from the FMDB decreased the cost of INDDEX24 by 17-34 % (Viet Nam) and 5-15 % (Burkina Faso). With all locally based personnel, INDDEX24 cost more than PAPI ($498 v. $448 per respondent in Viet Nam and $456 v. $410 in Burkina Faso). However, at national scales (n 4376, Viet Nam; n 6500, Burkina Faso) using all locally based personnel, INDDEX24 was more cost-efficient ($109 v. $137 per respondent in Viet Nam and $123 v. $148 in Burkina Faso). In two countries and under most circumstances, INDDEX24 was less expensive than PAPI. Higher INDDEX24 survey preparation costs (including purchasing equipment) were more than offset by higher PAPI data entry, cleaning and processing costs. INDDEX24 may facilitate cost-efficient dietary data collection.

Comparing the associations of central venous pressure and pulmonary artery pulsatility index with postoperative renal injury.

Objective: Cardiac surgery-associated acute kidney injury (CS-AKI) is associated with significant morbidity and mortality. We investigated the association of postoperative central venous pressure (CVP) and pulmonary artery pulsatility index (PAPi) with the development of CS-AKI. Methods: This was a single-center, retrospective cohort study of patients undergoing cardiac surgery. CVP and PAPi were acquired hourly postoperatively and averaged for up to 48 h. PAPi was calculated as [(Pulmonary Artery Systolic Pressure-Pulmonary Artery Diastolic Pressure) / CVP]. The primary aim was CS-AKI. Secondary aims were need for renal replacement therapy (RRT), hospital and 30-day mortality, total ventilator and intensive care unit hours, and hospital length of stay. Logistic regression was used to calculate odds of development of renal injury and need for RRT. Results: One thousand two hundred eighty-eight patients were included. The average postoperative CVP was 10.3 mmHg and average postoperative PAPi was 2.01. Patients who developed CS-AKI (n = 384) had lower PAPi (1.79 vs. 2.11, p < 0.01) and higher CVP (11.5 vs. 9.7 mmHg, p < 0.01) than those who did not. Lower PAPi and higher CVP were also associated with each secondary aim. A standardized unit decrease in PAPi was associated with increased odds of CS-AKI (OR 1.39, p < 0.01) while each unit increase in CVP was associated with both increased odds of CS-AKI (OR 1.56, p < 0.01) and postoperative RRT (OR 1.49, p = 0.02). Conclusions: Both lower PAPi and higher CVP values postoperatively were associated with the development of CS-AKI but only higher CVP was associated with postoperative RRT use. When differences in values are standardized, CVP may be more associated with development of CS-AKI when compared to PAPi.

Factors Affecting the Transition from Paper to Digital Data Collection for Mobile Tuberculosis Active Case Finding in Low Internet Access Settings in Pakistan.

Between September 2020 and March 2021, Mercy Corps piloted hybrid digital (CAPI) and paper-based (PAPI) data collection as part of its tuberculosis (TB) active case finding strategy. Data were collected using CAPI and PAPI at 140 TB chest camps in low Internet access areas of Punjab and Khyber Pakhtunkhwa provinces in Pakistan. PAPI data collection was performed primarily during the camp and entered using a tailor-performed CAPI tool after camps. To assess the feasibility of this hybrid approach, quality of digital records were measured against the paper "gold standard", and user acceptance was evaluated through focus group discussions. Completeness of digital data varied by indicator, van screening team, and month of implementation: chest camp attendees and pulmonary TB cases showed the highest CAPI/PAPI completeness ratios (1.01 and 0.96 respectively), and among them, all forms of TB diagnosis and treatment initiation were lowest (0.63 and 0.64 respectively). Vans entering CAPI data with high levels of completeness generally did so for all indicators, and significant differences in mean indicator completeness rates between PAPI and CAPI were observed between vans. User feedback suggested that although the CAPI tool required practice to gain proficiency, the technology was appreciated and will be better perceived once double entry in CAPI and PAPI can transition to CAPI only. CAPI data collection enables data to be entered in a more timely fashion in low-Internet-access settings, which will enable more rapid, evidence-based program steering. The current system in which double data entry is conducted to ensure data quality is an added burden for staff with many activities. Transitioning to a fully digital data collection system for TB case finding in low-Internet-access settings requires substantial investments in M&E support, shifts in data reporting accountability, and technology to link records of patients who pass through separate data collection stages during chest camp events.

Prediction of right ventricular failure after left ventricular assist device implantation: role of vasodilator challenge.

AIMS: Pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation. Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve. METHODS AND RESULTS: Patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients who had undergone RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental, and haemodynamic parameters, at baseline and after nitroprusside infusion and evaluated potential associations with post-LVAD RVF. Of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. Fractional area change (FAC) (OR: 0.647, CI: 0.481-0.871; P = 0.004), pulmonary artery systolic pressure (PASP) (OR: 0.856, CI: 0.761-0.964; P = 0.010), and post-sodium nitroprusside (NTP) PAPi (OR: 0.218, CI: 0.073-0.653; P = 0.006) were independent predictors of post-LVAD RVF. The model combining FAC, PASP, and post-NTP PAPi demonstrated a predictive accuracy of 90.7%. Addition of post-NTP PAPi significantly increased the predictive accuracy of the European Registry for Patients with Mechanical Circulatory Support right-sided heart failure risk score [79.4 vs. 70.4%; area under the curve (AUC): 0.841 vs. 0.724, P = 0.022] and the CRITT score (79.6% vs. 74%; AUC: 0.861 vs. 0.767 P = 0.033). CONCLUSION: Post-NTP PAPi has observed to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi using a vasodilator challenge may represent a method of testing RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed to confirm this hypothesis.

Impact of extracorporeal CPR with transcatheter heart pump support (ECPELLA) on improvement of short-term survival and neurological outcome in patients with refractory cardiac arrest - A single-site retrospective cohort study.

Aim: Extracorporeal cardiopulmonary resuscitation (E-CPR) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a novel lifesaving method for refractory cardiac arrest. Although VA-ECMO preserves end-organ perfusion, it may affect left ventricular (LV) recovery due to increased LV load. An emerging treatment modality, ECPELLA, which combines VA-ECMO and a transcatheter heart pump, Impella, can simultaneously provide circulatory support and LV unloading. In this single-site cohort study, we assessed impact of ECPELLA support on clinical outcomes of refractory cardiac arrest patients. Method: We retrospectively reviewed 165 consecutive cardiac arrest patients, who underwent E-CPR by VA-ECMO with or without intra-aortic balloon pump (IABP) or ECPELLA from January 2012 to September 2021. We assessed 30-day survival rate, neurological outcome, hemodynamic data, and safety profiles including hemolysis, acute kidney injury, blood transfusion and embolic cerebral infarction. Results: Among 165 E-CPR patients, 35 patients were supported by ECPELLA, and 130 patients were supported by conventional VA-ECMO with or without IABP. Following propensity score matching of 30 ECPELLA and 30 VA-ECMO patients, the 30-day survival (ECPELLA: 53%, VA-ECMO: 20%, p < 0.01) and favorable neurological outcome determined by the Cerebral Performance Category score 1 or 2 (ECPELLA: 33%, VA-ECMO: 7%, p < 0.01) were significantly higher with ECPELLA. Patients receiving ECPELLA also showed significantly higher total mechanical circulatory support flow and lower arterial pulse pressure for the first 3 days (p < 0.01) of treatment. There were no statistical differences in safety profiles between treatment groups. Conclusion: ECPELLA may be associated with improved 30-day survival and neurological outcome in patients with refractory cardiac arrest.

Electronic Versus Paper and Pencil Survey Administration Mode Comparison: 2019 Youth Risk Behavior Survey.

BACKGROUND: Since the inception of the Youth Risk Behavior Surveillance System in 1991, all surveys have been conducted in schools, using paper and pencil instruments (PAPI). For the 2019 YRBSS, sites were offered the opportunity to conduct their surveys using electronic data collection. This study aimed to determine whether differences in select metrics existed between students who completed the survey electronically versus using PAPI. METHODS: Thirty risk behaviors were examined in this study. Data completeness, response rates and bivariate comparisons of risk behavior prevalence between administration modes were examined. RESULTS: Twenty-nine of 30 questions examined had more complete responses among students using electronic surveys. Small differences were found for student and school response rates between modes. Twenty-five of 30 adolescent risk behaviors showed no mode effect. CONCLUSIONS: Seven of 44 states and DC participated electronically. Because survey data were more complete; school and student response rates were consistent; and minor differences existed in risk behaviors between modes, the acceptability of collecting data electronically was demonstrated.

Pretransplant Right Ventricular Dysfunction Is Associated With Increased Mortality After Heart Transplantation: A Hard Inheritance to Overcome.

BACKGROUND: Right ventricular dysfunction (RVD) is a major issue in patients with advanced heart failure because it precludes the implantation of left ventricular assist device, usually leaving heart transplantation (HTx) as the only available treatment option. The pulmonary artery pulsatility index (PAPi) is a hemodynamic parameter integrating information of right ventricular function and of pulmonary circulation. Our aim is to evaluate the association of preoperative RVD, hemodynamically defined as a low PAPi, with post-HTx survival. METHODS AND RESULTS: Consecutive adult HTx recipient at 2 Italian transplant centers between 2000 and 2018 with available data on pre-HTx right heart catheterization were included retrospectively. RVD was defined as a value of PAPi lower than the 25th percentile of the study population. The association of RVD with the 1-year post-HTx mortality and other secondary end points were evaluated. Multivariate logistic regression was used to adjust for clinical and hemodynamic variables. Analyses stratified by pulmonary vascular resistance (PVR) status (≥3 Woods units vs <3 Woods units) were also performed. Among 657 HTx recipients (female 31.1%, age 53 ± 11 years), patients with pre-HTx RVD (PAPi of <1.68) had significantly lower 1-year survival rates (77.8% vs 87.1%, P = .005), also after adjusting for estimated glomerular filtration rate, total bilirubin, PVR, serum sodium, inotropes, and mechanical circulatory support at HTx (hazard ratio 2.0, 95% confidence interval, 1.3-3.1). RVD was also associated with post-HTx renal replacement therapy (hazard ratio 2.0, 95% confidence interval 1.05-3.30) and primary graft dysfunction (hazard ratio 1.7, , 95% confidence interval 1.02-3.30). When stratifying patients by estimated PVR status, RVD was associated with worse 1-year survival among patients with normal PVR (76.9% vs 88.3%, P = .003), but not in those with increased PVR (78.6% vs 83.2%, P = .49). CONCLUSIONS: Preoperative RVD, evaluated through PAPi, is associated with mortality and morbidity after HTx, providing incremental prognostic value over traditional clinical and hemodynamic parameters.

Does pulmonary artery pulsatility index predict mortality in pulmonary arterial hypertension?

AIMS: Pulmonary artery pulsatility index (PAPi), defined as [(pulmonary artery systolic pressure - diastolic pulmonary artery pressure)/mean right atrial pressure], is a novel haemodynamic index that predicts right ventricular failure after myocardial infarction and left ventricular assist device implantation. We analysed if a low PAPi is associated with death in our 14 - â€‹year pulmonary arterial hypertension (PAH) registry. METHODS: Consecutive patients with newly diagnosed PAH and complete haemodynamic data were prospectively enrolled into our standing registry between January 2003 and December 2016. PAPi was calculated from baseline invasive right heart catheterization data. A prognostic cut-off value was determined with a decision tree. Baseline characteristics of 'high' and 'low' PAPi groups based on this cut-off were compared, as well as odds of death and time-to-death. RESULTS: One hundred and two patients were included. Mean age was 53 years, and 77% were women. Our multi-ethnic cohort was 64% Chinese, 23% Malay, and 10% Indian. The aetiologies were idiopathic (33%), connective tissue disease (31%), congenital heart disease (24%), and others (12%). The low PAPi group (<5.3) had a greater age (56 years vs. 49 years), lower pulmonary artery systolic pressure (71 mmHg vs. 85 mmHg), and higher mean right atrial pressure (14 mmHg vs. 6 mmHg). Mortality risk was higher in the low PAPi group (adjusted odds ratio: 2.98 and adjusted hazard ratio: 2.23). Mean right atrial pressure was the strongest predictor (hazard ratio 1.114, P = 0.009) when components of PAPi were analysed. CONCLUSIONS: Pulmonary artery pulsatility index was found to be predictive of mortality in PAH and may be a valuable marker for risk stratification. Its prognostic strength may be driven by mean right atrial pressure.

Efficacy of Pulmonary Artery Pulsatility Index as a Measure of Right Ventricular Dysfunction in Stable Phase of Dilated Cardiomyopathy.

BACKGROUND: Right ventricular dysfunction (RVD) in the setting of left ventricular (LV) myocardial damage is a major cause of morbidity and mortality, and the pulmonary artery pulsatility index (PAPi) is a novel hemodynamic index shown to predict RVD in advanced heart failure. However, it is unknown whether PAPi can predict the long-term prognosis of dilated cardiomyopathy (DCM) even in the mild to moderate phase. This study aimed to assess the ability of PAPi to stratify DCM patients without severe symptoms.Methods and Results:Between April 2000 and March 2018, a total of 162 DCM patients with stable symptoms were evaluated, including PAPi, and followed up for a median of 4.91 years. The mean age was 50.9±12.6 years and the mean LV ejection fraction (EF) was 30.5±8.3%. When divided into 2 groups based on median value of PAPi (low, L-PAPi [<3.06] and high, H-PAPi [≥3.06]), even though there were no differences in B-type natriuretic peptide or pulmonary vascular resistance, the probability of cardiac event survival was significantly higher in the L-PAP than in the H-PAP group by Kaplan-Meier analysis (P=0.018). Furthermore, Cox's proportional hazard regression analysis revealed that PAPi was an independent predictor of cardiac events (hazard ratio: 0.782, P=0.010). CONCLUSIONS: Even in patients identified with DCM in the mild to moderate phase, PAPi may help stratify DCM and predict cardiac events.

Impact of tricuspid valve insufficiency on the performance of left ventricular assist devices.

Objective: To evaluate the impact of severe tricuspid valve insufficiency (TVI) at the time of left ventricular assist device (LVAD) implantation on the hemodynamic and LVAD parameters in an acute ovine model. Methods: Stable heart failure (HF) was induced in 10 ovines through the application of 3 ± 1 coronary ligations. Once stable HF was obtained (after 15 ± 5 days), the animals were supported with an LVAD. Hemodynamic data and pump parameters were obtained and compared in 2 settings; first with LVAD in place after weaning from the cardiopulmonary bypass machine (no TVI condition) and second following the induction of severe TVI through resection of the tricuspid valve (TVI condition). Results: There were no statistically significant differences in the hemodynamic and pump parameters between TVI condition and no TVI conditions except for lower cardiac output in the TVI condition (2 [1.38-2.8] L/min vs 3.2 [1.55-3.7] L/min, P = .027) and the expected greater central venous pressure in the TVI condition (26 [24-31] mm Hg vs 15 [13-25] mm Hg, P = .020). A median pump flow of 2.8 (2.45-3.75) L/min versus 2.9 (2.75-3.8) L/min in the TVI condition and no TVI condition was documented (P = .160). Conclusions: Results from this acute animal study suggest that severe TVI in HF with preserved right ventricular function does not have significant impact on the LVAD pump parameters. The observed reduction in cardiac output may warrant further investigations, especially under loading conditions.

Molecular characterization of the pilS2 gene and its association with the frequency of Pseudomonas aeruginosa plasmid pKLC102 and PAPI-1 pathogenicity island.

INTRODUCTION: Pseudomonas aeruginosa is the most common opportunistic pathogen associated with a broad range of infections, including cystic fibrosis, ocular, otitis media, and burn infections. The aim of this study was to show the frequency of the pilS2 gene, and its association with P. aeruginosa plasmid pKLC102 and PAPI-1 pathogenicity island among P. aeruginosa strains. METHODS: The samples were collected from patients with cystic fibrosis, ocular, otitis media, and burn infections between January 2016 and November 2017. DNA was extracted using the DNA extraction kit and was used for PCR assay. PCR with 4 primer-pairs including 976 F/PAPI-1R, 4542 F/intF, SojR/4541 F, and intF/sojR was performed to identify PAPI-1. pKLC102 was detected using three other primer-pairs including cp10F/cp10R, cp44F/cp44R, and cp97F/cp97R. RESULTS: A total of 112 P. aeruginosa isolates were collected from patients with cystic fibrosis (36), burn (20), otitis media (26), and ocular (30) infections. The results of PCR showed that pilS2 gene was identified in 96 (85%) strains. PAPI-1-attB integration was detected among 38 (33.9%) isolates and the circular form of PAPI-1 detected among 17 (14%) isolates. In addition, 79 (70.5%) strains were found to be positive for pKLC102. CONCLUSION: We found that the majority of the isolates may be susceptible to transfer this significant island and the related element pKLC102 into recipient isolates lacking the island owing to high association of the PilS2 pilus with the islands in the studied strains. It is anticipated that strains isolated from burn and eye with the highest rate of PilS2, PAPI-1, and pKLC102 association have a high level of antibiotic resistance.

Haemodynamically Derived Pulmonary Artery Pulsatility Index Predicts Mortality in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary artery (PA) pulsitility index (PAPi) is a novel haemodynamic index shown to predict right ventricular failure in acute inferior myocardial infarction and post left ventricular assist device surgery. We hypothesised that PAPi calculated as [PA systolic pressure - PA diastolic pressure]/right atrial pressure (RAP) would be associated with mortality in the National Institutes of Health Registry for Primary Pulmonary Hypertension (NIH-RPPH). METHODS: The impact of PAPi, the Pulmonary Hypertension Connection (PHC) risk score, right ventricular stroke work, pulmonary artery capacitance (PAC), other haemodynamic indices, and demographic characteristics was evaluated in 272 NIH-RPPH patients using multivariable Cox proportional hazards (CPH) regression and receiver operating characteristic (ROC) analysis. RESULTS: In the 272 patients (median age 37.7+/-15.9years, 63% female), the median PAPi was 5.8 (IQR 3.7-9.2). During 5years of follow-up, 51.8% of the patients died. Survival was markedly lower (32.8% during the first 3years) in PAPi quartile 1 compared with the remaining patients (58.5% over 3years in quartiles 2-4; p<0.0001). The best multivariable CPH survival model included PAPi, the PHC-Risk score, PAC, and body mass index (BMI). In this model, the adjusted hazard ratio for death with increasing PAPi was 0.946 (95% CI 0.905-0.989). The independent ROC areas for 5-year survival based on bivariable logistic regression for PAPi, BMI, PHC Risk, and PAC were 0.63, 0.62, 0.64, and 0.65, respectively (p<0.01). The ROC area for 5-year survival for the multivariable logistic model with all four covariates was 0.77 (p<0.0001). CONCLUSIONS: Pulmonary artery pulsatility index was independently associated with survival in PAH, highlighting the utility of PAPi in combination with other key measures for risk stratification in this population.

Fatores de risco associados ao desenvolvimento de alterações cervicouterinas em mulheres que realizam exame citopatológico / Risk factors associated to the development of changes in the cervix of uterus in women undergoing a cytopathological examination

Introdução: O câncer de colo do útero ainda é um sério problema de saúde pública em nosso país. Aparece em terceiro lugar entre os tipos de câncer mais comum entre as mulheres. Vários são os fatores envolvidos na etiologia desse câncer e suas lesões precursoras. Objetivo: Verificar os principais cofatores associados às alterações cervicouterinas. Casuística e Métodos: Trata-se de um estudo analítico e documental, realizado em um laboratório do município de Surubim-PE, incluindo resultados de exames citopatológicos do período de janeiro de 2014 a dezembro de 2015. Os dados foram avaliados pelo programa PRISM versão 7.0, por meio do teste Qui-quadrado, com intervalo de confiança 95% e razão de prevalência (RP). Resultados: Foram incluídos 1.200 resultados de exames de mulheres na faixa etária entre 14 e 78 anos. Quarenta e três por cento das mulheres pertenciam à faixa etária entre 31 e 47 anos e 86,6% haviam realizado seu último exame citopatológico a menos de três anos. A faixa etária entre 14 e 30 anos esteve associada a um maior risco para o desenvolvimento das anormalidades cervicais (p< 0,001 e OR 2,9). Mulheres que realizaram o exame citopatológico a menos de três anos apresentaram uma maior associação com a presença de lesões intraepiteliais escamosas de baixo grau (LSIL) e atipias escamosas (p < 0,0001 e OR 11,3). A lesão intraepitelial escamosa de baixo grau foi a anormalidade cervical de maior frequência, correspondendo a 46,3%. Mulheres com presença de Gardnerella vaginalis e/ou Mobiluncus spp. apresentaram associação com a presença de anormalidades cervicais (p< 0,0001). Conclusão: Mulheres abaixo de 30 anos, que realizaram exame citopatológico a menos de três anos ou apresentam Gardnerella vaginalis e/ou Mobiluncus spp.devem ser acompanhadas quanto aos possíveis riscos associados ao desenvolvimentode alterações cervicouterinas.

Introduction: Cervical cancer is still a serious public health problem in our country. It appears third among the most common types of cancer among women. Several are the factors involved in the etiology of this cancer and its precursor lesions. Objective: Verify the main cofactors associated with the changes in the cervix of the uterus. Patients and Methods:This is an analytical and documentary study, carried out in a laboratory in the municipality of Surubim-PE, including results of cytopathological exams from January 2014 to December 2015. Data were evaluated using the software PRISM version 7.0, by the Chi-square test, with 95% confidence interval and prevalence ratio (PR). Results: We included 1,200 tests results of women in the age between 14 and 78 years. Forty-three percent of the women were in the age group from 31 to 47 years and 86.6% had performed their last cytopathological examination less than three years. The age group ranging from 14 to 30 years was associated with a higher risk for the development of cervical abnormalities (p< 0.001 and OR 2.9). Women who underwent cytopathological examination less than three years presented a greater association with the presence of low squamous intraepithelial lesions (LSIL) and squamous atypia (p< 0.0001 and OR 11.3). The low-grade squamous intraepithelial lesion was the most frequent cervical abnormality, corresponding to 46.3%. Conclusion: Women under 30 years, who performed cytopathological examination at less than three years or present Gardnerella vaginalis and / or Mobiluncus spp. should be accompanied for the possible risks associated with the development of the changes in the cervix of uterus.

Structural insights into the sequence-specific recognition of Piwi by Drosophila Papi.

The Tudor domain-containing (Tdrd) family proteins play a critical role in transposon silencing in animal gonads by recognizing the symmetrically dimethylated arginine (sDMA) on the (G/A)R motif of the N-terminal of PIWI family proteins via the eTud domains. Papi, also known as "Tdrd2," is involved in Zucchini-mediated PIWI-interacting RNA (piRNA) 3'-end maturation. Intriguingly, a recent study showed that, in papi mutant flies, only Piwi-bound piRNAs increased in length, and not Ago3-bound or Aub-bound piRNAs. However, the molecular and structural basis of the Papi-Piwi complex is still not fully understood, which limits mechanistic understanding of the function of Papi in piRNA biogenesis. In the present study, we determined the crystal structures of Papi-eTud in the apo form and in complex with a peptide containing unmethylated or dimethylated R10 residues. Structural and biochemical analysis showed that the Papi interaction region on the Drosophila Piwi contains an RGRRR motif (R7-R11) distinct from the consensus (G/A)R motif recognized by canonical eTud. Mass spectrometry results indicated that Piwi is the major binding partner of Papi in vivo. The papi mutant flies suffered from both fertility and transposon-silencing defects, supporting the important role conferred to Papi in piRNA 3' processing through direct interaction with Piwi proteins.

Conjugative type IVb pilus recognizes lipopolysaccharide of recipient cells to initiate PAPI-1 pathogenicity island transfer in Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa pathogenicity island 1 (PAPI-1) is one of the largest genomic islands of this important opportunistic human pathogen. Previous studies have shown that PAPI-1 encodes several putative virulence factors, including a major regulator of biofilm formation and antibiotic-resistance traits. PAPI-1 is horizontally transferable into recipient strains lacking this island via conjugation mediated by the specialized type IV pilus. The PAPI-1 encodes a cluster of ten genes associated with the synthesis and assembly of the type IV pilus. The PAPI-1 acquisition mechanism is currently not well understood. RESULTS: In this study, we performed a series of conjugation experiments and identified determinants of PAPI-1 acquisition by analyzing transfer efficiency between the donor and a series of mutant recipient strains. Our data show that common polysaccharide antigen (CPA) lipopolysaccharide (LPS), a homopolymer of D-rhamnose, is required for initiating PAPI-1 transfer, suggesting that this structure acts as a receptor for conjugative type IV pilus in recipient strains. These results were substantiated by experimental evidence from PAPI-1 transfer assay experiments, in which outer membrane or LPS preparations from well-defined LPS mutants were added to the transfer mix to assess the role of P. aeruginosa LPS in PAPI-1 transfer and in vitro binding experiments between pilin fusion protein GST-pilV2' and immobilized LPS molecules were performed. Our data also showed that P. aeruginosa strains that had already acquired a copy of PAPI-1 were unable to import additional copies of the island, and that such strains produced proportionally lower amounts of CPA LPS compared to the strains lacking PAPI-1. CONCLUSIONS: These results suggest that a PAPI-1 exclusion mechanism exists in P. aeruginosa that might serve to regulate the avoidance of uncontrolled expansions of the bacterial genome.