Resultados de un programa de cuidados paliativos en pacientes con insuficiencia cardiaca avanzada en etapa final de vida / Results of a palliative care program in patients with advanced heart failure in the end-of-life stage

Introducción: La prevalencia de la insuficiencia cardiaca se encuentra en aumento, manifestándose en la fase avanzada (ICA) con síntomas invalidantes. Las exacerbaciones, las internaciones frecuentes y la elevada morbimortalidad son condiciones para ser asistidas por cuidados paliativos. Se diseñó un programa de cuidados paliativos cardiológicos (CPC) para monitorear síntomas, profundizar la comunicación, determinar directivas anticipadas y adecuar el esfuerzo terapéutico. El objetivo del estudio fue comparar la asistencia de pacientes fallecidos por ICA, antes y después de un programa de CPC. Material y métodos: Estudio observacional y comparativo. Se ofreció CPC a pacientes con ICA y se comparó con grupo control que no ingresó al programa por falta de disponibilidad (preCPC). En el análisis estadístico se evaluaron las variables categóricas mediante pruebas no paramétricas y las continuas comparadas mediante la prueba de U de Mann-Whithey. Resultados: Ingresaron 77 pacientes en preCPC y 65 al programa CPC. Tenían características poblacionales similares: edad (mediana) 75 años, género masculino: 70 %. Se registró una disminución de la duración (27,3 vs. 7,2 días; p < 0,001) y del número de internaciones (2,64 vs. 1,51; p < 0,001) a favor del grupo CPC. Las intervenciones invasivas los últimos 5 días de vida predominan en preCPC: asistencia ventilatoria mecánica (52,7 vs. 7,8 %; p < 0,001), hemodiálisis (41 vs. 5,5 %; p < 0,001), reanimación cardiopulmonar (88,2 vs. 11 %; p < 0,001), acceso vascular central (75,7 vs. 26,5 %, p < 0,01) y uso de inotrópicos (70,5 vs. 20 %; p < 0,001). Las intervenciones no invasivas o de confort predominaron en CPC: sedación paliativa (3 vs. 25 %), uso de opioides (35 vs. 58,3 %), desconexión de cardiodesfibrilador (0 vs. 37,5 %) y directrices de no reanimación cardiopulmonar (3 vs. 77 %; p < 0,001). La mortalidad en sectores de cuidados críticos predomina en preCPC (51 vs. 26 %; p < 0,005). (AU)

Introduction: The prevalence of heart failure is on the rise. In its advanced stage (AHF) the condition manifests with incapacitating symptoms. Exacerbations, frequent admissions, and high morbidity and mortality represent conditions amenable to palliative care. A cardiology palliative care (CPC) program was designed to monitor symptoms, deepen communication, establish advanced directives, and adjust therapeutic efforts. The goal of the study was to compare the care of patients who died from AHF before and after CPC program implementation. Material and methods: This was an observational, comparative study. CPC was offered to patients with AHF, and these subjects were compared to a control group without CPC because of unavailability (preCPC). In the statistical analysis categorical variables were evaluated using non-parametric tests. Continuous variables were compared using the Mann-Whithey U-test. Results: Seventy-seven patients were included in the preCPC group, and 65 in the CPC group. They all had similar demographic characteristics: age (median), 75 years; male gender, 70 %. A decrease in duration (27.3 vs. 7.2; p < 0.001) and in number of hospital admissions (2.64 vs. 1.51; p < 0.001) was found in the CPC group as compared to the control group. Invasive procedures within the final 5 days of life predominated in the preCPC group; assisted mechanical ventilation (52.7 % vs. 7.8 %; p < 0.001), hemodialysis (41 % vs. 5.5 %; p < 0.001), cardiopulmonary resuscitation (88.2 % vs. 11 %; p < 0.001), central vascular access (75.7 % vs. 26.5 %, p < 0.01), and use of inotropics (70.5 % vs. 20 %; p < 0.001). Non-invasive, comfort interventions predominated in the CPC group: palliative sedation (3 % vs. 25 %), opioid use (35 % vs. 58.3 %), deactivation of implantable cardiac defibrillator (0 vs. 37,5 %), and do-not-resuscitate orders (3 % vs. 77 %; p < 0.001). Mortality in critical care settings predominated in the preCPC group (51 % vs. 26 %; p < 0.005). (AU)

A Fluorescence-based High Throughput-Screening assay for the SARS-CoV RNA synthesis complex

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) emergence in 2003 introduced the first serious human coronavirus pathogen to an unprepared world. To control emerging viruses, existing successful anti(retro)viral therapies can inspire antiviral strategies, as conserved viral enzymes (eg., viral proteases and RNA-dependent RNA polymerases) represent targets of choice. Since 2003, much effort has been expended in the characterization of the SARS-CoV replication/transcription machinery. Until recently, a pure and highly active preparation of SARS-CoV recombinant RNA synthesis machinery was not available, impeding target-based high throughput screening of drug candidates against this viral family. The current Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic revealed a new pathogen whose RNA synthesis machinery is highly (>96% aa identity) homologous to SARS-CoV. This phylogenetic relatedness highlights the potential use of conserved replication enzymes to discover inhibitors against this significant pathogen, which in turn, contributes to scientific preparedness against emerging viruses. Here, we report the use of a purified and highly active SARS-CoV replication/transcription complex (RTC) to set-up a high-throughput screening of Coronavirus RNA synthesis inhibitors. The screening of a small (1,520 compounds) chemical library of FDA-approved drugs demonstrates the robustness of our assay and will allow to speed-up drug repositioning or novel drug discovery against the SARS-CoV-2. Principle of SARS-CoV RNA synthesis detection by a fluorescence-based high throughput screening assay O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/192005v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@e8122dorg.highwire.dtl.DTLVardef@18557org.highwire.dtl.DTLVardef@1d95362org.highwire.dtl.DTLVardef@f15222_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- A new SARS-CoV non radioactive RNA polymerase assay is described - The robotized assay is suitable to identify RdRp inhibitors based on HTS

Bone age assessment with conventional ultrasonography in healthy infants from 1 to 24 months of age.

BACKGROUND: Radiographic bone age determination is part of the routine evaluation of suspected growth disorders. Simplicity and low cost are its major advantages, but although the effective dose of ionizing radiation is low, it should be taken into consideration given its cumulative effect. OBJECTIVES: To assess the chronological ultrasonographic emergence of the ossification centers of the hand and wrist. MATERIALS AND METHODS: Cross-sectional study of healthy patients ages 1 to 24 months (n=498) from Buenos Aires, Argentina. All patients underwent ultrasonographic evaluation of the left hand and wrist to identify the different bone nuclei; a subgroup of infants had their nuclei measured (n=228). RESULTS: Girls showed an earlier emergence of the evaluated nuclei and a trend to a greater size than age-matched boys. Size-for-age relation showed linear increase. Carpal bones (capitate and hamate) were the first to appear, as early as from the first 3 months of life, an age gap not thoroughly present on the radiographic atlas developed by Greulich and Pyle. The distal epiphysis of the radius and the second metacarpophalangeal joint (index finger) followed in order of emergence. The proximal epiphysis of the first metacarpal bone (thumb) was the last to emerge and was infrequently found on boys at age 24 months. Overall, these findings are in accordance with the radiographic atlas. An ultrasonography atlas of the left hand and wrist was outlined for girls and boys. CONCLUSION: Conventional ultrasonography allows proper identification of the ossification centers of the hand and wrist and may become an innocuous follow-up tool for patients with growth disorders.

Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis: implications for the management of immunosuppression.

BACKGROUND: Risk factors including how changes in immunosuppression influence the occurrence of immune reconstitution syndrome (IRS) in solid organ transplant (SOT) recipients with cryptococcosis have not been fully defined. METHODS: SOT recipients with cryptococcosis were identified and followed for 12 months. IRS was defined based on previously proposed criteria. RESULTS: Of 89 SOT recipients, 13 (14%) developed IRS. Central nervous system (CNS) disease (adjusted odds ratio [AOR], 6.23; P = .03) and discontinuation of calcineurin inhibitor (AOR, 5.11; P = .02) were independently associated with IRS. Only 2.6% (1/13) of the patients without these risk factors developed IRS compared with 18.8% (6/32) with 1 risk factor, and 50% (6/12) with both risk factors (χ(2) for trend, P = .0001). Among patients with CNS disease, those with neuroimaging abnormalities (P = .03) were more likely to develop IRS, irrespective of serum or CSF cryptococcal antigen titers and fungemia. Graft rejection after cryptococcosis was observed in 15.4% (2/13) of the patients with IRS compared with 2.6% (2/76) of those without IRS (P = .07). CONCLUSIONS: We determined variables that pose a risk for IRS and have shown that discontinuation of calcineurin inhibitors was independently associated with 5-fold increased risk of IRS in transplant recipients with cryptococcosis.

Tuberculosis in solid-organ transplant recipients: disease characteristics and outcomes in the current era.

We determined the characteristics of posttransplant tuberculosis and the impact of rifampin-based antituberculosis regimens on outcomes in the current era. Patients comprised 64 transplant recipients with tuberculosis, divided into 2 consecutive cohorts: an earlier cohort (cases occurring from 2003 to 2007) and a later cohort (cases from 2008 to 2011). Patients from the later versus earlier era had tuberculosis develop later after transplant (odds ratio, 1.01; 95% CI, 1.00-1.02; P= .05), were more likely to be liver transplant recipients (odds ratio, 4.52; 95% CI, 1.32-15.53; P= .02), and were more likely to receive tacrolimus-based immunosuppression (odds ratio, 3.24; 95% CI, 1.14-9.19; P= .03). Mortality rate was 10% in the later cohort and 21% in the earlier cohort (P= .20). Rifampin-based treatment was less likely to be used in patients with prior rejection (P= .04). However, neither rejection rate (P= .71) nor mortality (P= .93) after tuberculosis differed between recipients who received rifampin and recipients who did not. Thus, notable changes have occurred in the epidemiological characteristics of tuberculosis in transplant recipients. Overall mortality rate has improved, with about 90% of the patients now surviving after tuberculosis.

Mycobacterium tuberculosis-associated immune reconstitution syndrome in solid-organ transplant recipients.

BACKGROUND: Incidence, characteristics, and risk factors for tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (IRS) in solid-organ transplant (SOT) recipients are not known. METHODS: Patients are composed of 64 consecutive SOT recipients with TB followed for 12 months. IRS was defined based on previously proposed criteria. RESULTS: IRS developed in 14% (9/64) of the patients, a median of 47 days after the use of anti-TB therapy. Liver versus other types of organ transplant recipients (adjusted odds ratio [OR], 6.11; 95% confidence interval [CI], 1.08-34.86), prior cytomegalovirus infection (adjusted OR, 5.65; 95% CI, 0.93-34.47), and rifampin use (adjusted OR, 4.56; 95% CI, 0.74-27) were associated with a higher risk of IRS. The presence of more than one factor (liver transplantation, cytomegalovirus infection, and rifampin use) when compared with none of these factors conferred a 19-fold increase in the risk of IRS (P=0.01). Mortality at 1 year after diagnosis was 33.3% in patients with IRS and 17.2% in those without IRS (P=0.31). CONCLUSIONS: IRS was documented in 14% of the SOT recipients with TB. We determined clinically identifiable factors that may be useful in assessing the risk of tuberculosis-associated posttransplantation IRS.

Effect of linezolid compared with glycopeptides in methicillin-resistant Staphylococcus aureus severe pneumonia in piglets.

OBJECTIVES: To investigate if compared with glycopeptides, antimicrobial therapy (AMT) with linezolid (LZD) improves the outcome in methicillin-resistant Staphylococcus aureus (MRSA) experimental pneumonia in mechanically ventilated piglets. METHODS: The MRSA minimal inhibitory concentration (MIC) was 0.5 for vancomycin (VAN), 0.25 for teicoplanin (TEI), and 2.0 microg/mL for LZD was inoculated in Largewhite-Landrace piglets divided into five groups. One group (n = 6) did not receive mechanical ventilation (MV) or AMT. Those in the remaining groups received MV and VAN (n = 9), TEI (n = 7), LZD (n = 9), or no AMT (n = 7). Plasma and BAL tumor necrosis factor-alpha, interleukin-6, and C-reactive protein (CRP) concentrations, postmortem lung pathology, cultures (lung, blood, and BAL) and plasma, epithelial lining fluid (ELF), and lung antibiotic concentrations were evaluated. MEASUREMENTS AND MAIN RESULTS: All piglets developed severe pneumonia; lung pathology score was lower in those receiving LZD vs those receiving glycopeptides (p = 0.049) or no AMT (p = 0.037). Serum CRP and serum and BAL cytokines increased; there were no differences between the groups. Fourteen died spontaneously at 44.4 +/- 16.8 h; the remaining 24 were killed after 72 to 96 h. The concentrations of the antimicrobial agents tested in 15 piglets were higher than the MIC for the three antimicrobial agents in peak and trough plasma, ELF, and lung specimens. Survival at 72 h was higher in the LZD comparing with the no-AMT group. CONCLUSIONS: Inoculation produced severe MRSA pneumonia. LZD AMT was associated with lower pathology score, better survival, and a trend to better clearance of MRSA, not attributable exclusively to pharmacokinetic or pharmacodynamic reasons.