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The atomic mobility in liquid pure gallium and a gallium-nickel alloy with 2 at% of nickel is studied experimentally by incoherent quasielastic neutron scattering. The integral diffusion coefficients for all-atom diffusion are derived from the experimental data at different temperatures. DFT-basedab-initiomolecular dynamics (MD) is used to find numerically the diffusion coefficient of liquid gallium at different temperatures, and numerical theory results well agree with the experimental findings at temperatures below 500 K. Machine learning force fields derived fromab-initiomolecular dynamics (AIMD) overestimate within a small 6% error the diffusion coefficient of pure gallium within the genuine AIMD. However, they better agree with experiment for pure gallium and enable the numerical finding of the diffusion coefficient of nickel in the considered melted alloy along with the diffusion coefficient of gallium and integral diffusion coefficient, that agrees with the corresponding experimental values within the error bars. The temperature dependence of the gallium diffusion coefficientDGa(T)follows the Arrhenius law experimentally for all studied temperatures and below 500 K also in the numerical simulations. However,DGa(T)can be well described alternatively by an Einstein-Stokes dependence with the metallic liquid viscosity following the Arrhenius law, especially for the MD simulation results at all studied temperatures. Moreover, a novel variant of the excess entropy scaling theory rationalized our findings for gallium diffusion. Obtained values of the Arrhenius activation energies are profoundly different in the competing theoretical descriptions, which is explained by different temperature-dependent prefactors in the corresponding theories. The diffusion coefficient of gallium is significantly reduced (at the same temperature) in a melted alloy with natural nickel, even at a tiny 2 at% concentration of nickel, as compared with its pure gallium value. This highly surprising behavior contradicts the existing excess entropy scaling theories and opens a venue for further research.
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OBJECTIVES: Few studies have assessed cognitive impairment among healthy people living with HIV (PLWH) who are stable on antiretroviral treatment (ART) in sub-Saharan Africa. METHODS: We conducted a cross-sectional study among a random sample of stable adult PLWH from rural Tanzania on ART for more than 1 year and without immunological failure or pre-existing neurological disease. We evaluated the prevalence and risk factors for neurocognitive impairment (NCI), assessed through neuropsychological tests, functional and depression questionnaires and defined as a mean Z-score ≤ -1 in two or more cognitive domains. RESULTS: Among 243 participants [median age = 44.3 years (interquartile range: 36-52] and 71% female] we found a rate of NCI of 19.3% (95% confidence interval: 14.8-24.8%). Memory and psychomotor domains demonstrated the highest impairment. Independent predictors of NCI were age and self-reported alcohol use. Other classical risk factors were not associated with HIV-associated NCI. CONCLUSION: Despite effective ART roll-out, NCI remained a prevalent condition in this healthy rural Tanzanian population of PLWH on ART. Age and alcohol use were key risk factors.
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Infecciones por VIH , Adulto , Antirretrovirales/uso terapéutico , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Masculino , Encuestas y Cuestionarios , Tanzanía/epidemiologíaRESUMEN
BACKGROUND: By understanding prognostic biomarkers, we gain insights into disease biology and may improve design, conduct, and data analysis of clinical trials and real-world data. In this context, we used the Flatiron Health Electronic Health Record-derived deidentified database that provides treatment outcome and biomarker data from >280 oncology centers in the USA, organized into 17 cohorts defined by cancer type. PATIENTS AND METHODS: In 122 694 patients, we analyzed demographic, clinical, routine hematology, and blood chemistry parameters within a Cox proportional hazard framework to derive a multivariable prognostic risk model for overall survival (OS), the 'Real wOrld PROgnostic score (ROPRO)'. We validated ROPRO in two independent phase I and III clinical studies. RESULTS: A total of 27 variables contributed independently and homogeneously across cancer indications to OS. In the largest cohort (advanced non-small-cell lung cancer), for example, patients with elevated ROPRO scores (upper 10%) had a 7.91-fold (95% confidence interval 7.45-8.39) increased death hazard compared with patients with low scores (lower 10%). Median survival was 23.9 months (23.3-24.5) in the lowest ROPRO quartile Q1, 14.8 months (14.4-15.2) in Q2, 9.4 months (9.1-9.7) in Q3, and 4.7 months (4.6-4.8) in Q4. The ROPRO model performance indicators [C-index = 0.747 (standard error 0.001), 3-month area under the curve (AUC) = 0.822 (0.819-0.825)] strongly outperformed those of the Royal Marsden Hospital Score [C-index = 0.54 (standard error 0.0005), 3-month AUC = 0.579 (0.577-0.581)]. We confirmed the high prognostic relevance of ROPRO in clinical Phase 1 and III trials. CONCLUSIONS: The ROPRO provides improved prognostic power for OS. In oncology clinical development, it has great potential for applications in patient stratification, patient enrichment strategies, data interpretation, and early decision-making in clinical studies.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estudios de Cohortes , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: Widespread access to antiretroviral therapy (ART) has substantially increased life expectancy in sub-Saharan African countries. As a result, the rates of comorbidities and use of co-medications among people living with HIV are increasing, necessitating a sound understanding of drug-drug interactions (DDIs). We aimed to assess the prevalence and management of DDIs with ART in a rural Tanzanian setting. METHODS: We included consenting HIV-positive adults initiating ART in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) between January 2013 and December 2016. DDIs were classified using www.hiv-druginteractions.org as red (contra-indicated), amber (potential clinical relevance requiring dosage adjustment/monitoring), yellow (weak clinical significance unlikely to require further management) or green (no interaction). We assessed management of amber DDIs by evaluating monitoring of laboratory or clinical parameters, or changes in drug dosages. RESULTS: Of 2069 participants, 1945 (94%) were prescribed at least one co-medication during a median follow-up of 1.8 years. Of these, 645 (33%) had at least one potentially clinically relevant DDI, with the highest grade being red in nine (< 1%) and amber in 636 (33%) participants. Of the 23 283 prescriptions, 19 (< 1%) and 1745 (7%) were classified as red and amber DDIs, respectively. Overall, 351 (2%) prescriptions were red DDIs or not appropriately managed amber DDIs. CONCLUSIONS: Co-medication use was common in this rural sub-Saharan cohort. A third of participants had DDIs requiring further management. Of the 9% of participants with not appropriately managed DDIs, most were with cardiovascular and analgesic drugs. This highlights the importance of physicians' awareness of DDIs for their recognition and management.
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Antirretrovirales/administración & dosificación , Interacciones Farmacológicas , Infecciones por VIH/tratamiento farmacológico , Adolescente , Adulto , Antirretrovirales/uso terapéutico , Comorbilidad , Cálculo de Dosificación de Drogas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Población Rural , Tanzanía/epidemiología , Adulto JovenRESUMEN
Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to improve the management of SOT recipients.
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Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/epidemiología , Rechazo de Injerto/etiología , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias , Receptores de Trasplantes/estadística & datos numéricos , Antibacterianos/uso terapéutico , Estudios de Casos y Controles , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/microbiología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/patología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Suiza/epidemiologíaRESUMEN
OBJECTIVES: Antibacterial resistance is emerging in patients undergoing haematopoietic stem cell transplantation (HSCT), and most data on the epidemiology of bloodstream infections (BSI)-causing pathogens come from retrospective single-centre studies. This study sought to investigate trends in the epidemiology of BSI in HSCT patients from a prospective multicentre cohort. METHODS: We investigated changes in the incidence of causative organisms of BSI during neutropenia among adult HSCT patients for 2002-2014. The data were collected from a prospective cohort for infection surveillance in 20 haematologic cancer centres in Germany, Austria and Switzerland (ONKO-KISS). RESULTS: A total of 2388 of 15 181 HSCT patients with neutropenia (1471 allogeneic (61.6%) and 917 autologous (38.4%) HSCT) developed BSI (incidence 15.8% per year). The incidence of Gram-negative BSI increased over time both in patients after allogeneic HSCT (allo-HSCT) and autologous HSCT (auto-HSCT). BSI caused by Escherichia coli in allo-HSCT patients increased from 1.1% in 2002 to 3.8% in 2014 (3/279 vs. 31/810 patients, p <0.001), and the incidence of BSI caused by enterococci increased from 1.8% to 3.3% (5 vs. 27 patients, p <0.001). In contrast, the incidence of BSI due to coagulase-negative staphylococci decreased in allo-HSCT patients from 8.2% to 5.1%, (23 vs. 40 patients, p <0.001) and in auto-HSCT patients from 7.7% to 2.0% (13/167 vs. 30/540 patients; p = 0.028 for period 2002-2011). No significant trends were observed for the incidence of BSI due to methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci or extended-spectrum ß-lactamase-producing Enterobacteriaceae. The BSI case fatality remained unchanged over the study period (total of 477 fatalities, 3.1%). CONCLUSIONS: The incidence of Gram-negative BSI significantly increased over time in this vulnerable patient population, providing evidence for reevaluating empiric therapy for neutropenic fever in HSCT patients.
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Bacteriemia , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Neutropenia , Adulto , Bacteriemia/epidemiología , Bacteriemia/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/epidemiología , Neutropenia/microbiología , Estudios Prospectivos , Estudios Retrospectivos , Trasplante Homólogo/estadística & datos numéricosRESUMEN
OBJECTIVES: Rapid identification of pathogens directly from positive blood cultures (BC) in combination with an antimicrobial stewardship programme (ASP) is associated with improved antibiotic treatment and outcomes, but the effect of each individual intervention is less clear. The current study investigated the impact of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) versus conventional identification on antibiotic management in a setting with a well-established ASP and low resistance rates. METHODS: In this single-centre open label, controlled clinical trial 425 patients with positive BCs were allocated by weekday during a 1-year period to either MALDI-TOF directly from positive BCs or conventional processing. ASP was identical throughout the study period. The primary outcome was duration of intravenous antimicrobial therapy and was analysed in an intention-to-treat approach. RESULTS: In all, 368 patients were analysed (MALDI-TOF n = 168; conventional n = 200) with similar baseline characteristics. Mean duration of intravenous antimicrobial therapy (12.9 versus 13.2 days, p 0.9) and length of stay (16.1 versus 17.9 days, p 0.3) were comparable. In the clinically significant bloodstream infection subgroup (n = 242) mean time from Gram-stain to active treatment was significantly shorter (3.7 versus 6.7 h, p 0.003). Admission to the intensive care unit after bloodstream infection onset was less frequent in the MALDI-TOF group (23.1 versus 37.2%, p 0.02). CONCLUSIONS: Rapid identification of contaminated BCs (n = 126) resulted in a shorter duration of intravenous antimicrobial therapy (mean 4.8 versus 7.5 days, p 0.04). Rapid identification using MALDI-TOF directly from positive BCs did not impact on duration of intravenous antimicrobial therapy, but provided fast and reliable microbiological results and may improve treatment quality in the setting of an established ASP.
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Cultivo de Sangre , Sepsis/diagnóstico , Sepsis/etiología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Anciano , Anciano de 80 o más Años , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Cultivo de Sangre/métodos , Comorbilidad , Ensayos Clínicos Controlados como Asunto , Farmacorresistencia Microbiana , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Sepsis/tratamiento farmacológico , Sepsis/epidemiología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: In this study we aimed to analyse the association between use of daptomycin and MICs of daptomycin in Enterococcus faecium bacteraemia. METHODS: We prospectively enrolled patients aged ≥18 years with E. faecium bacteraemia hospitalized at the University Hospital Basel from 2008 to 2014. We determined daptomycin MICs by Etests and used pulsed field gel electrophoresis to determine clonal relatedness. We recorded the defined daily dosages of daptomycin (DDDs) per 100 patient-days and clinical data from charts. We correlated daptomycin MIC with use of daptomycin in patients with recurrence/persistence. RESULTS: In 195 E. faecium bacteraemias originating from 162 patients the median MIC for daptomycin was 2 mg/L (IQR 2-3); 30% (15.4%) isolates had a MIC ≥4 mg/L and 6 (3.1%) were resistant (MIC >4 mg/L) according to CLSI criteria. The usage of daptomycin increased more than four-fold from 0.36 DDDs/100 patient-days in 2008 to 1.6 in 2014. In 13 of 28 (42.9%) patients with a relapsing or persisting bacteraemia, the daptomycin MIC of the second isolate increased from a median of 2.0 to 2.5 mg/L (p 0.010); 3/13 (23.1%) developed resistance. All patients with the same clone in the first and second episode and an increase of daptomycin MIC had been treated with daptomycin (6/6 versus 1/7 p 0.005). CONCLUSIONS: Daptomycin MICs and Daptomycin usage increased over time. On an individual patient level daptomycin exposure was associated with an increased MIC in subsequent bacteraemia episodes. Diversity did not indicate a clonal origin and argues for a de novo development of resistance.
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Antibacterianos/farmacología , Bacteriemia , Daptomicina/farmacología , Farmacorresistencia Bacteriana , Enterococcus faecium/efectos de los fármacos , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Adulto , Anciano , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Comorbilidad , Daptomicina/efectos adversos , Daptomicina/uso terapéutico , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Vigilancia de la Población , Estudios RetrospectivosRESUMEN
Success rates for treatment regimens involving retention of an infected implant are conflicting and failure rates of up to 80% have been reported. We aimed to validate a proposed treatment algorithm, based on strict selection criteria, by assessing long-term outcome of treatment for orthopaedic device-related infection (ODRI) with retention. From January 1999 to December 2009, all patients diagnosed with ODRI at the University Hospital Basel, Switzerland were eligible for treatment with open surgical debridement, implant-retention and antibiotics, if duration of clinical symptoms was ≤3 weeks, the implant was stable, the soft-tissue had no abscess or sinus tract, and the causative pathogen was susceptible to antimicrobial agents with activity against surface-adhering microorganisms. Antimicrobial treatment was administered according to a predefined algorithm. The primary outcome was treatment failure after 2-year follow up. A total of 455 patients were diagnosed with an ODRI, of whom 233 (51.2%) patients were eligible for treatment involving implant-retention. Causative pathogens were mainly Staphylococcus aureus (41.6%) and coagulase-negative staphylococci (33.9%). Among patients with ODRIs related to prostheses, failure was documented in 10.8% (12/111) and in patients with ODRIs related to osteosyntheses, failure occurred in 9.8% (12/122) after 2 years of follow up. In all, 90% of ODRIs were successfully cured with surgical debridement and implant-retention in addition to long-term antimicrobial therapy according to a predefined treatment algorithm: if patients fulfilled strict selection criteria and there was susceptibility to rifampin for Gram-positive pathogens and ciprofloxacin for Gram-negative pathogens.
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Algoritmos , Procedimientos Ortopédicos/efectos adversos , Retención de la Prótesis , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Ciprofloxacina/farmacología , Desbridamiento , Femenino , Hospitales Universitarios , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Infecciones Relacionadas con Prótesis/microbiología , Rifampin/farmacología , Suiza , Resultado del TratamientoRESUMEN
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Various disease-related and patient-related factors have been shown to influence the course of the disease. The aim of this study was to identify novel biomarkers of significant clinical relevance. Pretreatment CD19-separated lymphocytes (n=237; discovery set) and peripheral blood mononuclear cells (n=92; validation set) from the REACH trial, a randomized phase III trial in relapsed CLL comparing rituximab plus fludarabine plus cyclophosphamide with fludarabine plus cyclophosphamide alone, underwent gene expression profiling. By using Cox regression survival analysis on the discovery set, we identified inositol polyphosphate-5-phosphatase F (INPP5F) as a prognostic factor for progression-free survival (P<0.001; hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.35-1.98) and overall survival (P<0.001; HR, 1.47; 95% CI, 1.18-1.84), regardless of adjusting for known prognostic factors. These findings were confirmed on the validation set, suggesting that INPP5F may serve as a novel, easy-to-assess future prognostic biomarker for fludarabine-based therapy in CLL.
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Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/análisis , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Monoéster Fosfórico Hidrolasas/biosíntesis , Vidarabina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Inositol Polifosfato 5-Fosfatasas , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Monoéster Fosfórico Hidrolasas/análisis , Pronóstico , Modelos de Riesgos Proporcionales , Transcriptoma , Vidarabina/uso terapéuticoRESUMEN
Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.
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Infecciones por Citomegalovirus/terapia , Farmacorresistencia Viral Múltiple , Trasplante de Células Madre Hematopoyéticas , Huésped Inmunocomprometido , Traslado Adoptivo , Antivirales/uso terapéutico , Terapia Combinada , Infecciones por Citomegalovirus/inmunología , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In vivo T-cell depletion with anti-thymocyte globulin (ATG) can attenuate GvHD but may increase infection and relapse risks. ATG-Fresenius (ATG-F) at a dose of 60 mg/kg was standard GvHD prophylaxis in unrelated donor hematopoietic stem cell transplantation (HSCT) at our institution. We changed to an incremental reduced dose regimen of 35 mg/kg and extended ATG prophylaxis to include older matched-related donor transplants considered to be at higher risk of GvHD. A total of 265 adults with hematological malignancies receiving a first allogeneic HSCT after myeloablative conditioning between 2009 and 2014 were analyzed in this cohort study. Patients had either received higher dose (n=32) or lower dose ATG-F (n=88) or no ATG (n=145). ATG-F was associated with slower engraftment and less chronic GvHD, whereas no effect was noted on acute grade II-IV GvHD and relapse incidence. Transplant-related mortality (TRM) was lower and survival higher with lower dose, but not with higher dose ATG-F. Both ATG-F groups were associated with more viral reactivation, viral disease and bacterial blood stream infection, but not invasive fungal infection, and with slower immune reconstitution. The recently adopted strategy of using lower doses of ATG-F in unrelated and older age-related donor HSCT appears to reduce TRM without increasing disease relapse, leading to slightly enhanced survival.
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Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Acondicionamiento Pretrasplante/mortalidad , Trasplante Homólogo/mortalidad , Adulto JovenRESUMEN
This case report describes the simultaneous manifestation of acute necrotizing encephalopathy in 2 consanguineous patients after infection with influenza B based on the autosomal dominant missense mutation of the RANBP2-gene. Differential diagnosis of acute encephalopathy, clinical and radiological clues, and treatment strategies are outlined.
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INTRODUCTION: In immunosuppressed hosts, rapid identification of microorganisms of bloodstream infections is crucial to ensuring effective antimicrobial therapy. Conventional culture requires up to 72 h from sample collection to pathogen identification. METHODS: We used the SepsiTyper Kit and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF; Microflex, Bruker) directly from positive blood culture (BacT/ALERT 3D, FN/FA vials; bioMérieux) in comparison to standard culture methodology (VITEK 2; bioMérieux) for species identification. RESULTS: A total of 62 consecutive positive blood cultures from immunosuppressed patients (solid organ or hematopoietic transplant recipients, or with febrile neutropenia) were analyzed. Culture yielded gram-negative bacteria (GNB) in 27/62 (43.5%) and gram-positive (GPB) in 35/62 (56.5%) vials. For GNB, the predominant species identified by MALDI-TOF and confirmed by VITEK were Escherichia coli (16/16 correctly identified) and Enterobacter cloacae (4/4), with a sensitivity and specificity of 92.6% and 100%, respectively. For GPB, predominant species were Staphylococcus aureus (3/3), coagulase-negative staphylococci (12/24), and Enterococcus faecium (6/6) with a sensitivity of 100%, 60%, and 100%, respectively. The median time from blood collection to species identification was 27.4 h with MALDI-TOF identification and 46.6 h with conventional methodology. CONCLUSION: Using MALDI-TOF directly from positive blood cultures allowed a shorter time to identification with high sensitivity and specificity in immunosuppressed patients.
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Bacteriemia/diagnóstico , Enfermedades Transmisibles/diagnóstico , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Estudios de Cohortes , Enfermedades Transmisibles/microbiología , Humanos , Huésped Inmunocomprometido , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Screening for Pseudomonas aeruginosa is recommended to guide empirical antimicrobial therapy in patients on high-risk units. However, evidence for this approach is scarce. We therefore screened 1310 patients with severe haematologic diseases for P. aeruginosa colonization at admission: 108 (8.2%) were positive, but only nine (0.7%; six with the same clone as in the screening isolate) subsequently developed a P. aeruginosa bloodstream infection (positive predictive value of screening, 8.6%; negative predictive value of screening, 99.5%). Routine screening for P. aeruginosa at admission did not sufficiently predict subsequent bloodstream infections caused by P. aeruginosa.
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Portador Sano/diagnóstico , Portador Sano/microbiología , Pruebas Diagnósticas de Rutina/métodos , Enfermedades Hematológicas/complicaciones , Tamizaje Masivo/métodos , Infecciones por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/aislamiento & purificación , Bacteriemia/epidemiología , Bacteriemia/microbiología , Humanos , Admisión del Paciente , Valor Predictivo de las Pruebas , Estudios Prospectivos , Infecciones por Pseudomonas/microbiologíaRESUMEN
BACKGROUND: Detection of fungal DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is challenging due to degradation of DNA and presence of PCR inhibitors in these samples. We analyzed FFPE samples of 26 patients by panfungal PCR and compared the results to the composite diagnosis according to the European Organization for Research and Treatment of Cancer (EORTC) criteria. Additionally we analyzed the quality of human and fungal DNA and their level of age-dependent degradation, as well as the existence of PCR inhibition in these tissue samples. METHODS: We evaluated two 45-cycle panfungal PCR tests that target the internal transcribed spacer 2 (ITS2) as well as the ITS1-5.8S-ITS2 (ITS1-2) region. The PCRs were applied to 27 FFPE specimens from 26 patients with proven invasive fungal disease (IFD), and one patient with culture and histologically negative but PCR-positive fungal infection collected at our institution from 2003 to 2010. Quality of DNA in FFPE tissue samples was evaluated using fragments of the beta-globin gene for multiplex PCR, inhibition of PCR amplification was evaluated by spiking of C. krusei DNA to each PCR premix. RESULTS: In 27 FFPE samples the ITS2 PCR targeting the shorter fragment showed a higher detection rate with a sensitivity of 53.8% compared to the ITS1-2 fragment (sensitivity 38%). Significant time-dependent degradation of human DNA in FFPE sample extracts was detected based on partial beta-globin gene amplification which was not in correlation to successful panfungal PCR identification of fungal organisms. The analytical sensitivity of both assays compared with culture was 60 CFU/ml of a Candida krusei reference strain. The performance of the two tests in an Aspergillus proficiency panel of an international external quality assessment programme showed considerable sensitivity. CONCLUSION: Panfungal diagnostic PCR assays applied on FFPE specimens provide accurate identification of molds in highly degraded tissue samples and correct identification in samples stored up to 7 years despite sensitivity limitations, mainly caused by partial PCR inhibition and DNA degradation by formalin.
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Aspergilosis/diagnóstico , ADN de Hongos/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Aspergilosis/microbiología , Aspergillus/genética , ADN de Hongos/genética , Fijadores/química , Formaldehído/química , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Tipificación Micológica , Adhesión en Parafina , Sensibilidad y Especificidad , Fijación del TejidoRESUMEN
In spite of the self-limiting natural course of infantile haemangiomas of the eyelids and orbit, the effects of amblyopia, compression of the optic nerve, and impairment of the aesthetic appearance may develop. Since the serendipitous discovery of the effects of propranolol, a non-selective beta-blocker, on infantile haemangioma in 2008, it has largely replaced the former standard treatments with corticosteroids, laser or surgical procedures. This review discusses the pathogenesis, classification, indication for treatment, and treatment options for infantile haemangiomas. In addition, the results of patients with infantile haemangiomas of the eyelids and orbit treated with systemic propranolol are shown. With additional confirmation of data, including a positive effect-risk-analysis, propranolol will potentially replace high-dose corticosteroids and surgery in the treatment of infantile haemangiomas in the eyelids and orbit. Further clinical studies are necessary to optimise the dosage, treatment period, and application modalities (oral or topical). In the future, propranolol accompanied with paediatric-cardiological monitoring should emerge as the first-line therapy for problematic infantile haemangiomas.
Asunto(s)
Hemangioma/tratamiento farmacológico , Hemangioma/patología , Neoplasias Orbitales/tratamiento farmacológico , Neoplasias Orbitales/patología , Propranolol/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Antagonistas Adrenérgicos beta/uso terapéutico , Femenino , Humanos , Recién Nacido , MasculinoRESUMEN
Sternal osteomyelitis after median sternotomy is associated with considerable morbidity and mortality. Combined with radical debridement, muscle and less frequently omentum flaps are used to reconstruct the resulting defects. In this study, we present our experience with the fasciocutaneous superior epigastric artery perforator (SEAP) flap for defect closure. After resection of the entire sternum, including the costochondral arches and the sternoclavicular joints, the repair of the defect was performed with the perforator flap without any re-stabilisation of the thoracic wall. A consecutive series of nine patients with a mean age of 69 ± 6 years were reconstructed with the SEAP flap. The mortality rate was zero. One patient developed a mediastinal haematoma and required five re-interventions by the cardiothoracic surgeons and thereafter a revision to close a small-wound dehiscence at the tip of the flap. Another two patients developed partial necrosis of the flap that could be managed conservatively. One patient had a revision for a seroma on the donor site, resulting in a 100% closure rate of the defect; there were revisions in two out of nine patients. The underlying infection was controlled by debridement, antibiotic therapy and flap closure in all cases. The overall success of the procedure was satisfactory; however, the local complication rate was relatively high with three out of nine patients on the flap side and one of nine on the donor site. Major advantages of the perforator flap in this highly morbid patient cohort are that the operation is relatively quick, muscle tissue is spared and re-education facilitated.
Asunto(s)
Osteomielitis/cirugía , Colgajo Perforante/efectos adversos , Esternón/cirugía , Infección de la Herida Quirúrgica/etiología , Anciano , Arterias Epigástricas , Hematoma/etiología , Humanos , Persona de Mediana Edad , Necrosis/etiología , Colgajo Perforante/irrigación sanguínea , Colgajo Perforante/patología , Reoperación , Seroma/etiología , Infección de la Herida Quirúrgica/terapiaRESUMEN
BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.