Consensus statement of the Spanish Society of Internal Medicine and the Spanish Society of Medical Oncology on secondary thromboprophylaxis in patients with cancer

Up to 20% of cancer patients will develop some manifestation of venous thromboembolic disease (VTD) during their clinical course. VTD greatly impacts morbidity, mortality, quality of life and pharmaceutical expenditure. In addition, both thrombotic relapse and major haemorrhages derived from VTD treatment are more likely in oncological patients. To make the decision to establish secondary thromboprophylaxis as an indefinite treatment in these patients, it is important to review all the risk factors involved, whether related to the disease, the patient or the prior thrombotic event. The objectives of this consensus of the Spanish Society of Internal Medicine (Sociedad Española de Medicina Interna—SEMI) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica—SEOM) are to establish recommendations that help assess the risk of recurrence of VTD and haemorrhagic risk in patients with cancer, as well as to analyse the evidence that exists on the currently available drugs, which will allow the establishment of a protocol for shared decision-making with the informed patient (AU)

Consensus statement of the Spanish Society of Internal Medicine and the Spanish Society of Medical Oncology on secondary thromboprophylaxis in patients with cancer.

Up to 20% of cancer patients will develop some manifestation of venous thromboembolic disease (VTD) during their clinical course. VTD greatly impacts morbidity, mortality, quality of life and pharmaceutical expenditure. In addition, both thrombotic relapse and major haemorrhages derived from VTD treatment are more likely in oncological patients. To make the decision to establish secondary thromboprophylaxis as an indefinite treatment in these patients, it is important to review all the risk factors involved, whether related to the disease, the patient or the prior thrombotic event. The objectives of this consensus of the Spanish Society of Internal Medicine (Sociedad Española de Medicina Interna-SEMI) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) are to establish recommendations that help assess the risk of recurrence of VTD and haemorrhagic risk in patients with cancer, as well as to analyse the evidence that exists on the currently available drugs, which will allow the establishment of a protocol for shared decision-making with the informed patient.

Elevation of serum ferritin levels for predicting a poor outcome in hospitalized patients with influenza infection.

OBJECTIVES: There is increasing evidence that ferritin is a key marker of macrophage activation, but its potential role in influenza infection remains unexplored. Our aim was to assess whether hyperferritinaemia (ferritin ≥500 ng/mL) could be a marker of poor prognosis in hospitalized patients with confirmed influenza A infection. METHODS: We prospectively recruited all hospitalized adult patients who tested positive for the influenza A rRT-PCR assay performed on respiratory samples in two consecutive influenza periods (2016-17 and 2017-18). Poor outcome was defined as the presence of at least one of the following: respiratory failure, admission to the intensive care unit, or in-hospital mortality. RESULTS: Among 494 patients, 68 (14%) developed poor outcomes; 112 patients (23%) had hyperferritinaemia (39/68, 57% in the poor-outcome group versus 73/426, 17% in the remaining patients, p < 0.0001). Median serum ferritin levels were significantly higher in the subgroup of patients with poor outcomes (609 ng/mL, range 231-967 versus 217 ng/mL, range 140-394, p < 0.0001). In multivariate analysis, hyperferritinaemia was associated with a five-fold increase in the odds ratio of developing poor outcome. After adjusting for classic influenza risk factors, ferritin remained as a significant predictive factor in all exploratory models. Ferritin levels had a good discriminative capacity with an area under the ROC curve of 0.72 (95% confidence interval (CI) 0.65-0.8, p < 0.001) and an overall diagnostic accuracy for predicting poor outcome of 79.3% (95%CI 75.4-82.7%). CONCLUSIONS: Serum ferritin may discriminate a subgroup of patients with influenza infection who have a higher risk of developing a poor outcome.

Impact of severe hematological abnormalities in the outcome of hospitalized patients with influenza virus infection.

Although hematological abnormalities have been described among patients with influenza virus infection, little is known about their impact on the outcome of the patients. The aim of this study was to assess the frequency and clinical impact of severe hematological abnormalities in patients with confirmed influenza virus infection. This was an observational retrospective study including all adult patients with diagnosis of influenza virus infection hospitalized from January to May 2016 in our institution. Influenza virus infection was diagnosed by means of rRT-PCR assay performed on respiratory samples. Poor outcome was defined as a composite endpoint in which at least one of the following criteria had to be fulfilled: (a) respiratory failure, (b) SOFA ≥2, or (c) death. Two hundred thirty-nine patients were included. Applying the HLH-04 criteria for the diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin ≤9 g/dl, platelets <100,000/µl or neutrophils <1,000/µl) were present in 51 patients (21%). Patients with hematological abnormalities showed higher SOFA scores, respiratory failure, septic shock and in-hospital mortality than the remaining patients. The composite endpoint was present in 33.3% in the cytopenias group vs. 13.3% in the group without cytopenias (p=0.001). In a multivariate analysis, variables associated with the composite endpoint were: use of steroids prior to present admission (OR: 0.12; 95% CI: 0.015-0.96, p=0.046), presence of any hematological abnormality (OR: 3.54; 95% CI:1.66-7.51, p= 0.001), and LDH>225 U/l (OR:4.45; CI:1-19.71, p=0.049). Hematological abnormalities are not uncommon among hospitalized patients with influenza virus infection, and they are associated with a poorer outcome.

Si fiebre, ¿hemocultivos? / Blood cultures when fever?

Varón de 78 años, con antecedentes de hipertensión arterial y diabetes mellitus, remitido a urgencias desde su residencia por deterioro del estado general y caídas frecuentes en la última semana. Dos semanas antes precisó sondaje vesical, que fue traumático y de forma profiláctica se prescribió ciprofloxacino. En la exploración física destaca desorientación, TA90/40mmHg, frecuencia cardíaca 120lpm, T.a 37,3 1C, 24 respiraciones por minuto y dolor a la palpación en hipocondrio izquierdo. En el electrocardiograma se objetiva taquicardia sinusal. Al canalizar la vía periférica se nos pregunta: ¿le saco hemocultivos?(AU)

A 78-year-old man was refrerred from his residency where he lives to the emergency division due to general deterioration and frequent falls in the last week. His personal history is remarkable for arterial hypertension and diabetes. Two weeks before he needed a vesical catheterism that was traumatic and profilactic ciprofloxacin was prescriped. On phisical exploration he appears desoriented, blodd pressure is 9/40mmHg, cardiac rythm 120 beats per minute, temperature 37,3°C and 24 respirations per minute. He appears to have pain on his upper left abdomen cuadrant. When the nurse gets a peripheral vein she asks, ¿should I obtain hemocultures?(AU)

[Blood cultures when fever?]. / Si fiebre, ¿hemocultivos?

A 78-year-old man was referred from his residency where he lives to the emergency division due to general deterioration and frequent falls in the last week. His personal history is remarkable for arterial hypertension and diabetes. Two weeks before he needed a vesical catheterism that was traumatic and profilactic ciprofloxacin was prescribed. On physical exploration he appears disoriented, blood pressure is 9/40 mm Hg, cardiac rythm 120 beats per minute, temperature 37,3 °C and 24 respirations per minute. He appears to have pain on his upper left abdomen cuadrant. When the nurse gets a peripheral vein she asks, ¿should I obtain hemocultures?

Infección fúngica invasiva en una paciente inmunocomprometida / Invasive fungal infections in immunocompromised patients

No disponible

Incidence, clinical characteristics and risk factors of late infection in solid organ transplant recipients: data from the RESITRA study group.

Information describing the incidence and clinical characteristics of late infection (LI) in solid organ transplantation (SOT) is scarce. The aim of this study was to define the incidence, clinical characteristics and risk factors for LI (>6 months) as compared with infection in the early period (<6 months) after SOT. By the online database of the Spanish Network of Infection in Transplantation (RESITRA) we prospectively analyzed 2702 SOT recipients from September 2003 to February 2005. Univariate and multivariate analysis using logistic regression were performed to calculate the risk factors associated with the development of LI. A total of 131 patients developed 176 LI episodes (8%). Global incidence of LI was 0.4 per 1000 transplant-days, ranging from 0.3/1000 in kidney transplants to 1.4 in lung transplants. Independent risk factors for LI in were: acute rejection in the early period (OR 1.5; CI 95%: 1.1-2.3), chronic graft malfunction (OR 2; CI 95%: 1.4-3), re-operation (OR 1.9; CI 95%: 1.3-2.8) relapsing viral infection apart from CMV (OR 1.9; CI 95%: 1.1-3.5), previous bacterial infection (OR 1.8; CI 95%: 1.2-2.6) and lung transplantation (OR 4.5; CI 95%: 2.6-7.8). Severe LI occurs in a subgroup of high-risk SOT recipients who deserve a more careful follow-up and could benefit from prolonged prophylactic measures similar to that performed in the early period after transplantation.

[Individualized evaluation of the risk of infections in the oncohematologic patient]. / Evaluación individualizada del riesgo de infecciones en el paciente oncohematológico.

In order to take the best approach to infection in the oncohematologic patient with fever, it is important to know not only how profound the neutropenia is and how long the patient has had it, but also the characteristics of the underlying disease, the immunosuppressive therapy received and the type of hematopoietic stem/progenitor cell transplantation performed. Moreover, is important to consider if these patients have any personal or familial history of infectious diseases. All these aspects let us calculate the net state of immunosuppression and the risk of infection, and provide us with information about the most probable etiology in each case and the best prophylaxis and treatment. In this study we review the more important advances in chemotherapy in recent years that will make it necessary in the future to change our prophylactic guidelines for more effective prevention of infection in the oncohematologic patient.

Evaluación individualizada del riesgo de infecciones en el paciente oncohematológico / Individualized evaluation of the risk of infections in the oncohematologic patient

En la aproximación al enfermo oncohematológico con fiebre o sospecha de infección es importante conocer no sólo la profundidad y duraciónde la neutropenia, sino también cuál es el estado y la naturaleza de la enfermedad de base del paciente, los tratamientos inmunosupresoresrecibidos y, en su caso, el tipo de trasplante de progenitores hematopoyéticos realizado. Además, es importante considerar susantecedentes personales y familiares en relación con enfermedades infecciosas. Todo en conjunto y en un paciente determinado servirá paracalcular el estado neto de inmunosupresión y el riesgo inherente de infección, para aproximarnos a la etiología más probable y plantearlas estrategias profilácticas y de tratamiento más adecuadas. En este trabajo se exponen cuáles han sido los cambios en las modalidades terapéuticasy los avances en la quimioterapia que nos obligarán, en el futuro, a modificar nuestras pautas de prevención de la infección enel paciente oncohematológico

In order to take the best approach to infection in the oncohematologic patient with fever, it is important to know not only how profoundthe neutropenia is and how long the patient has had it, but also the characteristics of the underlying disease, the immunosuppressive therapyreceived and the type of hematopoietic stem/progenitor cell transplantation performed. Moreover, is important to consider if these patientshave any personal or familial history of infectious diseases. All these aspects let us calculate the net state of immunosuppression andthe risk of infection, and provide us with information about the most probable etiology in each case and the best prophylaxis and treatment.In this study we review the more important advances in chemotherapy in recent years that will make it necessary in the future tochange our prophylactic guidelines for more effective prevention of infection in the oncohematologic patient

Blood and urine samples as useful sources for the direct detection of tuberculosis by polymerase chain reaction.

The aim of the study was to assess the utility of the polymerase chain reaction (PCR) assay in blood and urine for the diagnosis of tuberculosis (TB). We prospectively evaluated the usefulness of PCR performed in blood and urine samples from patients with proved or probable TB compared with a control group of patients. The PCR technique was performed using IS6110 primers. We included in the study 57 patients (43 with definite TB and 14 with probable TB) and 26 controls. Blood and urine samples were drawn at the time of microbiologic diagnosis and 3, 6, 9, and 12 months later. Cultures were positive in the early period (<1 month after treatment) in 11 of 57 patients (19%) with probable or definite TB, in comparison with 42% of patients (24/57) who yielded a positive PCR (P = 0.02). Urine samples increased the sensitivity of PCR determination in blood samples by 10%. The PCR in blood and/or urine was positive in 41% of patients with pulmonary TB, in 36% of patients with extrapulmonary TB, and in 50% of patients with disseminated TB. Mycobacterium tuberculosis was still detectable by PCR in 5 of 13 patients with cured TB after 1 or more months of antituberculous treatment. The PCR detection of M. tuberculosis in blood and urine samples is useful for the diagnosis of different clinical forms of TB, mostly in those patients in which sample extraction is difficult or requires aggressive techniques. The sensitivity of this technique could be improved studying more than 1 sample in each patient, even after initiating an antituberculous treatment.

[Treatment of invasive fungal infections with voriconazole. Evaluation of experience with compassionate use of voriconazole in Spain]. / Tratamiento con voriconazol de las infecciones fungicas invasoras. Evaluacion de la experiencia del uso compasivo de voriconazol en Espana.

Although voriconazole shows an advantageous microbiological and pharmacological profile with respect to amphotericin B and other antifungals, the cumulative experience with the use of voriconazole in patients intolerant to other antifungals or with refractory invasive fungal infections is still limited. We performed a retrospective analysis of the charts of 48 patients in 26 Spanish hospitals who were diagnosed with invasive fungal infections due to filamentous fungi or yeasts and had received voriconazole (between 1999 and 2002) as part of a compassionate use program for a mean of 59.2 days (range 1-748 days). The favorable response rate in patients with invasive, refractory aspergillosis who were treated exclusively with voriconazole was 8/12 (66%). This response rate increased to 10/12 (83%) when two other cases treated with a combination of voriconazole plus caspofungin were included. In patients with invasive candidiasis the response rate was 66% (6/9). A favorable response was achieved in 12/17 (70%) patients with invasive fungal infections due to other difficult to treat fungi (Scedosporium spp., Fusarium spp., Blastoschizomyces spp.). The tolerability and safety profile of voriconazole was good; only four patients required discontinuation of treatment due to side effects. Voriconazole is a well-tolerated, effective antifungal for the treatment of patients with refractory invasive fungal infections due to Aspergillus spp., Candida spp. and fungi resistant or refractory to other treatments.

Gastrostomía percutánea endoscópica complicada con Fascitis necrotizante / Necrotizing fasciitis after percutaneous gastrostomy

La indicación de la gastrostomía endoscópica percutánea es cada día más frecuente debido en parte a la importancia creciente que han adquirido los cuidados paliativos en la actualidad. Debemos conocer las complicaciones que pueden aparecer en estos pacientes. Se presenta un caso de fascitis necrotizante de pared abdominal en un paciente portador de gastrostomía (AU)

Nowadays the necessity of percutaneous gastrostomy is increasing owed to the major importance of palliatives support in several patients. Its necessary to know the complications of this proceeding. We present a patient with abdominal wall necrotizing fasciitis complicating percutaneous endoscopic gastrostomy (AU)

Tratamiento con voriconazol de las infecciones fúngicas invasoras. Evaluación de la experiencia del uso compasivo de voriconazol en España / Treatment of invasive fungal infections with voriconazole. Evaluation of experience with compassionate use of voriconazole in Spain

Aunque el voriconazol ofrece ventajas en cuanto a actividad y características farmacológicas respecto a la amfotericina B y otros antifúngicos,existe todavía una limitada experiencia de su eficacia y seguridad en las infecciones fúngicas invasoras refractarias o resistentes a otrosantifúngicos. Se realizó un análisis retrospectivo de 48 pacientes en 26 hospitales españoles entre 1999 y 2002, que sufrían infecciones invasoraspor hongos filamentosos o por levaduras y que recibieron voriconazol como uso compasivo durante una media de 59,2 días (intervalo1-748 días). La proporción de respuestas favorables en los pacientes con aspergilosis invasora refractaria tratados con voriconazol fue8/12 (66%), o 10/12 (83%) si se añaden dos casos en que se asoció caspofungina. En los pacientes con candidemia y candidiasis invasorala respuesta fue del 66% (6/9). En otras micosis invasoras (Scedosporium spp., Fusarium spp., Blastoschizomyces spp.) se logró una respuestafavorable en 12/17 pacientes (70%). El perfil de tolerabilidad y seguridad de voriconazol fue favorable, suspendiéndose la medicación porefectos secundarios sólo en cuatro casos. Se concluye que el voriconazol es un antifúngico eficaz y bien tolerado para el tratamiento de lasinfecciones invasoras por Aspergillus spp., Candida spp. y hongos emergentes resistentes o refractarias a otros tratamientos

Although voriconazole shows an advantageous microbiological and pharmacological profile with respect to amphotericin B and other antifungals,the cumulative experience with the use of voriconazole in patients intolerant to other antifungals or with refractory invasive fungalinfections is still limited. We performed a retrospective analysis of the charts of 48 patients in 26 Spanish hospitals who were diagnosedwith invasive fungal infections due to filamentous fungi or yeasts and had received voriconazole (between 1999 and 2002) as part of a compassionateuse program for a mean of 59.2 days (range 1-748 days). The favorable response rate in patients with invasive, refractory aspergillosiswho were treated exclusively with voriconazole was 8/12 (66%). This response rate increased to 10/12 (83%) when two other casestreated with a combination of voriconazole plus caspofungin were included. In patients with invasive candidiasis the response rate was66% (6/9). A favorable response was achieved in 12/17 (70%) patients with invasive fungal infections due to other difficult to treat fungi(Scedosporium spp., Fusarium spp., Blastoschizomyces spp.). The tolerability and safety profile of voriconazole was good; only four patientsrequired discontinuation of treatment due to side effects. Voriconazole is a well-tolerated, effective antifungal for the treatment of patientswith refractory invasive fungal infections due to Aspergillus spp., Candida spp. and fungi resistant or refractory to other treatments

[Usefulness of liposomal amphotericin B for the prophylaxis of fungal infection in solid organ transplant recipients]. / Utilidad de la amfotericina B liposomal para la prevención de la infección fúngica en receptores de un trasplante de órgano sólido.

Solid organ transplantation is the best alternative for the treatment of end-stage kidney, liver, heart, pancreas and lung failure. Fungal infections (the most frequent are Candida spp. and Aspergillus spp.) are associated with highest mortality in solid organ transplantation. The systemic use of liposomal amphotericin B has only been studied in liver transplant recipients. The main conclusions that can be drawn from the five studies that have been published are: 1) for the prophylaxis to be effective against Aspergillus spp., a dose of 5 mg/kg/day must be used; 2) its use must be reserved for situations with the highest risk for invasive fungal infections: retransplantation, the need for resurgery and, mainly, for those patients needing haemodialysis. Preliminary studies for the prophylactic use of nebulized liposomal amphotericin B in lung transplant receptors are promising.

Utilidad de la amfotericina B liposomal para la prevención de la infección fúngica en receptores de un trasplante de órgano sólido / Usefulness of liposoma amphotericin B for the prophylaxis of fungal infection in solid organ transplant recipients

El trasplante de órgano sólido es la mejor alternativa para el tratamiento de la insuficiencia en fase terminal de riñón, hígado, corazón, páncreas y pulmón. Las infecciones fúngicas (las más frecuentes por Candida spp. y por Aspergillus spp.) son las que mayor mortalidad producen en los receptores de un trasplante de órgano sólido. El empleo de amfotericina B liposomal por vía sistemática como profilaxis sólo se ha ensayado en receptores de trasplante hepático. Las conclusiones que se pueden extraer de los cinco estudios publicados son: 1) para que la profilaxis sea eficaz frente a Aspergillus spp. se debe administrar a una dosis de 5mg/kg/día; 2) se debe reservar su empleo para las situaciones de alto riesgo de infección fúngica invasora, es decir, retrasplante, necesidad de nueva cirugía tras el trasplante y, principalmente, pacientes que requieren hemodiálisis. Resultan prometedores los estudios preliminares sobre el empleo profiláctico de amfotericina B liposomial administrada por vía nebulizada en receptores de trasplante pulmonar

Solid organ transplantation is the best alternative for the treatment of end-stage kidney, liver, Herat, páncreas and lung failure. Fungal infections (the most frequent are Candida spp. and Aspergillus spp.) are associated with highest mortality in solid organ transplantation. The systemic use of liposomal amphotericin B has only been studied in liver transplant recipients. The main conclusions that can be drawn from the five studies that have been published are: 1) for the prophylaxis to be effective against Aspergillus spp., a dose of 5 mg/kg/day must be used; 2) its use must be reserved for situations with the highest risk for invasive fungal infections: retransplantation, the need of resurgery and, mainly, for those patients needing haemodialysis. Preliminary studies for the prophylactic use of nebulized liposomal amphotericin B in lung transplant receptors are promising

Efficacy and safety of valgancyclovir as preemptive therapy for the prevention of cytomegalovirus disease in solid organ transplant recipients.

We prospectively followed 70 CMV-seropositive solid organ transplant recipients to evaluate the efficacy and safety of valganciclovir (VGCV) as preemptive therapy based on antigenemia test to prevent cytomegalovirus (CMV) disease. From December 2003 to May 2004, 12 of 70 (17%) asymptomatic patients who showed an antigenemia value > or =25 positive cells per 2 x 10(5) polymorphonuclear (PMN) were treated with VGCV (900 mg twice a day adjusted to renal function) until resolution of CMV antigenemia, a minimum of 14 days. No patient developed CMV disease during follow-up. Only one who showed an asymptomatic relapse of the antigenemia test > or =25 positive cells was successfully treated with a repeated course of VGCV. Mean duration of VGCV therapy was 18 days (range, 14 to 28). Antigenemia was negative in 7 of 12 (58%) patients after 14 days and negative in all patients 4 weeks after the administration of VGCV. No significant side effects were associated with the use of VGCV therapy. Preemptive VGCV therapy is safe and effective in the prevention of CMV disease in seropositive solid organ transplant recipients.