Delphi-based study and analysis of key risk factors for invasive fungal infection in haematological patients / Análisis de los factores de riesgo clave para infecciones fúngicas invasoras en pacientes onco-hematológicos: estudio Delphi

Introduction. Mortality caused by invasive fungal infections due to filamentous fungi (IFI-FF) is high. Predisposing factors to IFI-FF are multiple and should be stratified. The objective of this study was to identify key risk factors for IFI-FF in onco-haematological patients in different clinical settings. Methods. Prospective national Delphi study. Risk factors for IFI-FF in patients with onco-haematological diseases were identified by a systematic review of the literature. An anonymous survey was sent by e-mail to a panel of experts. A key risk factor was defined when at least 70% of the surveyed participants assigned a 'maximal' or 'high' risk. Results. In allogenic stem cell transplantation, 18 of the 42 risk factors analyzed were classified as key risk factors, including neutropenia, previous IFI-FF, grade III/IV acute or extensive chronic graft-versus-host disease (GVHD), umbilical cord blood transplantation, HLA mismatching transplantation, graft failure, absence of HEPA filters, absence of laminar air flow, diagnosis of acute myeloid leukaemia, haploidentical transplantation, anti-TNF-α drugs, alemtuzumab, anti-thymocyte globulin, immunosuppressive prophylaxis for GVHD, lymphocytopenia, cytomegalovirus infection, and proximity to construction areas. In acute leukaemia/myelodysplastic syndrome (AL/MDS), 7 of 25 risk factors were defined as key risk factors, including neutropenia, consolidation therapy without response, induction therapy, antifungal prophylaxis with azoles, proximity to construction areas, and absence of HEPA filters. In lymphoma/ multiple myeloma (MM), the five key risk factors among 21 analyzed were use of steroids, neutropenia, progressive disease, anti-CD52 therapies, and proximity to construction areas. Conclusions. The Delphi method was useful for the classification and stratification of risk factors for IFI-FF in patients with onco-haematological diseases. Identifying key risk factors will contribute to a better management of IFI-FF in this group of patients at high or changing risk (AU)

Introducción. La mortalidad por infecciones fúngicas invasoras por hongos filamentosos (IFI-HF) es elevada. Los factores predisponentes de IFI-HF son múltiples y deben ser estratificados. El objetivo de este estudio fue identificar factores de riesgo clave para IFI-HF en pacientes oncohematológicos en diversos contextos clínicos. Métodos. Estudio Delphi, nacional y prospectivo. Mediante revisión sistemática de la literatura se identificaron los factores de riesgo de IFI-HF en pacientes con patología onco-hematológica. Se envió por correo electrónico una encuesta anónima a un panel de expertos. Se definió factor de riesgo clave cuando al menos el 70% de los encuestados le asignaba un riesgo 'máximo' o 'alto'. Resultados. Los factores de riesgo considerados clave fueron: en trasplante alogénico de progenitores hematopoyéticos 18/42 analizados (neutropenia, IFI-HF previa, enfermedad injerto contra huésped aguda III-IV o crónica extensa, trasplante de cordón umbilical, trasplante HLA incompatible, fracaso del injerto, ausencia filtros HEPA, ausencia flujo laminar, diagnóstico de leucemia aguda mieloblástica, trasplante haploidéntico, antiTNF-α, alemtuzumab, globulina antitimocítica, profilaxis inmunosupresora para enfermedad injerto contra huésped, linfocitopenia, citomegalovirus y proximidad a construcciones). En LA/SMD 7/25 (neutropenia, consolidación sin respuesta, IFI-HF previa, inducción, profilaxis con 'azoles', proximidad a construcciones y ausencia filtros HEPA). En linfoma/MM 5/21 analizados (esteroides, neutropenia, enfermedad en progresión, terapias anti-CD52 y proximidad a construcciones). Conclusiones. El método Delphi ha demostrado ser útil para clasificar los factores de riesgo de IFI-HF en pacientes con patología onco-hematológica. La identificación de factores de riesgo clave permitirá adecuar el manejo de IFI-HF en este grupo de pacientes con riesgo alto o cambiante (AU)

[Boosted protease inhibitor monotherapy in HIV-infected patients: results of a study in a real life setting]. / Monoterapia con inhibidores de la proteasa potenciados en pacientes infectados por el VIH: resultados de un estudio en la "vida real".

BACKGROUND: Boosted protease inhibitor monotherapy may offer antiviral efficacy while reducing drug interactions, costs and toxicity. The aim of this study was to assess the efficacy of darunavir/ritonavir (DRV/r) and lopinavir/ritonavir (LPV/r) monotherapy in a real life setting. METHODS: A retrospective analysis of all HIV infected patients, who had initiated DRV/r or LPV/r monotherapy, was performed. Patients whose HIV viral load had remained undetectable for at least two consecutive follow-up visits and who had no neurocognitive disorder or hepatitis B co-infection, were included. RESULTS: Sixty patients were included. The median (IQR) time to follow-up was 66 (33-118) weeks. The proportions (CI95%) of patients with virological failure were 6.3% (1.7- 20.2) and 25.0% (12.7-43.4), respectively, in the DRV/r and LPV/r groups (p= 0.0424). The proportions (CI95%) of patients with therapeutic success were 90.6% (80.5-100) in the DRV/r group and 60.7% (42.6-78.8) in the LPV/r group (p=0.0063). No protease inhibitor mutations were detected. During the follow-up, 6 patients with dyslipidemia normalized their lipid values. The median monthly cost was 410 (IQR 242-416) euros per person lower for the monotherapy than for the combined antiretroviral therapy. CONCLUSIONS: Boosted protease inhibitor monotherapy was effective in a real life setting. This study showed differences in favour of DRV/r as compared with LPV/r in terms of therapeutic success; however prospective studies are needed to confirm these results. Finally, although this study was not specifically designed to detect benefits in terms of costs and lipid profile, it shows evidence of a positive impact of monotherapy in these fields.

Monoterapia con inhibidores de la proteasa potenciados en pacientes infectados por el VIH: resultados de un estudio en la «vida real» / Boosted protease inhibitor monotherapy in HIV-infected patients: results of a study in a real life setting

Introducción. La monoterapia con inhibidores de la proteasa (IP) potenciados (IP/r) podría ofrecer eficacia antiviral, disminuyendo interacciones medicamentosas, toxicidad y costes. El objetivo de este estudio fue determinar la eficacia de la monoterapia con darunavir/ritonavir (DRV/r) y lopinavir/ritonavir (LPV/r) en un escenario de «vida real». Métodos. Se analizaron retrospectivamente todos los pacientes infectados por VIH tratados con DRV/r o LPV/r en monoterapia. Se incluyeron los que antes de iniciar esta estrategia tuvieran carga viral indetectable en dos controles consecutivos, sin trastornos neurocognitivos, ni coinfección con el virus de la hepatitis B. Resultados. Se incluyeron 60 pacientes. La mediana (IQR) de seguimiento fue de 66 semanas (33-118). La proporción de fallos virológicos (IC95%) fue del 6,3% (1,7-20,2) y del 25,0% (12,7-43,4) en pacientes tratados con DRV/r y LPV/r, respectivamente (p= 0,0424). La proporción de éxitos terapéuticos (IC95%) fue del 90,6% (80,5-100) en el grupo de DRV/r y del 60,7% (42,6-78,8) en el de LPV/r (p=0,0063). No se detectaron mutaciones de resistencia a IP. Seis pacientes con dislipemia normalizaron los niveles. La mediana de reducción del coste terapéutico mensual fue de 410 (IQR 242-416) euros/paciente. Conclusión. La monoterapia con IP/r es una estrategia efectiva en pacientes evaluados en un escenario de «vida real». Este estudio demuestra diferencias a favor de DRV/r en términos de éxito terapéutico, aunque estos resultados deben ser confirmados en estudios prospectivos. Si bien este trabajo no fue diseñado para evaluar perfil metabólico ni costes, también se ha observado un impacto positivo de la monoterapia en ambos términos (AU)

Background. Boosted protease inhibitor monotherapy may offer antiviral efficacy while reducing drug interactions, costs and toxicity. The aim of this study was to assess the efficacy of darunavir/ritonavir (DRV/r) and lopinavir/ritonavir (LPV/r) monotherapy in a real life setting. Methods. A retrospective analysis of all HIV infected patients, who had initiated DRV/r or LPV/r monotherapy, was performed. Patients whose HIV viral load had remained undetectable for at least two consecutive follow-up visits and who had no neurocognitive disorder or hepatitis B co-infection, were included. Results. Sixty patients were included. The median (IQR) time to follow-up was 66 (33-118) weeks. The proportions (CI95%) of patients with virological failure were 6.3% (1.7-20.2) and 25.0% (12.7-43.4), respectively, in the DRV/r and LPV/r groups (p= 0.0424). The proportions (CI95%) of patients with therapeutic success were 90.6% (80.5-100) in the DRV/r group and 60.7% (42.6-78.8) in the LPV/r group (p=0.0063). No protease inhibitor mutations were detected. During the follow-up, 6 patients with dyslipidemia normalized their lipid values. The median monthly cost was 410 (IQR 242-416) euros per person lower for the monotherapy than for the combined antiretroviral therapy. Conclusions. Boosted protease inhibitor monotherapy was effective in a real life setting. This study showed differences in favour of DRV/r as compared with LPV/r in terms of therapeutic success; however prospective studies are needed to confirm these results. Finally, although this study was not specifically designed to detect benefits in terms of costs and lipid profile, it shows evidence of a positive impact of monotherapy in these fields (AU)

Does HIV infection have an impact upon dental implant osseointegration? A systematic review

OBJECTIVE: A systematic review is made to determine whether human immunodeficiency virus (HIV) infection has an impact upon dental implant osseointegration. STUDY DESIGN: A PubMed (MEDLINE) literature search was made of articles published up until 14 April 2014. The systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The quality of the studies included in the review was assessed using the Methodological Index for Nonrandomized Studies (MINORS) and levels of evidence (based on the University of Oxford's Center for Evidence Based Medicine criteria). RESULTS: The combinations of search terms resulted in a list of 132 titles. Nine studies finally met the inclusion criteria and were selected for inclusion in the systematic review. A total of 173 dental implants were placed in 80 patients (135 implants in 56 HIV-positive subjects and 38 implants in 24 HIV-negative patients), and a single loss of dental implant osseointegration was recorded in an HIV-positive patient. CONCLUSIONS: Our results suggest that dental implant placement in HIV-positive patients does not increase the dental implant failure rate. Prophylactic antibiotic treatment, the administration of highly active antiretroviral therapy, and control of the CD4+ T lymphocyte counts appear to be the main influencing factors in this respect. Given the few studies included in our systematic review, further prospective studies involving larger sample sizes and longer durations of follow-up are required in order to confirm the results obtained

Dolor crónico y lesión única en metáfisis del radio / Chronic pain and a single lesion in the distal radius

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Does HIV infection have an impact upon dental implant osseointegration? A systematic review.

OBJECTIVE: A systematic review is made to determine whether human immunodeficiency virus (HIV) infection has an impact upon dental implant osseointegration. STUDY DESIGN: A PubMed (MEDLINE) literature search was made of articles published up until 14 April 2014. The systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The quality of the studies included in the review was assessed using the Methodological Index for Nonrandomized Studies (MINORS) and levels of evidence (based on the University of Oxford's Center for Evidence Based Medicine criteria). RESULTS: The combinations of search terms resulted in a list of 132 titles. Nine studies finally met the inclusion criteria and were selected for inclusion in the systematic review. A total of 173 dental implants were placed in 80 patients (135 implants in 56 HIV-positive subjects and 38 implants in 24 HIV-negative patients), and a single loss of dental implant osseointegration was recorded in an HIV-positive patient. CONCLUSIONS: Our results suggest that dental implant placement in HIV-positive patients does not increase the dental implant failure rate. Prophylactic antibiotic treatment, the administration of highly active antiretroviral therapy, and control of the CD4+ T lymphocyte counts appear to be the main influencing factors in this respect. Given the few studies included in our systematic review, further prospective studies involving larger sample sizes and longer durations of follow-up are required in order to confirm the results obtained.

Incidence of hepatocellular carcinoma in hepatitis C cirrhotic patients with and without HIV infection: a cohort study, 1999-2011.

INTRODUCTION. High activity antiretroviral therapy (HAART) has allowed people infected with human immunodeficiency virus (HIV) to live longer. In the course of time, hepatocellular carcinoma (HCC) began to be found in these patients. Investigations have suggested that, as it has been described for other tumors, HIV infection raises the risk of developing HCC. However, convincing evidence is still required. Our aim was to quantify the incidence of HCC in hepatitis C cirrhotic patients with and without human immunodeficiency virus infection in the HAART era. MATERIAL AND METHOds. This prospective cohort study was conducted in hepatitis C cirrhotic patients with and without HIV co-infection, between june 1, 1999 and May 21, 2010. Ultrasound screening for HCC was performed every 6 to 12 months to all the patients until January 15, 2011. Incidence rate and cumulative incidence (Kaplan-Meier) were calculated. RESULTS. One hundred and forty eight patients (69 hepatitis C virus mono-infected and 79 HIV/hepatitis C virus co-infected) were followed for a median time of 43 months, with a total follow-up of 555 person-years (324 for co-infected and 231 for mono-infected patients). Twelve patients developed HCC (5 co-infected and 7 mono-infected). The incidence of HCC in co-infected patients and mono-infected patients was 1.54 (95% confidence interval = 0.5 to 3.6) and 3.03 (95% confidence interval = 1.22 to 6.23) cases per 100 person-year respectively (log-rank p = 0.3225). CONCLUSION. In the HAART era, HIV co-infection is not associated with a higher incidence of HCC in hepatitis C cirrhotic patients.

[Celiac disease in 3 patients with Takayasu's arteritis]. / Enfermedad celíaca en 3 pacientes con arteritis de Takayasu.

Takayasu's arteritis (TA) is a chronic vasculitis of unknown etiology. Celiac disease (CD) is an autoimmune disease caused by the ingestion of gluten. TA and CD have been associated with many other autoimmune conditions. However, only five cases with this association have been reported. In this series, three patients with TA and CD were included; all were female, 21, 30 and 54 years old. TA clinical manifestations preceded CD diagnosis in all patients. Aortic arch branches were affected in all of them. Serologic markers were positive and a small intestine biopsy showed typical findings of CD in the three patients. Special attention should be given to this possible association because these entities may be asymptomatic; the recognition of new disease variants modifies treatment, and sometimes CD constitutes a differential diagnosis of mesenteric ischemia.

[General characteristics of 29 patients with small vessel vasculitis]. / Características generales de 29 pacientes con vasculitis de pequeños vasos.

The objective of this series was to describe the general characteristics and clinical manifestations of patients with small vessel vasculitis who were assisted in the autoimmunity department of a community public hospital and to compare the results with the literature. Clinical records under the label of vasculitis in a period of 16 years were reviewed in a retrospective way. All patients selected fulfilled diagnostic criteria of small vessel vasculitis. The data were extracted and the analysis of survival was completed by phone. Later a bibliographical search was carried out and the results were compared. Thirteen patients with Wegener's granulomatosis, 6 with Churg-Strauss syndrome and 10 with microscopic polyangiitis were included. Fifty five percent (16) were under 55 years old when diagnosis was made and male/female ratio was 2.6 to 1. The diagnostic delay was over a year in 46% of the cases. Respiratory and ear-nose-throat were the most frequently affected systems. Anti-neutrophil cytoplasmic antibodies were present in 79% of patients. Overall mortality was 24% (7/29). There were several differences between the results of our series and the literature: the presentation form, affected systems and percentage of patients with anti-neutrophil cytoplasmic antibodies. Greater diagnostic delay and worse prognosis were observed in anti-neutrophil cytoplasmic antibody negative patients. Special attention should be given to these antibodies since they constitute a significant tool at the time of diagnosis.

Características generales de 29 pacientes con vasculitis de pequeños vasos / General characteristics of 29 patients with small vessel vasculitis

El objetivo de esta serie fue describir las características generales y manifestaciones clínicas de pacientes con vasculitis de pequeños vasos que concurrieron al servicio de autoinmunidad de un hospital de la comunidad y compararlas con la literatura. Se revisaron de manera retrospectiva las historias clínicas archivadas bajo el rótulo de vasculitis en un período de 16 años. Se seleccionaron aquellos pacientes que cumplieran criterios diagnósticos de vasculitis de pequeños vasos. Se extrajeron los datos de interés y se constató la supervivencia mediante contacto telefónico. Posteriormente se realizó una búsqueda bibliográfica y se compararon los resultados. Se incluyeron 13 pacientes con granulomatosis de Wegener, 6 con síndrome de Churg Strauss y 10 con poliangeítis microscópica. El 55% (16) fueron menores de 55 años al diagnóstico y hubo predominio del sexo femenino (2.6:1). La demora diagnóstica fue mayor a un año en el 46% de los casos. Los sistemas más frecuentemente afectados fueron respiratorio y otorrinolaringológico. El 79% presentó anticuerpos anti-citoplasma de neutrófilos (ANCA) positivos. La mortalidad fue del 24% (7/29). Al comparar las características de los pacientes incluidos en esta serie con lo descripto en la literatura, se hallaron diferencias en cuanto a la forma de presentación, sistemas comprometidos y porcentaje de pacientes ANCA positivos; además se observó que el resultado negativo de este marcador parece asociarse con mayor demora diagnóstica y en consecuencia peor pronóstico, lo que remarca su importancia como herramienta adicional no invasiva al momento del diagnóstico.

The objective of this series was to describe the general characteristics and clinical manifestations of patients with small vessel vasculitis who were assisted in the autoimmunity department of a community public hospital and to compare the results with the literature. Clinical records under the label of vasculitis in a period of 16 years were reviewed in a retrospective way. All patients selected fulfilled diagnostic criteria of small vessel vasculitis. The data were extracted and the analysis of survival was completed by phone. Later a bibliographical search was carried out and the results were compared. Thirteen patients with Wegener's granulomatosis, 6 with Churg-Strauss syndrome and 10 with microscopic polyangiitis were included. Fifty five percent (16) were under 55 years old when diagnosis was made and male/female ratio was 2.6 to 1. The diagnostic delay was over a year in 46% of the cases. Respiratory and ear-nose-throat were the most frequently affected systems. Anti-neutrophil cytoplasmic antibodies were present in 79% of patients. Overall mortality was 24% (7/29). There were several differences between the results of our series and the literature: the presentation form, affected systems and percentage of patients with anti-neutrophil cytoplasmic antibodies. Greater diagnostic delay and worse prognosis were observed in anti-neutrophil cytoplasmic antibody negative patients. Special attention should be given to these antibodies since they constitute a significant tool at the time of diagnosis.