Una experiencia de siete años en el laboratorio de Micología del Hospital de Pediatría Juan P. Garrahan / A seven-year experience in the Mycology Laboratory of Hospital de Pediatría Juan P. Garrahan

En noviembre del año 2015 nos incorporamos al Laboratorio de Micología del Servicio de Microbiología del Hospital Garrahan. En este breve resumen queremos compartir los avances logrados a través de nuestra experiencia durante siete años de trabajo profesional. Debido a los diagnósticos realizados y su complejidad, consideramos que el Hospital Garrahan, sus pacientes y la comunidad toda necesitan contar con un laboratorio de Micología que responda a sus necesidades. Creemos haber iniciado un camino que esperamos continúe y culmine con la creación de la Unidad de Micología (AU)

In November 2015 we joined the Mycology Laboratory of the Microbiology Service of the Hospital Garrahan. In this brief summary we want to share the advances achieved through our experience during seven years of professional work. Due to the diagnosis made and their complexity, we believe that the Hospital Garrahan, its patients and the entire community, need to have a Mycology laboratory that responds to their requirements. We believe we have started a path that we hope will continue and culminate with the creation of the Mycology Unit (AU)

Osteomielitis fúngica en niños quemados / Fungal osteomyelitis in burned children

Introducción: En pacientes pediátricos quemados la osteomielitis fúngica es una complicación infrecuente que conduce a una significativa morbilidad. La información en la literatura está limitada a unos escasos reportes de casos. Objetivo: Describir las características clínicas, epidemiológicas y de evolución de niños quemados con osteomielitis fúngica. Métodos: Se llevo a cabo un estudio retrospectivo y descriptivo de pacientes mayores de 1 mes y menores de 18 años quemados con osteomielitis fúngica internados en el hospital Juan P. Garrahan, un hospital terciario en Buenos Aires, Argentina. Resultados: entre enero del 2007 y enero del 2017, de 600 niños quemados, 9 pacientes presentaron diagnóstico confirmado de osteomielitis fúngica. La mediana de edad fue de 42.5 meses (RIC, 27-118 meses) y la mediana de superficie quemada fue de 33.5% (RIC, 18.5-58%). La osteomielitis fue diagnosticada con una mediana de 30 días luego de la quemadura. Las localizaciones más frecuentes de osteomielitis fueron los miembros superiores y a nivel de calota. Los microorganismos aislados a partir del cultivo de hueso fueron: Fusarium spp. en tres pacientes, Mucor spp. en un paciente; Trichosporon asahii en un paciente; Cándida albicans en dos pacientes y Candida parapsilosis en dos pacientes. En dos casos la infección fúngica fue asociada con aislamientos bacteriano concomitante. Todos los pacientes presentaron hallazgos histopatológicos compatibles con osteomielitis. La mediana de tiempo de tratamiento fue de 44.5 días (RIC, 34.5- 65.5 días). Seis pacientes (67%) presentaron secuela motora. Conclusión: La osteomielitis fúngica fue infrecuente Candida spp. y Fusarium spp. fueron los hongos más comúnmente identificados. La secuela funcional fue frecuente (AU)

Introduction: In pediatric burn patients fungal osteomyelitis is a rare complication that leads to significant morbidity. Data in the literature are limited to sporadic case reports. Objective: To describe the clinical and epidemiological features and outcome in burned children with fungal osteomyelitis. Methods: A retrospective descriptive study was conducted in burn patients older than 1 month and younger than 18 years admitted to Hospital Juan P. Garrahan, a tertiary hospital in Buenos Aires, Argentina. Results: Between January 2007 and January 2017, of 600 burned children, nine had a confirmed diagnosis of fungal osteomyelitis. Median age was 42.5 months (IQR, 27-118 months) and median burn surface was 33.5% (IQR, 18.5-58%). Osteomyelitis was diagnosed at a median of 30 days after the burn. The most common location of osteomyelitis were the upper limbs and skull. The microorganisms isolated form bone cultures were Fusarium spp. in three patients, Mucor spp. in one patient; Trichosporon asahii in one patient; Candida albicans in two patients; and Candida parapsilosis in two patients. In two cases the funal infection was associated with concomitant bacterial isolation. In all patients, the histopathological findings were compatible with osteomyelitis. Median duration of treatment was 44.5 days (IQR, 34.5-65.5 days). Six patients (67%) had motor sequelae. Conclusion: Fungal osteomyelitis is a rare disease. Candida spp. and Fusarium spp. were most frequently identified fungi. Functional sequelae were common (AU)

Candidemia en un hospital pediátrico de alta complejidad / Candidemia in a tertiary-care pediatric hospital

Introducción: La frecuencia de las candidemias ha aumentado en los últimos años asociada principalmente a internación prolongada, antibióticos de amplio espectro y enfermedades de base. Se produjo también un cambio en la distribución y un aumento en la resistencia a los antifúngicos de las distintas especies de Candida spp., todo esto asociado a una elevada morbimortalidad. En este trabajo realizado durante un año en un hospital de alta complejidad, se incluyeron 33 pacientes con candidemia. La mediana de la edad fue de 22 meses y un 60% de los afectados fueron varones. El 97% de los niños tenían enfermedad de base con predominio de la patología oncohematológica. Un 88% presentó algún procedimiento o condición predisponente para la infección, principalmente portación de catéter venoso central y cirugía previa. En un 59% de los aislamientos predominaron especies de Candida diferentes de Candida albicans. Anfotericina B desoxicolato fue el tratamiento empírico de elección. La mediana de tratamiento fue de 21 días y la de internación de 66 días. La mortalidad fue del 12% y se asoció a ingreso a UCI, presencia de fiebre al momento del diagnóstico y requerimiento de ARM (AU)

The incidence of candidemia has increased over the past years mainly associated with prolonged hospital stay, wide-spectrum antibiotics, and underlying diseases. At the same time there has been a change in the distribution and an increase in the resistance to antifungals in different Candida spp, associated with a high morbidity and mortality. In this study, conducted during one year at a tertiary hospital, 33 patients with candidemia were included. Median age was 22 months and 60% of the patients were boys. Overall, 97% of the children had an underlying hematology-oncology disease. Of the patients, 88% underwent a procedure or had a condition that predisposed to infection, mainly the placement of a central venous catheter and previous surgery. In 59% the isolated Candida species were Candida albicans. Amphotericin B deoxycholate was the empirical treatment of choice. Median time of treatment was 21 days and median hospital stay was 66 days. Mortality was 12% and was associated with ICU admission, presence of fever at the time of diagnosis, and requirement of mechanical ventilation (AU)

Anidulafungina en niños: Experiencia en niños con trasplante de médula ósea / Anidulafungin in children: experience in children undergoing bone marrow transplantation

Introducción: Las infecciones fúngicas invasoras (IFI) son un problema de salud cada vez mayor, y se asocian con una alta morbilidad y mortalidad. Las nuevas opciones terapéuticas, tales como las equinocandinas y entre estos anidulafungina, se han utilizado en la población adulta, pero en pacientes pediátricos con trasplante de médula ósea la experiencia es escasa. Objetivo: El objetivo de este estudio descriptivo es presentar nuestra experiencia con el uso de la anidulafungina como profilaxis o tratamiento en pacientes con trasplante de médula ósea. Material y métodos: Entre enero hasta junio 2016, 29 pacientes trasplantados de médula ósea recibieron anidulafungina como profilaxis o tratamiento de infecciones fúngicas invasivas (IFI) probadas, probables o posibles. En todos los casos se monitorizó el valor de transaminasas, bilirrubina, creatinina y el recuento de glóbulos blancos al inicio y al final del tratamiento. Resultados: La anidulafungina se administró por vía intravenosa en una dosis de carga de 3 mg/kg/día, seguida de 1,5 mg/kg/día durante una mediana (Md) de 16 días (intervalo intercuartílico: 2-65 d). La Md de la edad de los pacientes fue de 97 meses (rango: 6-211m). La anidulafungina fue indicada como tratamiento en 7 casos (24%) y como profilaxis primaria o secundaria,en 22 (76%). En un paciente se confirmó microbiológicamente una IFI, por Candida albicans. Las Md de los parámetros bioquímicos en el inicio del tratamiento y al final, fueron: transaminasas GOT 29,5 U/l y 32 U/l (p 0,44); bilirrubina 0,35 y 0,30 mg/dL (p: 0,20); creatinina, 0,52 y 0,60 mg/dl (p:0,67). El recuento de glóbulos blancos mostró una gran variabilidad debido a la enfermedad subyacente, pero la diferencia de su valor entre el inicio y al final de la administración del fármaco, no fue significativo: Md 2810 células/mm3 y 5160 células/mm3, respectivamente (p: 0,07). Ninguno de los pacientes tuvo eventos adversos o murieron por causas relacionadas con anidulafungina. En el seguimiento a 30 días no se registró recaída de la infección o mortalidad relacionada a la droga. Conclusiones: Los resultados de nuestra serie sugieren que la anidulafungina podría ser una opción para la profilaxis o el tratamiento de las IFI en los niños con trasplante de médula ósea. Se requieren más estudios para confirmar estas observaciones (AU)

Introduction: Invasive fungal infections (IFI) are an increasing health problem associated with high morbidity and mortality. New treatment options, such as echinocandins and among these anidulafungin, have been used in the adult population, but experience in children undergoing bone marrow transplantation is scarce. Aim: The aim of this descriptive study is to present our experience with the use of anidulafungine as prophylaxis or treatment in patients undergoing bone marrow transplantation. Material and methods: Between January and June 2016, 29 patients who underwent bone marrow transplantation received anidulafungin as prophylaxis against or treatment for confirmed, probable, or possible (IFI). In all cases transaminase, bilirubin, and creatinine levels as well as total white blood cell count were monitored at treatment initiation and completion. Results: Anidulafungine is administered intravenously in a loading dose of 3 mg/kg/day, followed by 1.5 mg/kg/day for a mean of 16 days (interquartile range: 2-65 d). Mean age of the patients was 97 months (range: 6-211m). Anidulafungine was used as treatment in 7 cases (24%) and as primary or secondary prophylaxis in 22 (76%). IFI was microbiologically confirmed to be Candida albicans in one patient. Mean biochemical parameters at treatment onset and completion were: transaminases AST 29.5 U/l and 32 U/l (p 0.44); bilirubin 0.35 and 0.30 mg/dL (p 0.20); creatinine, 0.52 and 0.60 mg/dl (p : 0.67). White blood cell count was highly variable due to the underlying disease; however, the difference between values at treatment initiation and completion were not significant: Mean 2810 cells/mm3 and 5160 cells/mm3, respectively (p: 0.07). None of the patients had adverse effects or died because of anidulafungin-related causes. At 30 days of follow-up no relapse of infection or drug-related mortality was observed. Conclusions: The results in our series suggest that anidulafungin is an option for the prophylaxis against or treatment of IFI in children undergoing bone marrow transplantation. Further studies are necessary to confirm these findings (AU)

Mild cognitive impairment: a concept in evolution.

The construct of mild cognitive impairment (MCI) has evolved over the past 10 years since the publication of the new MCI definition at the Key Symposium in 2003, but the core criteria have remained unchanged. The construct has been extensively used worldwide, both in clinical and in research settings, to define the grey area between intact cognitive functioning and clinical dementia. A rich set of data regarding occurrence, risk factors and progression of MCI has been generated. Discrepancies between studies can be mostly explained by differences in the operationalization of the criteria, differences in the setting where the criteria have been applied, selection of subjects and length of follow-up in longitudinal studies. Major controversial issues that remain to be further explored are algorithmic versus clinical classification, reliability of clinical judgment, temporal changes in cognitive performances and predictivity of putative biomarkers. Some suggestions to further develop the MCI construct include the tailoring of the clinical criteria to specific populations and to specific contexts. The addition of biomarkers to the clinical phenotypes is promising but requires deeper investigation. Translation of findings from the specialty clinic to the population setting, although challenging, will enhance uniformity of outcomes. More longitudinal population-based studies on cognitive ageing and MCI need to be performed to clarify all these issues.

The symptom of low mood in the prodromal stage of mild cognitive impairment and dementia: a cohort study of a community dwelling elderly population.

OBJECTIVE: To investigate the symptom of low mood as a predictor of mild cognitive impairment (MCI) and its progression to dementia, taking into account: (i) MCI severity, (ii) time of assessment and (iii) interaction with other factors. METHODS: 764 cognitively healthy elderly subjects living in the community, from the Kungsholmen Project. Participants were assessed by direct interview to detect low mood. Subjects were then followed for 6 years to identify those who developed MCI. People with incident MCI were followed for a further 3 years to assess progression to dementia. RESULTS: People with low mood at baseline had a 2.7-fold (95% CI 1.9 to 3.7) increased risk of developing MCI at follow-up. The association was stronger for amnestic MCI (aMCI: HR 5.8; 95% CI 3.1 to 10.9) compared with global cognitive impairment (other cognitive impairment no dementia, oCIND: HR 2.2; 95% CI 1.5 to 3.3). ApoE-ε4 interacted with low mood in a synergistic fashion, increasing the risk of aMCI, while no interaction with psychiatric, vascular, frailty related or psychosocial factors was observed. Low mood at baseline, as opposed to low mood co-occurring with MCI, was associated with a 5.3-fold (95% CI 1.2 to 23.3) increased risk of progression to dementia in aMCI. In contrast, no association was found in oCIND. CONCLUSION: Low mood was more strongly associated with aMCI than with global cognitive impairment. Progression towards dementia was predicted only by low mood manifest in the prodromal stage of MCI. These findings indicate that low mood is particularly prominent in the very early stages of cognitive decline.

Epidemiological studies of cognitive impairment and dementia across Eastern and Middle European countries (epidemiology of dementia in Eastern and Middle European Countries).

OBJECTIVE: To determine the availability and the consistency of prevalence findings of epidemiological studies on cognitive impairment and dementia conducted in Eastern and Middle Europe. METHODS: We adopted a stepwise multimethod study approach consisting of iterative literature searches for epidemiological articles published between 1990 and 2006 and subsequent data analyses of published material, reanalyses of existing accessible epidemiological data sets and expert inquiries in Eastern and Middle European countries. Systematic computer-assisted searches used the keywords: "dementia", "Alzheimer", "cognitive impairment", "incidence", "prevalence", "epidemiology" in combination with the name of the relevant countries or "Europe" in English and Polish language. We supplemented the literature search with a review of the references in the articles that were identified during the initial search. RESULTS: We were able to find few regional and country-specific epidemiological studies of various kinds (population-based, cohort, cross-sectional studies) and conducted on different restricted population groups of patients (from neurological units, out-patients units, residential homes). No studies were identified from most of the countries taken under consideration and the ones we found were characterized by an immense diversity with a considerable degree of clinical and methodological variations. The few studies that there are suggest prevalence rates of dementia in Eastern Europe similar to those in Western Europe. CONCLUSIONS: There is strong need for epidemiological studies in Eastern and Middle Europe, as well as for greater coordination and standardization of methods to improve the quality and comparability of epidemiological data to determine the prevalences' rates of dementia in all the EU countries.

Occurrence of cognitive impairment and dementia in the community: a 9-year-long prospective study.

OBJECTIVE: To determine incidence rates of non-dementia cognitive impairment, to examine the impact of attrition due to death on the observed incidence estimates, and to compare the observed and corrected estimates of non-dementia cognitive impairment with dementia incidence rates. METHODS: A total of 1,435 persons without dementia aged 75+ from the Kungsholmen Project were evaluated for occurrence of dementia over 9 years. A total of 1,070 cognitively unimpaired subjects were also followed using amnestic mild cognitive impairment (aMCI) and other cognitive impairment, no dementia (OCIND) definitions. To correct the observed incidence rates for attrition due to death, cognitive status for subjects lost due to death was imputed using information on previous cognitive and health status. Observed and corrected incidence rates (IR) and 95% CIs were calculated with the person-years method, using Poisson distribution. RESULTS: Incidence rates per 1,000 person-years were as follows: dementia IR = 70.4 (64.0 to 77.4); aMCI observed IR = 11.4 (8.6 to 15.1), corrected IR = 13.7 (10.3 to 18.2); OCIND observed IR = 33.8 (28.7 to 39.8), corrected IR = 42.1 (36.5 to 48.6). Both aMCI and OCIND incidence increased with advancing age. Observed incidence of aMCI and OCIND together was similar to that of dementia at age 75 to 79 but lower at more advanced ages. However, the cognitive impairment incidence after age 79 increased substantially when the estimates were corrected for attrition due to death during follow-up. CONCLUSIONS: Non-dementia cognitive impairment is common and often underestimated in population studies that do not adjust for attrition.

Determinants of the subjective functional outcome of total joint arthroplasty.

The aim of the study is three-fold: (i) to analyze association between early subjective functional outcome of total joint arthroplasty (TJA) and patient-related risk factors; (ii) to evaluate the six-month subjective functional outcome of TJA as compared with subjective functional status of non-operated outpatients; (iii) to evaluate TJA self-perceived amelioration rates compared to the status of an age-matched sample from a general medical practice. A prospective consecutive study was performed upon 100 elderly inpatients with recent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) for osteoarthritis. Interviews on preoperative status and short-term outcome were performed at admission and six months after surgical intervention with Western Ontario and MacMasters Universities Osteoarthritis Index (WOMAC). One hundred aged-matched consecutive outpatients were screened for osteoarthritis and interviewed with the same questionnaire in a single session. Differences between baseline and follow-up scores were evident and statistically significant for both TJA groups, although THA patients showed more improvement. The comparison between TJA patients at baseline and age-matched osteoarthritis outpatients highlighted less impairment among outpatients. The situation reversed six months after the intervention. Objective functional outcome of post-operative rehabilitation has not revealed predictive value for the six-month outcome of TJA in terms of self-perceived functional status. Logistic regression analysis indicated that preoperative status was the only significant predictor of higher WOMAC scores six months after TJA. The survey confirms the early benefit of THA or TKA for osteoarthritis, but a less favorable subjective functional outcome is expected at six months when preoperative subjective functional status is severely compromised.

Self-perceived distress and self-perceived functional recovery after recent total hip and knee arthroplasty.

The research was aimed at verifying whether psychological distress and depression are associated to reduced functional improvement following arthroplasty. Thirty-six patients with total knee arthroplasty (TKA) and 36 patients total hip arthroplasty (THA) were enrolled at the beginning of their rehabilitation. The mean age in TKA patients was 71.3+/-7.8 years (S.D.). The mean age in THA patients was 67.9+/-8.4 years. The Western Ontario and MacMasters Universities Osteoarthritis Index (WOMAC) and the Hospital Anxiety and Depression (HAD) were applied. Forty-four percent of THA and 58% of TKA showed over-threshold HAD scores at admission. The proportion was even higher considering HAD-Depression sub-scale, where 55% of THA and 61% of TKA patients had over-threshold scores. Lack of depression prompted better functional outcome in TKA. The effect of depression on TKA functional improvement was still significant after adjusting for age and sex. No association was found for THA patients. In order to maximize rehabilitation benefit it is then suggested that patients with recent TKA intervention are screened for distress and depression at admission and that psychological symptoms are treated if over-threshold.

Cardiac effects of slow-release lanreotide, a slow-release somatostatin analog, in acromegalic patients.

Cardiac involvement, mostly characterized by left ventricular hypertrophy associated with various degrees of cardiac dysfunction, greatly contributes to the increased mortality and morbidity observed in acromegaly. Lanreotide is a new SRIF analog characterized by a slow-release (SR) formulation with the peculiarity of a 30-mg im administration every 10-14 days. In this study, 13 patients with postoperative active acromegaly (9 females, 4 males, 45.9 +/- 16.3 yr old) underwent an echo-Doppler and hormonal study before and during a 12-month period of treatment with SR-lanreotide. GH and insulin-like growth factor I plasma levels (mean +/- SD) decreased significantly throughout the study period (from 10.1 +/- 2.2 to 3.9 +/- 0.9 ng/mL for GH, P < 0.005; and from 511.0 +/- 33.0 to 305.0 +/- 34.2 ng/mL for insulin-like growth factor I, P < 0.0001). Left ventricular mass index (mean +/- SD, 137.1 +/- 7.5 g/m2 at baseline) decreased after 3 months (120.0 +/- 5.4 g/m2), 6 months (111.7 +/- 5.7 g/m2), and 12 months (110.3 +/- 5.2 g/m2) of treatment (P < 0.005 at each time-point). This reduction in left ventricular mass index was accompanied by an improvement in some indexes of left ventricular diastolic function, especially the isovolumetric relaxation time (mean +/- SD, 109.1 +/- 4.6 m/sec at baseline), which decreased after 3 months (91.9 +/- 2.8 m/sec), 6 months (92.3 +/- 3.2 m/sec), and 12 months (92.2 +/- 3.0 m/sec) of treatment (P < 0.005 at each time-point). We conclude that SR-lanreotide is able to improve cardiac morphology and functional abnormalities in acromegaly; whether such beneficial effects on cardiac parameters will contribute to improve life expectancy in these patients should be further investigated.

Acute effects of octreotide, cabergoline and a combination of both drugs on GH secretion in acromegalic patients.

PURPOSE: The acute GH lowering effects of a single dose of either octreotide (OCT) or cabergoline (CAB), given alone and in combination, were studied in a series of 21 patients with acromegaly. PATIENTS AND METHODS: Plasma GH was measured for 8 hours after a single subcutaneous injection of OCT (100 micrograms) and for 48 hours after a single oral dose of CAB (0.5 mg) in all patients. Fourteen patients, who did not suppress GH levels below 5 micrograms/L after either OCT or CAB given alone, also received a combination of both drugs (OCT 100 micrograms s.c. + CAB 0.5 mg p.o. 24 h before OCT). RESULTS: GH levels were acutely suppressed by more than 50% in 15/21 cases after OCT alone and in 5/21 after CAB alone, respectively (P < 0.01). In the 14 patients who received the combined test, the magnitude of GH suppression was significantly higher than after OCT alone 4, 6 and 8 hours after OCT administration (P < 0.02). In patients with mixed GH/PRL-secreting tumors, the additive effect of OCT and CAB was observed at each time point. CONCLUSION: These results suggest that combined therapy with OCT and CAB may be more effective in suppressing GH secretion than either compound given alone, especially in patients with GH/PRL-secreting adenomas.