Outbreak of Pseudomonas aeruginosa infections after CT-guided spinal injections.

BACKGROUND: Meningitis and spinal infections with Gram-negative bacteria after local injections for treatment of chronic back pain are rare. This study investigated an outbreak of Pseudomonas aeruginosa infections following computed tomography (CT)-guided spinal injections (SI). METHODS: A case was defined as a spinal infection or meningitis with P. aeruginosa after SI between 10th January and 1st March 2019 in the same outpatient clinic. Patients without microbiological evidence of P. aeruginosa but with a favourable response to antimicrobial therapy active against P. aeruginosa were defined as probable cases. FINDINGS: Twenty-eight of 297 patients receiving CT-guided SI during the study period developed meningitis or spinal infections. Medical records were available for 19 patients. In 15 patients, there was microbiological evidence of P. aeruginosa, and four patients were defined as probable cases. Two of 19 patients developed meningitis, while the remaining 17 patients developed spinal infections. The median time from SI to hospital admission was 8 days (interquartile range 2-23 days). Patients mainly presented with back pain (N=18; 95%), and rarely developed fever (N=3; 16%). Most patients required surgery (N=16; 84%). Seven patients (37%) relapsed and one patient died. Although the source of infection was not identified microbiologically, documented failures in asepsis when performing SI probably contributed to these infections. CONCLUSIONS: SI is generally considered safe, but non-adherence to asepsis can lead to deleterious effects. Spinal infections caused by P. aeruginosa are difficult to treat and have a high relapse rate.

Vertebral osteomyelitis in patients with Staphylococcus aureus bloodstream infection: Evaluation of risk factors for treatment failure.

OBJECTIVES: Staphylococcus aureus is the most common cause of pyogenic vertebral osteomyelitis (VO). Studies indicate that S. aureus VO results in poor outcome. We aimed to investigate risk factors for treatment failure in patients with Staphylococcus aureus bloodstream infection (SAB) and VO. METHODS: We conducted a post hoc-analysis of data from a German bi-center prospective SAB cohort (2006-2014). Patients were followed-up for one year. Primary outcome was treatment failure defined as relapse and/or death within one year. RESULTS: A total of 1069 patients with SAB were analyzed, with 92 VO patients. In addition to antibiotic treatment, surgery was performed in 60/92 patients. Treatment failed in 44/92 patients (death, n = 42; relapse, n = 2). Multivariable analysis revealed higher age (HR 1.04 [per year], 95%CI 1.01-1.07), Charlson comorbidity index (HR 1.20, 95%CI 1.06-1.36), presence of neurologic deficits (HR 2.53, 95%CI 1.15-5.53) and local abscess formation (HR 3.35, 95%CI 1.39-8.04) as independent risk factors for treatment failure. In contrast, surgery seemed to be associated with a favourable outcome (HR 0.45 (95%CI 0.20-0.997)). CONCLUSION: SAB patients with VO exhibit a high treatment failure rate. Red flags are older age, comorbidities, neurologic deficits and local abscess formation. Whether these patients benefit from intensified treatment (e.g. radical surgery, prolongation of antibiotics) should be investigated further.

Automated Detection and Segmentation of Brain Metastases in Malignant Melanoma: Evaluation of a Dedicated Deep Learning Model.

BACKGROUND AND PURPOSE: Malignant melanoma is an aggressive skin cancer in which brain metastases are common. Our aim was to establish and evaluate a deep learning model for fully automated detection and segmentation of brain metastases in patients with malignant melanoma using clinical routine MR imaging. MATERIALS AND METHODS: Sixty-nine patients with melanoma with a total of 135 brain metastases at initial diagnosis and available multiparametric MR imaging datasets (T1-/T2-weighted, T1-weighted gadolinium contrast-enhanced, FLAIR) were included. A previously established deep learning model architecture (3D convolutional neural network; DeepMedic) simultaneously operating on the aforementioned MR images was trained on a cohort of 55 patients with 103 metastases using 5-fold cross-validation. The efficacy of the deep learning model was evaluated using an independent test set consisting of 14 patients with 32 metastases. Manual segmentations of metastases in a voxelwise manner (T1-weighted gadolinium contrast-enhanced imaging) performed by 2 radiologists in consensus served as the ground truth. RESULTS: After training, the deep learning model detected 28 of 32 brain metastases (mean volume, 1.0 [SD, 2.4] cm3) in the test cohort correctly (sensitivity of 88%), while false-positive findings of 0.71 per scan were observed. Compared with the ground truth, automated segmentations achieved a median Dice similarity coefficient of 0.75. CONCLUSIONS: Deep learning-based automated detection and segmentation of brain metastases in malignant melanoma yields high detection and segmentation accuracy with false-positive findings of <1 per scan.

[Brain metastases-Interdisciplinary approach towards a personalized treatment]. / Hirnmetastasen ­ interdisziplinär zu einer personalisierten Behandlung.

The incidence, treatment and prognosis of patients with brain metastases have substantially changed during the last decades. While the survival time after diagnosis of cerebral metastases was on average a maximum of 3-6 months only 10 years ago, the survival time could be significantly improved due to novel surgical, radiotherapeutic and systemic treatment modalities. Only a few years ago, the occurrence of brain metastases led to a withdrawal from systemic oncological treatment and the exclusion of drug therapy studies and to a purely palliatively oriented treatment in the sense of whole brain radiation therapy (WBRT) with or without surgery. The increasing availability of targeted and immunomodulatory drugs as well as adapted radio-oncological procedures enable increasingly more personalized treatment approaches. The aim of this review article is to demonstrate the progress and complexity of the treatment of brain metastases in the context of modern comprehensive interdisciplinary concepts.

SEOM clinical guideline for secondary prevention (2019).

Cancer is one of the major public health problems in our society. It is estimated that more than 18 million new cases are diagnosed worldwide every year; 280,000 in Spain. Incidence in following a growing trend. This epidemic could be controlled with research into new treatments and, above all, with adequate prevention. Primary prevention could prevent avoid up to half of all cases. For many others, secondary prevention is essential, as it make diagnosis possible in the stages of the disease when it is easily curable. These guidelines present the scientific evidence regarding secondary prevention in tumors in which its use is well-accepted: breast, cervical, colorectal, prostate, lung, ovarian, melanoma, and gastric cancer.

[Importance of interdisciplinary collaboration for optimal treatment of orbital tumors]. / Bedeutung der interdisziplinären Zusammenarbeit für eine optimale Behandlung orbitaler Tumoren.

Optimal treatment of tumors with orbital invasion may exceed the competences of an individual medical specialty and require interdisciplinary cooperation. The aim of this article is to present an interdisciplinary treatment concept based on the examples of intraorbital hemangioma and squamous cell carcinoma of the paranasal sinuses infiltrating the orbit. In addition to a detailed medical history and a complete ophthalmological examination, a detailed imaging technique with standardized echography and tomography methods such as orbital thin-slice CT and/or in many cases MRI is essential for the primary classification of an intraorbital pathology. Depending on the type of pathology, a purely surgical procedure involving various disciplines such as ophthalmology, otorhinolaryngology, maxillofacial surgery, neurosurgery, and pathology, or an interdisciplinary treatment regimen including (neo)adjuvant radiotherapy or chemotherapy is necessary. Orbital tumors have a wide range of potential pathologies, requiring complex surgical procedures and multimodal therapies. In case of infiltration of the paranasal sinuses or intracranial structures, an interdisciplinary team including neuroradiologists, oral-maxillofacial surgeons, otorhinolaryngologists, neurosurgeons, radiation therapists, ophthalmologists, pathologists, oncologists, and psycho-oncologists is essential for successful treatment.

Infectious postoperative endophthalmitis after cataract surgery performed over 7 years. The role of azithromycin versus ciprofloxacin eye drops.

OBJECTIVE: Although topical antibiotics have been used as antimicrobial prophylaxis after ocular surgery, recent studies have determined that intracameral cefuroxime at the end of surgery significantly reduce the risk to suffer an infection and suggest that the use of topical antibiotics in the prophylaxis of infectious postoperative endophthalmitis (IPOE) is controversial. Moreover, there is no evidence to confirm the higher effectiveness of topical ciprofloxacin, considered the standard of care, or topical azithromycin in preventing IPOE of cataract surgeries. METHODS: IPOE topical prophylaxis was performed with two different strategies: with azithromycin from January 1st, 2010 to December 31st, 2014 (group I) and with ciprofloxacin from January 1st, 2015 to January 31st, 2017 (group II). Patient characteristics and clinical signs and symptoms of IPOE from all consecutive cataract surgeries performed over a 7-year period were collected. RESULTS: A total of 15,146 cataract surgeries were conducted; 10,756 in group I and 4,390 in group II. Two cases of IPOE in each group were diagnosed, showing a 0.019% and 0.046% rate respectively, with no statistically significance. IPOE cases were related with aging, systemic and ocular comorbidities or with a complicated cataract surgery. CONCLUSIONS: The benefit of the application of topical antibiotics after cataract surgery is questionable when intracameral cefuroxime prophylaxis is performed and no better effectiveness with ciprofloxacin or azithromycin was observed.

An antimicrobial stewardship program reduces antimicrobial therapy duration and hospital stay in surgical wards.

We report a quasi-experimental study of the implementation of an antimicrobial stewardship program in two surgical wards, with a pre-intervention period with just assessment of prescription and an intervention period with a prospective audit on antibiotic prescription model. There was a significant reduction of length of stay and the total days of antimicrobial administration. There were no differences in mortality between groups. The antimicrobial stewardship program led to the early detection of inappropriate empirical antibiotic treatment and was associated with a significant reduction in length of stay and the total duration of antimicrobial therapy.

Enterococcal bloodstream infection. Design and validation of a mortality prediction rule.

BACKGROUND: To develop a prediction rule to describe the risk of death as a result of enterococcal bloodstream infection. METHODS: A prediction rule was developed by analysing data collected from 122 patients diagnosed with enterococcal BSI admitted to the Clínica Universidad de Navarra (Pamplona, Spain); and validated by confirming its accuracy with the data of an external population (Hospital del Mar, Barcelona). RESULTS: According to this model, independent significant predictors for the risk of death were being diabetic, have received appropriate treatment, severe prognosis of the underlying diseases, have renal failure, received solid organ transplant, malignancy, source of the bloodstream infection and be immunosuppressed. The prediction rule showed a very good calibration (Hosmer-Lemeshow statistic, P = 0.93) and discrimination for both training and testing sets (area under ROC curve = 0.84 and 0.83 respectively). CONCLUSIONS: The predictive rule was able to predict risk of death as a result of enterococcal bloodstream infection as well as to identify patients, who being below the threshold value, will have a low risk of death with a negative predictive value of 96%.

Degree of adherence to recommended antiviral treatment during the pandemic and post-pandemic periods of influenza A(H1N1)pdm09 in 148 intensive care units in Spain.

OBJECTIVE: To determine the degree of antiviral treatment recommendations adherence and its impact to critical ill patients affected by influenza A(H1N1)pdm09 mortality. DESIGN: Secondary analysis of prospective study. SETTING: Intensive care (UCI). PATIENTS: Patients with influenza A(H1N1)pdm09 in the 2009 pandemic and 2010-11 post-Pandemic periods. VARIABLES: Adherence to recommendations was classified as: Total (AT); partial in doses (PD); partial in time (PT), and non-adherence (NA). Viral pneumonia, obesity and mechanical ventilation were considered severity criteria for the administration of high antiviral dose. The analysis was performed using t-test or «chi¼ square. Survival analysis was performed and adjusted by Cox regression analysis. RESULTS: A total of 1,058 patients, 661 (62.5%) included in the pandemic and 397 (37.5%) in post-pandemic period respectively. Global adherence was achieved in 41.6% (43.9% and 38.0%; P=.07 respectively). Severity criteria were similar in both periods (68.5% vs. 62.8%; P=.06). The AT was 54.7% in pandemic and 36.4% in post-pandemic period respectively (P<.01). The NA (19.7% vs. 11.3%; P<.05) and PT (20.8% vs. 9.9%, P<.01) was more frequent in the post-pandemic period. The mortality rate was higher in the post-pandemic period (30% vs. 21.8%, P<.001). APACHE II (HR=1.09) and hematologic disease (HR=2.2) were associated with a higher mortality and adherence (HR=0.47) was a protective factor. CONCLUSIONS: A low degree of adherence to the antiviral treatment was observed in both periods. Adherence to antiviral treatment recommendations was associated with lower mortality rates and should be recommended in critically ill patients with suspected influenza A(H1N1)pdm09.

Neumonía por pneumocystis jiroveci: características clínicas y factores de riesgo asociados a mortalidad en una unidad de cuidados intensivos / Pneumocystis jiroveci pneumonia: clinical characteristics and mortality risk factorsinanintensive care unit

Objetivo. Describir las características epidemiológicas de la población con neumonía por Pneumocystis jiroveci (P. jiroveci), analizando factores de riesgo asociados a la enfermedad, factores predisponentes para ingreso en una unidad de cuidados intensivos (UCI) y factores pronóstico de mortalidad. Diseño y pacientes Estudio observacional y retrospectivo de una cohorte de pacientes ingresados consecutivamente en un hospital de España desde el 1 de enero del 2007 al 31 de diciembre del 2011 cuyo diagnóstico final fue neumonía por P. jiroveci.ÁmbitoUCI y servicio de hospitalización del Hospital del Mar, Barcelona. Resultados. Se incluyeron 36 pacientes con neumonía por P. jiroveci de los que 16 (44,4%) precisaron de ingreso en UCI. La edad media de todos los pacientes fue de 41,3±12 años, de los que 23 (63,9%) eran hombres. El 86,1% tenía antecedente de infección por virus de la inmunodeficiencia humana (VIH) y el resto (el 13,9%) de alguna enfermedad inmunológica con tratamiento inmunosupresor. Los factores de riesgo asociados a mortalidad hospitalaria fueron la edad (51,8 vs. 37,3 años; p=0,002), APACHE mayor al ingreso (17 vs. 13 puntos; p=0,009), la necesidad de ventilación mecánica invasiva (27,8 vs. 11,1%; p=0,000), requerimiento de fármacos vasoactivos (25 vs. 11,1%; p=0,000), coinfección fúngica (22,2 vs. 11,1%; p=0,001), neumotórax (16,7 vs. 83,3%; p=0,000) ingreso en UCI (27,8 vs. 72,2%; p=0,000). Conclusiones. Los altos requerimientos de ventilación mecánica y de fármacos vasoactivos asociado a la coinfección fúngica y presencia de neumotórax en pacientes ingresados en la UCI continúan siendo factores de riesgo asociados a mayor mortalidad en pacientes con neumonía por P. jiroveci.

Computer-based quantification of the Achilles tendon thickness in sequential B-mode ultrasound images: a study of feasibility and reliability.

INTRODUCTION: Assessment of the Achilles tendon thickness (ATT) using B-mode ultrasound is a common technique for clinical evaluation of chronic mid-part tendinosis. Currently used image-based assessment is limited by relatively high inter- and intra-observer variability. In this study, it was tested whether a new sequence-based automated assessment of ATT provides more reliable and reproducible results than the standard image-based procedure. MATERIALS AND METHODS: A total of 118 non-operated tendons of 59 healthy subjects (44, range 28-50 years) were analysed using an automated image based as well as a newly developed automated sequence-based method. Correlation and agreement of both methods were evaluated. The root mean square deviation (RMSD) and a Bland-Altman analysis were performed to highlight observer (n = 18 tendons) as well as reader (n = 40 tendons) dependent variabilities of both methods. RESULTS: A strong correlation was found between image and sequence-based ATT assessment (p = 0.92). The Bland-Altman analysis showed a good agreement between both methods (mean difference 0.0018, 95 % CI: -0.046; 0.05). In repetitive examinations, sequence-based analysis showed a significant reduction concerning reader- and observer-dependent variability compared to image-based assessment. The RMSD for repetitive sequence-based measurements was approximately 0.3 mm (compared to 0.6 mm for image-based measurement), respectively. CONCLUSIONS: The study shows sequence-based automated assessment of ATT being clearly superior to the standard image-based procedure. The new method provides a clear reduction of reader as well as observer-dependent variability. Due to the decreased scattering of measurement data sequence-based measurement seems especially valuable for quantification of small tendon thickness changes such as exercise-induced hypertrophy.

Effects of high altitude on morphophysiological patterns, perception and attention capacity in students from Putre (3500 m. a. s. l. ) and Arica (2 m. a. s. l. ), Chile / Efectos de la altura sobre patrones morfofisiológicos y en la capacidad atencional y de percepción en estudiantes de las comunas de Putre (3500 msnm) y de Arica (2 msnm), Chile

High altitude hypoxia is a stress that triggers several adaptive mechanisms, one of which is how the brain responds to lack of oxygen. The aim of this study was to determine changes in morphological and physiological patterns and in the attention capacity and perception in student populations from the highlands and from a sea level location. Eighty students, aged 14 to 16 years old, both sexes, from the Municipalities of Putre (3500 m.a.s.l.) and Arica (2 m.a.s.l.) participated in this study, with each group composed of 20 women and 20 men. After informed consent was obtained and with the students acceptance, parameters such as weight, height, BMI, heart rate, systolic and diastolic blood pressures were obtained. Subsequently, a psychometric test of attention and perception was applied. The results determined that the population from Putre had less weight and height than students from Arica. Males exhibited a significant decrease in heart rate and women had lower systolic and diastolic blood pressures than in the assessed sea level population. The levels of response in the psycho-technical tests were significantly lower in the population from high altitude, both in males and females. We conclude that high altitude causes changes in morphological and physiological patterns and in responsiveness in psycho-technical tests. However, further studies in psycho-perception are required to delineate the effects that are unique of ethnicity, culture and worldview of the people living in high altitude and their levels of response.

La hipoxia de altura es un estrés que dispara varios mecanismos adaptativos, uno de ellos es como el cerebro responde frente a la falta de oxígeno. El objetivo de este trabajo fue determinar cambios en los patrones morfológicos, fisiológicos y en la capacidad de atención y precepción de población estudiantil que vive en altura y a nivel del mar. Ochenta estudiantes de entre 14 a 16 años de ambos sexos, pertenecientes a las Comunas de Putre (3500 msnm) y Arica (2 msnm) participaron de este estudio. Cada grupo con 20 mujeres y 20 hombres fue medido para determinar su peso, talla, IMC, frecuencia cardiaca, presión sistólica y diastólica. Posteriormente se les aplicó una prueba psicométrica de atención y percepción. Los resultados determinan que la población de Putre presenta menor peso y talla que los alumnos de Arica. Los hombres muestran una disminución significativa de la frecuencia cardiaca y las mujeres presentan una presión sistólica y diastólica menor que lo observado en la población a nivel del mar. Los niveles de respuesta en la prueba psicotécnica son significativamente más bajos en la población que vive en altura tanto en hombres como mujeres. Se concluye que la altura provoca cambios en los patrones morfológicos, fisiológicos y en la capacidad de respuesta en el test psicotécnico. Sin embargo se requieren de mayores estudios de psicopercepción que permitan delimitar los efectos que son propios de la etnia, cultura y la cosmovisión de los pueblos que viven en altura y los niveles de respuesta de esta población.

Intra- and inter-species spread of carbapenemase genes in a non-hospitalized patient.

The purpose of this study was to report intra- and inter-species spread of carbapenemase genes between gram negative rods isolated from a non-hospitalized patient with bacteremia. The approach included chart review, antibiotic susceptibility testing and phenotypic screening for metallo-ß-lactamase (MBL) detection, PCR and sequencing of bla, aac(6')-Ib and qnr genes, and plasmid analysis by PCR-based replicon typing. The clonal relationships between the isolates were analysed by comparing PFGE profiles. A non-hospitalized patient presented bacteraemia due to wild type Enterobacter cloacae (4.08), a VIM-1-producing E. cloacae (5.08), a VIM-1- and CTX-M-9-producing E. cloacae (7.08), a VIM-2-producing Pseudomonas aeruginosa, and catheter colonization by VIM-1-producing Klebsiella oxytoca. The patient had no previous hospitalization but had recently undergone an ambulatory colonoscopy. In E. cloacae 7.08 and K. oxytoca isolates, the bla(VIM-1) gene was located on a transferable plasmid of 48.5 kb, while in E. cloacae 5.08 the bla(VIM-1) gene was encoded on a 194 kb non-transferable plasmid. The bla(CTX-M-9) gene detected in E. cloacae was encoded on an HI2 plasmid of 290 kb. To date the prevalence of VIM-1 enzymes in the community is low. This molecular finding suggests an intra-species and/or inter-species horizontal spread of the MBL gene in the same non-hospitalized patient.

Bevacizumab can induce reactivity to VEGF-C and -D in human brain and tumour derived endothelial cells.

Though clinical trials demonstrated effectiveness of the anti-VEGF antibody bevacizumab (Avastin) in adjuvant therapies for some solid tumours, there are rather few experimental data about cellular effects of bevacizumab on tumour cells and tumour associated endothelial cells. Recent reports demonstrate resistance mechanisms and secondary re-angiogenesis after a transient normalization of tumour vessels. Therefore we investigated the influence of bevacizumab on human glioma cells and human brain derived as well as tumour derived endothelial cells focussing on the role of VEGF-C and -D as potential alternative pro-angiogenic factors. Bevacizumab treatment showed no influence on proliferation after short term exposure (1-5 days) but slowed down endothelial cell proliferation by 25-30% after 14 days treatment. There was no significant induction of apoptosis after short or long term exposure. Tube formation capabilities were significantly impaired by bevacizumab with a continuing effect after 14 days of treatment even after omitting the antibody. VEGF-C and -D had no effect on endothelial cells in untreated or short term treatment groups. However, cells developed responsiveness to these factors in terms of increased proliferation and tube formation after 14 days bevacizumab treatment. Furthermore, bevacizumab induced expression of VEGF-C and -D in glioma cells. Treatment with bevacizumab may induce alterations in human brain and tumour endothelial cells leading to escape mechanisms from anti-VEGF therapy. VEGF-C and -D thus might act as alternative pro-angiogenic factors during anti-VEGF therapy.

Clinical characteristics and outcomes of patients with vancomycin-susceptible Enterococcus faecalis and Enterococcus faecium bacteraemia in cancer patients.

The purpose of this investigation was to compare the risk factors, clinical features and outcomes in cancer patients with bacteraemia caused by vancomycin-susceptible Enterococcus faecalis and E. faecium. A retrospective, observational 7-year study was carried out in a 450-bed, acute-care university-affiliated hospital. We performed univariate comparisons between the two groups and then multivariate analysis to identify patient risk factors for E. faecium isolation. Seventy-three patients were included in the analysis: 54 (74.0%) with bacteraemia caused by E. faecalis and 19 (26.0%) by E. faecium. The Simplified Acute Physiological Score (SAPS) value was significantly greater in E. faecium isolates (40.7 vs. 35.2; p = 0.009). Diabetes mellitus was more frequently diagnosed in patients with E. faecium bacteraemia (52.6% vs. 24.1%; p = 0.021). Prior penicillin exposure was more frequent in patients with E. faecium bacteraemia (68.4% vs. 29.6%; p = 0.003). There was a trend toward higher mortality in E. faecium bacteraemia patients (47.4% vs. 25.9%; p = 0.084). Independent patient risk factors for E. faecium isolation were prior penicillin exposure (odds ratio [OR], 6.479; p = 0.003) and SAPS > 34 (OR, 6.896; p = 0.009). When compared to E. faecalis bacteraemia, E. faecium bacteraemia in cancer patients is independently associated with more severe illness and prior use of penicillins; therefore, empiric treatment which would cover E. faecium should be considered in cancer patients suspected of having bacteraemia.

Economic evaluation of posaconazole vs fluconazole in the prevention of invasive fungal infections in patients with GVHD following haematopoietic SCT.

Posaconazole has been proven to be as effective as fluconazole in the prevention of invasive fungal infections (IFI) in allogeneic haematopoietic SCT patients with GVHD. We assessed, from the perspective of the Spanish National Health Service, the cost-effectiveness of posaconazole vs fluconazole in preventing IFI. A decision-analytic model was developed to assess the average per patient treatment costs, IFIs avoided, life-years gained (LYG) and incremental cost per LYG for each prophylactic treatment used (in euros at 2007 prices). Patients are assumed to have received either posaconazole or fluconazole. The probabilities of IFI, IFI-related death and death from other causes were obtained from a single clinical trial. Long-term mortality and costs were estimated from secondary sources. Posaconazole was associated with fewer IFIs (5.3 vs 9%), increased LYG (8.01 vs 7.78) and higher IFI-related costs ([euro]11 585 vs [euro]6 959) per patient compared with fluconazole. The incremental cost-effectiveness of posaconazole vs fluconazole was estimated at [euro]20 246 per LYG. There was a 70% probability that posaconazole is cost-effective at a [euro]30 000 per LYG threshold. In conclusion, compared with fluconazole, posaconazole prophylaxis is a cost-effective strategy for the prevention of IFI in patients with GVHD.