Brain death due to neuroaspergillosis in a patient with COVID-19.

Co-infections between SARS-CoV-2 and other pathogens is an important consideration for the treatment of patients with COVID-19. Aspergillus infections are part of this consideration since they present high morbidity and mortality. We present the case of a patient with COVID-19 and Aspergillus Fumigatus coinfection that evolves with brain death due to multiple heterogeneous lesions in the brain, which after a post-mortem biopsy found pathological lesions compatible with Aspergillus.

[Brain death due to neuroaspergillosis in a patient with COVID-19]. / Muerte cerebral debida a aspergilosis cerebral en un paciente de COVID-19.

Co-infections between SARS-CoV-2 and other pathogens is an important consideration for the treatment of patients with COVID-19. Aspergillus infections are part of this consideration since they present high morbidity and mortality. We present the case of a patient with COVID-19 and Aspergillus Fumigatus coinfection that evolves with brain death due to multiple heterogeneous lesions in the brain, which after a post-mortem biopsy found pathological lesions compatible with Aspergillus.

Clinical impact of rapid molecular detection of respiratory pathogens in patients with acute respiratory infection.

BACKGROUND: Acute respiratory infections (ARI) are a leading cause of morbidity and mortality worldwide. There is a need to demonstrate the clinical impact of using the new, rapid and sensitive molecular assays in prospectively designed studies. OBJECTIVES: To study the impact on medical management of a rapid molecular assay in patients with respiratory infections. STUDY DESIGN: A prospective, randomized, non-blinded study was performed in patients presenting to the Emergency Department during two respiratory seasons (2016-2017). Diagnosis was performed by FilmArray Respiratory Panel (FilmArray-RP) or by immunofluorescence assay (IFA). RESULTS: A total of 432 patients (156 children and 276 adults) were analyzed. Diagnosis with FilmArray-RP was associated with significant changes in medical management including withholding antibiotic prescriptions (OR:15.52, 95%CI:1.99-120.83 in adults and OR:12.23, 95%CI:1.56-96.09 in children), and reduction in complementary studies in children (OR:9.64, 95%CI:2.13-43.63) compared to IFA. Decrease in oseltamivir prescriptions was significantly higher in adults in the FilmArray-RP group (p = 0.042; OR:1.19, 95%CI:0.51-2.79) compared to adults managed with IFA. Diagnostic yield was significantly higher by FilmArray-RP (81%) than by IFA (31%)(p < 0.001). The median time from sample collection to reporting was 1 h 52 min by FilmArray-RP and 26 h by IFA (p < 0.001). CONCLUSIONS: The high respiratory viruses' detection rate and availability of results within two hours when using FilmArray-RP were associated with decreases in antibiotic prescriptions and complementary studies and more accurate use of oseltamivir.

Las alteraciones de la microbiota intestinal en la patogenia del hígado graso no alcohólico / Alterations of the intestinal microbiota in the pathogenesis of nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is currently considered in Chile and worldwide, as the main cause of cirrhosis and liver transplantation. It is therefore one of the main public health objectives for reducing its prevalence. In last years, it was suggested that the intestinal microbiota (IM) might contribute to the pathophysiology of NAFLD, as well as in the progression toward nonalcoholic steatohepatitis (NASH) and cirrhosis. It is known that changes in the composition of IM are associated with alterations in intestinal permeability and the production of inflammatory metabolites. These alterations are part of the pathophysiological mechanisms leading to the development of NASH. However studies on MI in patients with NAFLD and NASH in Chile are scarce. Through a research grant, recently awarded at the Hospital Clínico Universidad de Chile, we aim to confirm and characterize the intestinal dysbiosis associated with NAFLD in Chilean patients and to establish the relationship between the changes in microbial composition with the progression of liver damage. The description of these alterations represents an opportunity to explore new therapeutic approaches for future interventions. In effect, through the restoration of an intestinal microbial environment towards homeostasis in these patients, we expect to reverse or improve the progression of damage provoked by this disease. (AU)

Two-year experience with tacrolimus in renal transplantation after late conversion from cyclosporine therapy.

INTRODUCTION: Calcineurin inhibitors are associated with chronic allograft nephropathy. Protocols to reverse nephrotoxicity incorporate dosage reduction or withdrawal of these agents. Using ketoconazole as a sparing agent with mean cyclosporine doses of less than 50 mg/d, we have usually observed adverse cosmetic effects. One cohort of patients exhibited severe gingival hyperplasia that required gum resection; some also had hypertricosis. OBJECTIVE: To evaluate the effects of conversion from cyclosporine (CsA) to a tacrolimus generic formulation (TAC) in patients with adverse cosmetic effects from CsA. PATIENTS AND METHODS: Twenty-three patients were studied at a mean (SD) of 56 (48) months posttransplantation; serum creatinine concentration was 1.91 (0.68) mg/dL. All had eyebrow and facial hypertricosis, and 10 also had gum hyperplasia. Cyclosporine C0 or C2 levels and CsA dosage had previously been changed simultaneously with ketoconazole. The day after withdrawal of CsA, TAC therapy was started at a dose of 0.065 to 0.030 mg/kg/d. Patients were followed up for 18 months (12.76 [7.57]) with routine laboratory tests. RESULTS: Twenty patients without proteinuria demonstrated improved renal function at 1-month follow-up; serum creatinine concentration was 1.76 (0.42) mg/dL vs 1.47 (0.37) mg/dL (P < .02). Levels of tacrolimus were 13.82 (7.95) ng/mL at 15 days and 7.3 (3.5) ng/mL at 2 months after the dosage was decreased to 0.042 mg/kg/d. Gum hypertrophy and hypertrichosis resolved in all patients. One patient died 18 months after conversion of cardiovascular disease and chronic allograft nephropathy. Neither diabetes nor dislipidemia were noted. CONCLUSION: Generic TAC is a good therapeutic alternative in renal transplant recipients with adverse reactions to CsA.

Converting to a generic formulation of mycophenolate mofetil in stable kidney transplant recipients: 1 year of drug surveillance and outcome.

OBJECTIVE: The objective of this study was to compare the pharmacokinetic profiles of a generic formulation with the innovator mycophenolate mofetil (MMF). METHODS AND PATIENTS: Thirteen patients with stable renal grafts received MMF posttransplantation (mean, 32 months; confidence interval 95%: 51, 9-12, 36). Graft function improved significantly (serum creatinine levels 2.72 +/- 1.75 mg/dL to 1.9 +/- 0.66 and 1.79 +/- 0.86 mg/dL at 12 and 30 months, respectively; P < .05). Three point (basal, 2, and 6 hours) profiles were performed. Five patients were switched 1:1 to a generic formulation for 60 days and repeating the pharmacokinetics were repeated. Afterwards, they returned to the innovator MMF for 45 days. Finally, all patients received generic MMF, repeating the pharmacokinetics between 15 days and 6 months later. RESULTS: The area under the curve (AUC 0-6) of MPA was 52.68 +/- 17.5 microg/mL*hr, with 61.5% of basal determinations (Co) under 5 microg/mL (4.08 +/- 0.74). The Pearson correlation coefficient was high between both MMF formulations regarding FMPA AUC 0.768 (P < .005), Co (0.774; P < 0.05), and C6 (0.996; P < .005). GMPA AUC were similar (Pearson) 0.7 (P < .01), Co 0.99 (P < .01), and C6 0.86 (P < .01). C2 MMF levels were variable and showed poor correlation. FMPA AUC of generic and original formulations after 60 days had tight correlation. (Pearson 0.883; P < .025) and comparing 15 and 60 days postconversion with generic drug in the same patients were similar (Pearson 0.58; P < .025). Renal function at 12 months remained stable postconversion. CONCLUSIONS: Conversion to generic MMF in stable renal transplant recipients showed good clinical results.

Hepatotoxicity associated with cyclosporine monitoring using C2 recommendations in adults renal recipients receiving ketoconazole.

Following the change, in the way we monitored cyclosporine (CsA) levels in January 2000 namely from C0 to C2 concentrations, in renal "de novo" allograft recipients, some patients treated with concomitant ketoconazole experienced liver toxicity, a complication that had not been previously seen with CsA monitoring using C0. Therefore, we decided to compare the outcomes of patients transplanted using CsA levels monitored by C0 (1998 to 1999) who also had simultaneous C2 determinations (group A) with those of recipients transplanted after 2000 (group B). All received steroids, azathioprine, and CsA plus ketoconazole. Recipients were followed for at least a year after transplantation. Patients in group B showed higher CsA C2 levels, AUC concentrations, and drug doses during the immediate postsurgical period, and at 2 weeks as well as 4 and 6 months posttransplantation. Six group B patients (26%) but no group A recipients displayed, severe liver toxicity characterized by jaundice, elevated liver enzymes, with negative serological tests for CMV, HVC, and HVB. There was a correlation between the GOT and the C2 CsA levels; both normalized 15 to 55 days after CsA dose reduction. High C2 CsA levels, which have been recommended when the drug is used alone in renal transplantation, cannot be used in patients taking ketoconazole, because C2 neither represents nor correlates with AUC drug exposure. Thus high C2 levels may produce liver toxicity.

Multicentered study of viral acute lower respiratory infections in children from four cities of Argentina, 1993-1994.

This study describes the first multicentered study of acute lower respiratory infection viral etiology in young children from four different geographical areas of Argentina. A total of 1,278 children under 5 years of age, hospitalized in primary care centers from Buenos Aires, Córdoba, Santa Fé and Mar del Plata cities during a 2-year period were studied (1993-1994). Nasopharyngeal aspirates were investigated for respiratory syncytial virus (RSV), adenovirus, parainfluenza, and influenza A and B viruses by indirect immunofluorescence. Out of the patients studied, 946 (74%) were under 1 year of age. Viruses were detected in 399 patients (32%). RSV was observed in 25.3% of the samples, representing 78.2% of all viral positive cases. Adenoviruses were detected in 2.5% of the cases, parainfluenza in 2.2%, influenza A in 2.1%, and influenza B in 0.2%. Compared with other viruses, the higher RSV frequency was statistically significant (P < 0.000). Most RSV cases were detected between May and September with a significant peak in July (P < 0.000). Pneumonia was observed in 46% of the patients, bronchiolitis in 41% and other entities in 13%. The case fatality rate observed during the 2 year study was 0.73%. Most of the above respiratory viruses were detected in the four cities, however, the frequency of RSV and influenza were different in the southern city.

[Cytomegalovirus isolation by conventional cell culture and shell vial assay]. / Aislamiento de citomegalovirus por cultivo convencional y cultivo rápido.

In immunocompromised patients, diagnosis of Cytomegalovirus (CMV) active infection is of utmost importance for the initiation, monitoring and ending of antiviral therapy. Therefore, the presence of viral replication should be demonstrated. Isolation in tissue culture is one of the standard methods. The objective of the present paper was to compare two isolation procedures for CMV: conventional cell culture (CC) and rapid shell vial (SV) assay in human fibroblasts. A total of 584 clinical samples were studied between 1991 and 1998. CMV was isolated in 14.4% of the samples, 11.8% of which were positive by SV and 7.7% by CC. Out of 84 positive samples, concordance between both methods was observed in 36% of the cases. We found that 46% of the samples were positive only by SV, while 18% were positive only by CC. The average time required for obtaining the results by CC was 22.6 +/- 2.3 days. Out of the 69 samples positive by SV, 43% were already positive after 24 hours and the rest after 48 hours. These results indicate that SV was more sensitive and rapid than CC. The main advantage of CC, despite its time-consuming process, is the ability to recover the viral strain for both antiviral susceptibility phenotypical tests and strain characterization. Furthermore, in this study, absence of CC would have resulted in the loss of 18% of the positive diagnoses. In conclusion, simultaneous use of both methods is suggested in order to obtain a rapid result and the highest sensitivity.

Aislamiento de citomegalovirus por cultivo convencional y cultivo rápido. / [Cytomegalovirus isolation by conventional cell culture and shell vial assay]

In immunocompromised patients, diagnosis of Cytomegalovirus (CMV) active infection is of utmost importance for the initiation, monitoring and ending of antiviral therapy. Therefore, the presence of viral replication should be demonstrated. Isolation in tissue culture is one of the standard methods. The objective of the present paper was to compare two isolation procedures for CMV: conventional cell culture (CC) and rapid shell vial (SV) assay in human fibroblasts. A total of 584 clinical samples were studied between 1991 and 1998. CMV was isolated in 14.4

of the samples, 11.8

of which were positive by SV and 7.7

by CC. Out of 84 positive samples, concordance between both methods was observed in 36

of the cases. We found that 46

of the samples were positive only by SV, while 18

were positive only by CC. The average time required for obtaining the results by CC was 22.6 +/- 2.3 days. Out of the 69 samples positive by SV, 43

were already positive after 24 hours and the rest after 48 hours. These results indicate that SV was more sensitive and rapid than CC. The main advantage of CC, despite its time-consuming process, is the ability to recover the viral strain for both antiviral susceptibility phenotypical tests and strain characterization. Furthermore, in this study, absence of CC would have resulted in the loss of 18

of the positive diagnoses. In conclusion, simultaneous use of both methods is suggested in order to obtain a rapid result and the highest sensitivity.

Respiratory syncytial virus: changes in prevalence of subgroups A and B among Argentinian children, 1990-1996.

The frequency of respiratory syncytial virus (RSV) and the distribution of subgroups A and B strains during 7 consecutive years (1990-1996) were examined in two cities of Argentina. Nasopharyngeal aspirates from 1,304 children less than 2 years of age hospitalized with acute lower respiratory infection were studied by indirect immunofluorescence. RSV was detected in 352 cases (26.9%), and the peak activity was observed in midwinter. Subgroup characterization was performed with two monoclonal antibodies against the F protein on nasopharyngeal aspirate smears. Of 195 samples, 174 (89.2%) were identified as subgroup A strains and 21 (10.8%) as subgroup B. Both strains cocirculated during 5 of 7 years studied with subgroup A predominating. Subgroup A occurred at least 8 times as often in all years except for 1994-1995. Children infected by subgroup A were younger than those infected by subgroup B (P < 0.05). The association of subgroup A infection with bronchiolitis and subgroup B with pneumonia was statistically significant (P < 0.03).

Clinical and epidemiologic characteristics of respiratory syncytial virus subgroups A and B infections in Santa Fe, Argentina.

Respiratory Syncytial Virus (RSV) has two major antigenic groups, A and B. The implications of these variants in the epidemiology and pathogenesis of RSV infection are not well defined. This study was undertaken to compare the two RSV subgroups in patients admitted to hospital. Clinical and epidemiologic features of RSV subgroups in children under 30 months of age with proven RSV acute lower respiratory infections were examined during 4 winters from 1993 to 1996 in Santa Fe, Argentina. RSV typing was carried out with monoclonal antibodies in nasopharyngeal cells by indirect immunofluorescence. Of the 177 RSV positive nasopharyngeal aspirates obtained from 1993 to 1996, 85 (48%) were available for typing. Seventy-three (85.9%) specimens were identified as Subgroup A and 12 (14.1%) as Subgroup B. Except in 1993, in which only Subgroup A was detected, both variants circulated throughout the epidemic season. Subgroup A infections produced more severe disease than Subgroup B infections, as assessed by the length of the hospital stay and the use of respiratory support. This difference was age related, being evident in infants 0-6 months old. Patients with Subgroup B infections were also significantly less frequently breast-fed (95% vs. 75% for A and B subgroups, respectively; P = 0.04). It is concluded that the severity of disease in Argentinian patients admitted with acute RSV infections may be associated with Subgroup A strains as determined by a serogrouping method.

Genomic analysis of adenovirus isolated from Argentinian children with acute lower respiratory infections.

BACKGROUND: Adenoviruses are the second cause of acute lower respiratory infection (ALRI) of viral origin in small children from Buenos Aires, Argentina. OBJECTIVE: The aim of this study was to characterize, by restriction enzyme analysis, 17 adenovirus strains isolated from the nasopharyngeal aspirates of children under 2 years of age hospitalized due to ALRI. STUDY DESIGN: Seventeen adenovirus strains isolated between May 1991 and December 1992 in one hospital of Buenos Aires were studied. Adenoviruses were amplified in HEp-2 cells and viral DNA was studied with the restriction enzymes Bam HI and Sma I. RESULTS AND CONCLUSIONS: Eighty two percent (14/17) of the isolates were classified as adenoviruses from subgenus b and 17.7% (3/17) belonged to subgenus c. Genome type 7 h was detected in 85.7% (12/14) and 7 i in 14.3% (2/14) of the strains from subgenus b. The case lethality associated with adenovirus genome type 7 was 28.6% (4/14 cases). Three fatal cases corresponded to Ad 7 h and one to Ad 7i. Ad 7h shows a high prevalence in small children hospitalized with ALRI and is associated with a high fatality rate.

Relevancia clínica de los diferentes métodos diagnósticos para citomegalovirus / Clinical relevance of different idagnostic methods in citomegalovirus diagnosis

This review article details the clinical relevance of different diagnostic methods in citomegalovirus diagnosis

Relevancia clínica de los diferentes métodos diagnósticos para citomegalovirus / Clinical relevance of different idagnostic methods in citomegalovirus diagnosis

This review article details the clinical relevance of different diagnostic methods in citomegalovirus diagnosis

Acute lower respiratory infections due to respiratory syncytial virus and adenovirus among hospitalized children from Argentina.

BACKGROUND: Acute lower respiratory infection (ALRI) is one of the main causes of morbidity and mortality in small children. OBJECTIVE: The aim of this study was to determine the frequency, seasonality and association with clinical entities of respiratory syncytial virus (RSV) and adenoviruses in children with ALRI. STUDY DESIGN: During 2 consecutive years (1991-1992), 168 children under 2 years of age hospitalized due to ALRI in a public pediatric hospital of Buenos Aires, Argentina, were studied. RSV and adenoviruses were investigated on nasopharyngeal aspirates (NPA) by indirect immunofluorescence (IIF). HEp-2 cells were used for adenovirus isolation. RESULTS: RSV was detected in 36.3% and adenoviruses in 14.3% of the cases (P < 0.0001). All adenoviruses detected by IIF were also isolated in culture. Out of 61 RSV cases, 57% corresponded to bronchiolitis and 43% to pneumonia. Ninety-two per cent of children with RSV were less than 1 year old and 70% were less than 5 months. The highest number of RSV cases were observed during winter, with a clear peak in July. Seventy-one per cent of adenovirus cases were associated with pneumonia and only 24% with bronchiolitis (P < 0.02), and predominated in children older than 5 months of age (P < 0.0001). Adenoviruses were detected in almost all months of the year with a small peak at the end of winter and beginning of spring. No significant differences in clinical features at admission, breast feeding or malnutrition were observed among children with RSV or adenovirus diagnosis versus those with no viral etiology. The overall fatality rate was 2.4%. In all fatal cases adenovirus was detected in NPA. Thus, fatality rate among patients with adenoviruses reached 16.7%. CONCLUSIONS: Our findings show the importance of RSV and adenoviruses associated with ALRI in hospitalized children under 2 years of age and the different epidemiological patterns of the two viruses in Buenos Aires, Argentina.

[Conversion from +Sandimmune to Neoral in kidney transplant recipients treated with cyclosporine and ketoconazole]. / Conversión de Sandimmune a Neoral en pacientes trasplantados renales que reciben ciclosporina-ketoconazol.

BACKGROUND: Microemulsion cyclosporine is a new pharmaceutical form whose intestinal absorption is more constant, resulting in a better bioavailability. AIM: To assess dose adjustments and variability of blood levels after the conversion of cyclosporine to microemulsion cyclosporine in renal transplant recipients function receiving cyclosporine-ketoconazole. PATIENTS AND METHODS: Thirty four patients with more than one year after the transplantation, with stable renal function and receiving triple immunosuppression were studied. Conventional cyclosporine was changed to the microemulsion form maintaining the same daily dose. Drug serum levels, serum creatinine and blood pressure were measured within two to eight months after the conversion. Doses of microemulsion cyclosporine were adjusted to achieve serum levels of 150 +/- 40 ng/ml. RESULTS: Microemulsion cyclosporine induced a slight initial increase in blood cyclosporine levels. Afterwards, levels were more stable than with conventional cyclosporine (165-185 and 145-210 ng/ml respectively) and the dispersion of values were lower (standard deviations of 70 and 100 ng/ml respectively). Twenty three patients did not require dose adjustments, in four it was reduced and in five it was increased. There were no changes in serum creatinine or blood pressure after the conversion. CONCLUSION: More stable serum levels without adverse reactions were obtained with microemulsion cyclosporine. Doses of cyclosporine need not to be changed during the conversion.

[Acute kidney failure in patients with and without sepsis: prognosis and clinical course]. / Insuficiencia renal aguda en pacientes con y sin sepsis: pronóstico y evolución.

The purpose of this prospective study was to determine whether the course and prognosis of acute renal failure (ARF) in patients with and without sepsis are different. Two hundred fifty-two (8%) of 3086 consecutive patients admitted to a medical-surgical intensive care unit (ICU) developed ARE. One hundred forty-nine (59%) were septic and 103 (41%) were non-septic. No differences were found between groups regarding the incidence of oliguria, hyperkalemia, hypercatabolism, gastrointestinal bleeding, duration of oligria and renal deficit, severity of axotemia, dialysis requirements and duration of stay in the hospital. There were statistically significant differences between septic and non septic patients with respect of hyponatremia (67.8 vs 54.4%, p < 0.04), respiratory failure (68 vs 54%, p < 0.04), and thrombocytopenia (64 vs 48%, p < 0.02). Mortality in septic patients was higher than in non-septics (56 vs 42.7%, p < 0.009). Factors associated with increased mortality in ARF septic patients were respiratory failure, metabolic acidosis and oliguria while in the non-septics they were hepatic dysfunction, hyperkalemia, respiratory failure and infection acquired during the course of renal failure. We conclude that ARF developing in septic patients has a higher mortality than that of non-septic patients, whereas the incidence of hypercatabolism and oliguria was not different between both groups.

Molecular epidemiology of adenovirus acute lower respiratory infections of children in the south cone of South America (1991-1994).

A collection of 165 adenovirus strains isolated from nasopharyngeal aspirates of children hospitalized for acute lower respiratory infection in Argentina, Chile, and Uruguay between 1991 and 1994 was studied by restriction enzyme analysis (work performed in the Department of Virology, University of Umeå). Of the isolates, 71% (n = 117) were identified as members of subgenus B. Of these, 101 (61.2%) corresponded to genome type 7h, four (2.4%) to genome type 3p2, four (2.4%) to genome type 11a, one (0.6%) to genome type 7b, and one (0.6%) to genome type 7c. Two isolates that were neutralized as serotype 3 and four isolates that were neutralized as serotype 7 exhibited novel BamHI cleavage profiles corresponding to three new genome types denominated 3x, 7i, and 7j. Subgenus C members represented 28.5% of all typed isolates. Five different genome types of Ad1, seven genome types of Ad2, and three genome types of Ad5 were identified of, which two, two, and one, respectively, were found to correspond to new DNA variants. Only one isolate (0.6%) corresponded to Ad4 of subgenus E. Ad7h was isolated from 17 of the 18 fatal cases recorded among the patients included in the study.