Landscape of Invasive Fusariosis in Pediatric Cancer Patients: Results of a Multicenter Observational Study From Latin America.

Invasive fusariosis (IF) is a life-threatening opportunistic infection that affects vulnerable hosts. We conducted a multicenter and multinational retrospective study to characterize the natural history and clinical management of IF in pediatric cancer patients. We selected patients <18 years old who were sequentially hospitalized in 10 Latin American medical centers with a diagnosis of IF between 2002 and 2021. Data were collected using an electronic case report form complemented by a dictionary of terms. We assessed mortality rates at 30, 60, and 90 days. We collected data from 60 episodes of IF (median age, 9.8 years) that were mostly documented in patients with hematologic cancer (70%). Other risk conditions found were lymphopenia (80%), neutropenia (76.7%), and corticosteroid exposure (63.3%). IF was disseminated in 55.6% of patients. Skin lesions was present in 58.3% of our patients, followed by pulmonary involvement in 55%, sinusitis in 21.7%, bone/joint involvement in 6.7% and 1 case each of endocarditis and brain abscess. Positive blood and skin biopsy cultures were detected in 60% and 48.3% of cases, respectively. Fusarium solani complex was the most commonly identified agent (66.6%). The majority of patients received monotherapy within the first 72 hours (71.6%), either with voriconazole or amphotericin B formulation. The mortality rates at 30, 60, and 90 days were 35%, 41.6%, and 45%, respectively. An important factor affecting mortality rates appears to be disseminated disease. The high percentage of patients with fungal involvement in multiple organs and systems highlights the need for extensive workup for additional sites of infection in severely immunocompromised children.

Vertical structure of reef fish assemblages and light penetration reveal new boundaries of mesophotic ecosystems in the subtropical Southwestern Atlantic.

In the Southwest Atlantic, fisheries and in situ observations suggest that mesophotic reefs occur further south than has been reported in the literature, and a description of these subtropical regions is still lacking. We used Baited Remote Underwater stereo-Videos to explore unrevealed patterns in the vertical structure of fish assemblages on subtropical Atlantic reefs, contrasting shallow and mesophotic habitats. Our data on species turnover and light penetration reveal that in the subtropical Atlantic, the boundaries between shallow and mesophotic habitats occur at depths of 18 m, which is shallower than most previous studies have shown. Generalized additive mixed models identified different environmental and management factors as important predictor variables that explain distribution of fish assemblages' attributes. Besides adding new evidence about mesophotic limits, we described variations in the vertical structure of fish assemblages, providing important information for the description and conservation of mesophotic environments in subtropical regions.

Proxies to detect hotspots of invertebrate biodiversity on rhodolith beds across the Southwestern Atlantic.

Rhodolith beds are known worldwide to host high biodiversity to several taxa. Despite their importance, few ecological data explored the influence of rhodolith features and environmental variables on associated biodiversity, a gap that has been hampering the mapping of diversity hotspots and priority areas for conservation. In this study, we investigated large-scale spatial variations of rhodolith beds and their associated fauna, using annelid polychaetes as a biological model. We aimed to identify proxies, based on rhodolith features and environmental variables, to detect biodiversity hotspots across Southwestern Atlantic beds, laying the groundwork for mapping priority areas for conservation. With this goal, we sampled a total of 136 rhodolith nodules across seven sites with beds under distinct latitudes, depths, distances from the mainland coast of Brazil, and rhodolith densities. For each nodule sampled, we measured the volume, diameter, and mass of sediment trapped, as well as the attributes of the associated polychaetes (abundance, richness, diversity, and composition). Our results revealed a complex network of collinearities and synergisms between the rhodolith features and the majority of the polychaetes attributes (i.e., abundance, diversity, and composition). Polychaete richness, in contrast, can be explained by the combination of two proxies: (1) rhodolith nodule diameter and (2) distance of the rhodolith bed from the mainland coast. Nearshore rhodolith beds and larger nodules were associated with higher values of richness. Additionally, rhodoliths with a hollow morphology were also associated with higher values of polychaete richness. These results suggest that nearshore rhodolith beds with large and hollow nodules could be priority areas for conservation. However, further multi-taxa studies using our framework are still needed to explore other regions and scales, delineating more comprehensive proxies for predicting ecological patterns of the rhodoliths associated fauna and to identify priorities for conservation across Southwestern Atlantic beds.

High-risk clones of carbapenem resistant Klebsiella pneumoniae recovered from pediatric patients in Southern Brazil.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) exhibit high mortality rates in pediatric patients and usually belong to international high-risk clones. This study aimed to investigate the molecular epidemiology and carbapenem resistance mechanisms of K. pneumoniae isolates recovered from pediatric patients, and correlate them with phenotypical data. Twenty-five CRKP isolates were identified, and antimicrobial susceptibility was assessed using broth microdilution. Carbapenemase production and ß-lactamase genes were detected by phenotypic and genotypic tests. Multilocus sequence typing was performed to differentiate the strains and whole-genome sequencing was assessed to characterize a new sequence type. Admission to the intensive care unit and the use of catheters were significantly positive correlates of CRKP infection, and the mortality rate was 36%. Almost all isolates showed multidrug-resistant phenotype, and most frequent resistant gene was blaKPC. We observed the dissemination of ST307 and clones belonging to CG258, which are considered high risk. In pediatric patients, these clones present with high genomic plasticity, favoring adaptation of the KPC and NDM enzymes to healthcare environments.

Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study.

PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. FINDINGS: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. IMPLICATIONS: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

Outbreak of vancomycin-resistant Enterococcus faecium ST1133 in paediatric patients with acute lymphoblastic leukaemia from southern Brazil.

OBJECTIVES: We aimed to investigate an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) in paediatric patients from Hospital Pequeno Príncipe. The susceptibility profile was determined, and whole-genome sequencing (WGS) was used to analyse the genetic context of the strains. METHODS: Five VREfm isolates were recovered from sterile sites and surveillance cultures of two paediatric patients with acute lymphoblastic leukaemia. Species identification was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and the minimum inhibitory concentration (MIC) was assessed according to the European Committee for Antimicrobial Susceptibility Testing (EUCAST). WGS was performed to analyse the genetic context of virulence and resistance genes, and in silico multilocus sequence typing was performed to identify the sequence typing of the strains. RESULTS: High-level vancomycin resistance was observed in all isolates (≥256 mg/L). WGS revealed the presence of mobile genetic elements, such as plasmids (rep2, rep11a, repUS15, rep17, and rep18a), insertion sequences, and phages. Multiple resistance genes (aac(6')-aph(2"), dfrG, ermB, and vanA) and virulence genes (acm and efaAfm) were identified. All the isolates were assigned to ST117 (ST1133 - via a novel MLST), an important epidemic lineage associated with nosocomial infections and outbreaks. CONCLUSION: Our results show that the ST117 (ST1133) VREfm isolates are circulating in paediatric patients, which raises a great concern. The development of new drugs as well as the implementation of an antimicrobial stewardship program are necessary for their correct management, limiting the spread of resistance in oncohematological patients.

Analysis of Clostridioides difficile Infection in Children with Diarrhea in Two Hospitals in Southern Brazil.

Clostridioides difficile infection (CDI) has been increasingly observed in children, but there is a lack of epidemiological and molecular data on CDI in Latin America. This prospective cohort study aimed to investigate the role of CDI in children with diarrhea. It included 105 children with antimicrobial-associated diarrhea (AAD) and analyzed the molecular characteristics of strains isolated from two hospitals in southern Brazil between 2017 and 2020. Fecal samples from the participants were tested for glutamate dehydrogenase (GDH) and A/B toxins using a rapid enzyme immunoassay. GDH-positive samples underwent automated real-time polymerase chain reaction and toxigenic culture. Toxigenic C. difficile isolates were selected for whole genome sequencing. Out of the 105 patients, 14 (13.3%) met the criteria for CDI. Children with a history of previous CDI and the presence of mucus in their stool were more likely to have CDI. Metronidazole was the most used treatment (71.4%), and three patients (23.1%) experienced CDI recurrence (rCDI). Although the number of sequenced isolates was limited, a wide diversity of sequence types (ST) was observed. In addition to toxin genes (tcdA, tcdB, cdtA, and cdtB), the isolates also exhibited virulence factors involved in adhesion (cwp66, groEL, slpA, fbpA/fbp68) and immune evasion (rmlA, rmlB, rmlC, gnd, rfbA-1), along with multiple resistance factors (gyrA mutation, norA, ermB, dfrF, and vanG). These findings highlight the prevalence and recurrence of CDI among hospitalized children. Longitudinal studies are needed to better understand the characteristics of CDI-associated diarrhea and its impact on the healthcare system in this population.

Pancreatic Neuroendocrine Tumor (Pan-NET) Presented by Abdominal Pain: A Case Report and Literature Review.

A pancreatic neuroendocrine tumor (Pan-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional Pan-NETs, typically when liver metastases occur. In this paper, we describe the case of a patient with a low-grade non-functional Pan-NET, but with a typical clinical presentation of carcinoid syndrome. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools, and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hyper-vascular mass; then, a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum chromogranin A and urinary 5-HIAA measurements were negative. We performed an endoscopic ultrasonography (EUS) by a fine-needle biopsy (EUS-FNB), allowing the immunostaining of a small mass (0.8 cm) and the diagnosis of a low-grade (G1) non-functional Pan-NET (NF-Pan-NET). Surgery was waived, while a follow-up strategy was chosen. The early recognition of Pan-NETs, although rare, is necessary to improve the patient's survival. Although helpful to allow for immunostaining, EUS-FNB needs to be warranted in future studies comparing EUS-FNB to EUS-FNA (fine-needle aspiration), which is, to date, reported as the tool of choice to diagnose Pan-NETs.

Modeling risks in marine protected areas: Mapping of habitats, biodiversity, and cultural ecosystem services in the southernmost atlantic coral reef.

Marine Protected Area (MPA) is a fundamental strategy for the maintenance of ocean ecological processes worldwide and, consequently, their associated ecosystem services. Nevertheless, the quality of the services provided by MPAs, including cultural services such as recreational activities, depends on the effective management of marine habitats and biodiversity. Here, we performed an ecosystemic assessment in reef environments within a subtropical MPA, modeling the potential risks for their habitats and their recreational activities. The Queimada Grande Island (QGI), southeastern Brazil, was used as the model area since this island encompasses a unique and irreplaceable marine habitat, the Southernmost Atlantic coral reef. We firstly assessed and mapped the habitats, the biodiversity, and the recreational activities associated with QGI reefs. Next, we considered different scenarios of management for the modeling risks across the study area. We found that the coral reef and its adjacent habitats, such as the rhodolith bed, make the sheltered face of the island an important area for the provision of the cultural ecosystem services and overlapping uses such as onboard recreational fishing, spearfishing, and recreational diving. This area was also evaluated as the one under the highest risk of impact, considering the current scenario of management. The most successful scenario modeling to reduce these risks was the hypothetical implementation of a 66% reduction of all activities over all QGI habitats. Despite that, the scenario simulating the application of the regulations present in the MPA management plan was enough to reduce almost half the maximum risk value. Therefore, we concluded that to provide a balance among conservation, uses, and the local economy, the application of these regulations is the better management scenario modeled for the study area. Such results provided useful information and tools for local management and decision-making in this singular marine environment, also being an example for mapping ecosystem services and modeling risks in MPAs worldwide.

Effects of the COVID-19 pandemic on SCUBA diving experience in marine protected areas.

Faced with the need for isolation of most people to reduce the transmission of COVID-19, a great concern for the well-being of the population has resurfaced. Considering the numerous benefits of outdoor activities to human health and well-being, we assessed whether the quality of the experience of recreational divers in a marine protected area (MPA) was impacted during the pandemic. We applied a semi-structured questionnaire to divers, collected their socioeconomic profile, preferences, motivations, experiences, and compared the results with those obtained in the previous season. We found that the quality of the recreational diver's experience remained high even during one of the world's biggest health crises. This suggests that the combination of contact with a preserved environment and the adaptation of regulations in favor of visitor safety was enough to stimulate positive experiences. Therefore, we highlight the importance of investing in adaptive management so that MPAs continue to promote ecosystem services such as human health and subjective well-being. Management implications: •Quality of experience for recreational divers remained high and was unaffected after the first major wave of COVID-19 cases.•Through adaptive tourism management, MPAs can promote positive experiences even in challenging contexts.•High impact of environmental attributes on the quality of divers' experience reinforces that threats to ecosystems are social impacts.•Socially unequal access to benefits generated by MPAs may negatively influence population's support for these areas.•Efforts are needed to strengthen the equity of distribution of positive social impacts in MPAs.•Potential to provide positive experiences for users must be seen beyond economic value, but as an investment in the population's subjective well-being.

Assessment of Pediatric Telemedicine Using Remote Physical Examinations With a Mobile Medical Device: A Nonrandomized Controlled Trial.

Importance: The number of innovations in health care based on the use of platforms, digital devices, apps, and artificial intelligence has grown exponentially in recent years. When used correctly, these technologies allow inequities in access to health care to be addressed by optimizing care and reducing social and geographic barriers. However, most of the technological health care solutions proposed have not undergone rigorous clinical studies. Objective: To assess the concordance between measurements from a remote physical examination using a mobile medical device and measurements from a conventional in-person physical examination. Design, Setting, and Participants: This nonrandomized controlled trial was conducted from January 1 to December 31, 2020. The clinical parameters compared were heart rate; body temperature; heart, lung, and abdominal auscultation; otoscopy; throat and oral examination; and skin examination. A total of 690 patients with clinical stability and various symptoms who were seen in the emergency department of 2 Brazilian pediatric hospitals were eligible to enter this study. Main Outcomes and Measures: The primary outcome was concordance between measurements from a telemedicine physical examination using a mobile medical device and measurements from a conventional in-person physical examination. The secondary outcome was the specificity and sensitivity of the digital device, considering the conventional in-person consultation as the gold standard. Results: Among 690 patients, the median (IQR) age at study entry was 5 (1-9) years; 348 (50.4%) were female, and 331 (48.0%) presented with a chronic disease. Regarding the primary outcome, the concordance values were 90% or greater for skin examination (94% for rash, 100% for hemorrhagic suffusion, and 95% for signs of secondary infection), characteristics of the mucosa (98% for hydration and 97% for coloring), and heart (95% for murmur, 97% for rhythms, and 98% for sounds), lung (91% for adventitious sounds, 97% for vesicular sounds, and 90% for fever), and abdominal (92% for abdominal sounds) auscultations. Concordance values were lower for otoscopy (72% for the ear canal and 86% for the tympanic membrane), throat and oral examination (72%), and rhinoscopy (79% for mucosa and 81% for secretion). The specificity was greater than 70% (ranging from 74.5% for the ear canal to 99.7% for hemorrhagic suffusion) for all variables. The sensitivity was greater than 52% for skin examination (58.0% for rash and 54.8% for signs of secondary infection), throat and oral examination (52.7%), and otoscopy (66.1% for the ear canal and 64.4% for the tympanic membrane). Conclusions and Relevance: In this study, measurements from remote physical examination with a mobile medical device had satisfactory concordance with measurements from in-person physical examination for otoscopy, throat and oral examination, skin examination, and heart and lung auscultation, with limitations regarding heart and lung auscultation in infants and abdominal auscultation in children of all ages. Measurements from remote physical examination via a mobile medical device were comparable with those from in-person physical examination in children older than 2 years. These findings suggest that telemedicine may be an alternative to in-person examination in certain contexts and may help to optimize access to health care services and reduce social and geographic barriers. Trial Registration: Brazilian Registry of Clinical Trials Identifier: RBR-346ymn.

Saprochaete clavata invasive infection: characterization, antifungal susceptibility, and biofilm evaluation of a rare yeast isolated in Brazil.

Rare emerging pathogens such as Saprochaete clavata are associated with invasive fungal diseases, high morbidity, mortality, rapidly fatal infections, and outbreaks. However, little is known about S. clavata infections, epidemiology, risk factors, treatment, biofilms, and disease outcomes. The objective of this study was to describe a new case of severe S. clavata infection in a patient diagnosed at a referral children's hospital in Brazil, including antifungal minimal inhibitory concentration, S. clavata biofilm characterization, and molecular characterization. The S. clavata isolated from an immunocompromised 11-year-old male patient was characterized using MALDI-TOF, Gram staining, scanning electron microscopy (SEM), and next generation sequencing (NGS) of genomic DNA. Biofilm production was also evaluated in parallel with determining minimal inhibitory concentration (MIC) and biofilm sensitivity to antifungal treatment. We observed small to medium, whitish, farinose, dry, filamentous margin colonies, yeast-like cells with bacillary features, and biofilm formation. The MALDI-TOF system yielded a score of ≥ 2,000, while NGS confirmed S. clavata presence at the nucleotide level. The MIC values (in mg L-1) for tested drugs were as follows: fluconazole = 2, voriconazole ≤ 2, caspofungin ≥ 8, micafungin = 2, amphotericin B = 4, flucytosine ≤ 1, and anidulafungin = 1. Amphotericin B can be active against S. clavata biofilm and the fungus can be susceptible to new azoles. These findings were helpful for understanding the development of novel treatments for S. clavata-induced disease, including combined therapy for biofilm-associated infections.

Immune reconstitution after allogenic stem cell transplantation: An observational study in pediatric patients.

INTRODUCTION: The immune reconstitution (IR) after the allogenic hematopoietic stem cell transplantation (allo-HSCT) is a progressive process intrinsically correlated to the therapeutic success. It is essential to understand the interfering factors in IR to prevent the HSCT-related mortality. METHODS: We retrospectively evaluated the clinical outcomes, absolute lymphocyte counts (ALCs) and lymphocyte subtypes at different time-points of 111 pediatric patients with allogeneic HSCT for malignant and non-malignant diseases from 2013 to 2018. RESULTS: The ALCs gradually increased on D+30, D+100, and D+180 (medians 634/µL, 1022/µL and 1541/µL, respectively). On D+100, the CD3+CD8+ achieved the highest recovery rate (68%), followed by the CD16+CD56+ (47%), CD3+CD4+ (39%) and CD19+ (8%). The adequate ALC recovery was associated with age < 8 years, bone marrow grafts, myeloablative conditioning, non-use of serotherapy and non-haploidentical donors. The ALC and CD3+CD8+ on D+100 counts were higher in patients with the cytomegalovirus infection. The CD3+CD4+ recovery was associated with an age < 8 years, a non-malignant disease and a lower incidence of acute graft-versus-host disease ≥ grade 2. Furthermore, the ALC recovery on D+100 resulted in a higher overall survival, regardless of the disease type (HR 3.65, 1.05 - 12.71, p = 0.04). CONCLUSION: Several factors influenced the IR after the allo-HSCT. The ALC ≥ 500/µL on D+100 was a simple IR predictor of survival, easily available to resource-limited centers.

Saprochaete clavata invasive infection: characterization, antifungal susceptibility, and biofilm evaluation of a rare yeast isolated in Brazil

ABSTRACT Rare emerging pathogens such as Saprochaete clavata are associated with invasive fungal diseases, high morbidity, mortality, rapidly fatal infections, and outbreaks. However, little is known about S. clavata infections, epidemiology, risk factors, treatment, biofilms, and disease outcomes. The objective of this study was to describe a new case of severe S. clavata infection in a patient diagnosed at a referral children's hospital in Brazil, including antifungal minimal inhibitory concentration, S. clavata biofilm characterization, and molecular characterization. The S. clavata isolated from an immunocompromised 11-year-old male patient was characterized using MALDI-TOF, Gram staining, scanning electron microscopy (SEM), and next generation sequencing (NGS) of genomic DNA. Biofilm production was also evaluated in parallel with determining minimal inhibitory concentration (MIC) and biofilm sensitivity to antifungal treatment. We observed small to medium, whitish, farinose, dry, filamentous margin colonies, yeast-like cells with bacillary features, and biofilm formation. The MALDI-TOF system yielded a score of ≥ 2,000, while NGS confirmed S. clavata presence at the nucleotide level. The MIC values (in mg L-1) for tested drugs were as follows: fluconazole = 2, voriconazole ≤ 2, caspofungin ≥ 8, micafungin = 2, amphotericin B = 4, flucytosine ≤ 1, and anidulafungin = 1. Amphotericin B can be active against S. clavata biofilm and the fungus can be susceptible to new azoles. These findings were helpful for understanding the development of novel treatments for S. clavata-induced disease, including combined therapy for biofilm-associated infections.

Immune reconstitution after allogenic stem cell transplantation: An observational study in pediatric patients

Abstract Introduction The immune reconstitution (IR) after the allogenic hematopoietic stem cell transplantation (allo-HSCT) is a progressive process intrinsically correlated to the therapeutic success. It is essential to understand the interfering factors in IR to prevent the HSCT-related mortality. Methods We retrospectively evaluated the clinical outcomes, absolute lymphocyte counts (ALCs) and lymphocyte subtypes at different time-points of 111 pediatric patients with allogeneic HSCT for malignant and non-malignant diseases from 2013 to 2018. Results The ALCs gradually increased on D+30, D+100, and D+180 (medians 634/μL, 1022/μL and 1541/μL, respectively). On D+100, the CD3+CD8+ achieved the highest recovery rate (68%), followed by the CD16+CD56+ (47%), CD3+CD4+ (39%) and CD19+ (8%). The adequate ALC recovery was associated with age < 8 years, bone marrow grafts, myeloablative conditioning, non-use of serotherapy and non-haploidentical donors. The ALC and CD3+CD8+ on D+100 counts were higher in patients with the cytomegalovirus infection. The CD3+CD4+ recovery was associated with an age < 8 years, a non-malignant disease and a lower incidence of acute graft-versus-host disease ≥ grade 2. Furthermore, the ALC recovery on D+100 resulted in a higher overall survival, regardless of the disease type (HR 3.65, 1.05 - 12.71, p= 0.04). Conclusion Several factors influenced the IR after the allo-HSCT. The ALC ≥ 500/μL on D+100 was a simple IR predictor of survival, easily available to resource-limited centers.

WAITING LIST FOR LIVER TRANSPLANTATION: CLINICAL AND ECONOMIC BURDEN.

BACKGROUND: Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). OBJECTIVE: To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. METHODS: The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. RESULTS: The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). CONCLUSION: The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.

Genotypic Diversity of Candida parapsilosis Complex in Invasive Candidiasis at a Pediatric Tertiary Hospital: A 5-Year Retrospective Study.

Invasive candidiasis (IC) contributes to the morbidity and mortality of hospitalized patients and represents a significant burden to the healthcare system. Previous Brazilian studies have reported the presence of endemic Candida parapsilosis sensu stricto genotypes causing candidemia and clonal transmission involving fluconazole-resistant isolates. We performed a 5-year retrospective analysis of IC cases in a Brazilian tertiary pediatric hospital and conducted a molecular investigation of C. parapsilosis sensu stricto. Non-duplicate C. parapsilosis sensu stricto genotyping was performed by microsatellite analysis. Antifungal susceptibility and biofilm formation were also evaluated. A total of 123 IC episodes were identified, with an IC incidence of 1.24 cases per 1000 hospital admissions and an overall mortality of 34%. The main species were the C. parapsilosis complex (35.8%), Candida albicans (29.2%), and Candida tropicalis (21.9%). All C. parapsilosis sensu stricto were recovered from blood cultures, and 97.5% were biofilm producers. Microsatellite typing identified high genotypic diversity among the isolates. We observed that all isolates were sensitive to amphotericin B, and although one isolate was non-sensitive to fluconazole, only a silent mutation on ERG11 gene was identified. No clear evidence of clonal outbreak or emergence of fluconazole-resistant isolates was found, suggesting that multiple sources may be involved in the epidemiology of IC in children.

Lista de espera para transplante hepático: impacto clínico e econômico / Waiting list for liver transplantation: clinical and economic burden

ABSTRACT Background Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). Objective: To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. Methods The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. Results: The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). Conclusion: The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.

RESUMO Contexto O impacto da doença é um indicador relacionado ao estado de saúde. Dados epidemiológicos norte-americanos e europeus mostraram que, nas últimas décadas, o impacto da doença hepática crônica tem aumentado significativamente. Não há estudos que avaliem o impacto das descompensações da doença hepática crônica na lista de espera para transplante hepático (TxH) com doador falecido. Objetivo: Determinar o impacto clínico e econômico das descompensações da doença hepática nos pacientes em lista de espera sob a perspectiva do centro transplantador. Métodos Foram analisados, retrospectivamente, os prontuários de 104 pacientes incluídos em lista de espera para TxH com doador falecido entre outubro de 2012 e maio de 2016 e acompanhados integralmente no centro transplantador. Dados clínicos foram obtidos do prontuário eletrônico, enquanto dados econômicos foram coletados através de software de gestão hospitalar. A apropriação dos custos médicos diretos foi realizada sob duas metodologias: custeio por absorção pleno e microcusteio. Resultados: A descompensação com maior incidência foi a ascite refratária (20,2%) seguida de encefalopatia portossistêmica (12,5%). A média de internações por paciente foi de 1,37±3,42. A hemorragia digestiva alta varicosa foi a descompensação com maior tempo mediano de internação (18 dias), seguida da síndrome hepatorrenal (13,5 dias). A descompensação mais onerosa foi a síndrome hepatorrenal (custo médio de US$ 3.565), seguida encefalopatia portossistêmica (US$ 2.576) e a hemorragia digestiva alta varicosa (US$ 1.530). Conclusão O impacto da doença hepática crônica inclui um custo importante para os sistemas de saúde. Além disso, é provável que seja ainda maior em decorrência do curso insidioso da doença.

Risk of acute kidney injury and cost-effectiveness analysis comparing vancomycin and linezolid for the treatment of pediatric patients infected with Gram-positive bacteria / Risco de lesão renal aguda e custo-efetividade comparando vancomicina e linezolida para o tratamento de pacientes pediátricos infectados por bactérias Gram-positivas

Objective: This study aimed to compare the occurrence of acute kidney injury (AKI) in pediatric patients who used vancomycin (VAN) or linezolid (LNZ) to treat Gram-positive coccus (GPC) infections and to assess which treatment (VAN or LNZ) is the most cost-effective considering a pediatric hospital perspective. Methods: A retrospective cohort was performed to evaluate the occurrence of nephrotoxicity in pediatric patients without previous AKI, with GPC infections that used LNZ, or VAN monitored by serum VAN levels. Initially, descriptive analysis and Fisher and chisquare test were performed for this comparison. Then, a cost-effectiveness analysis was conducted through a decision tree model. The outcomes of interest were the rate of AKI related to the drug and the rate of admission to the intensive care unit (ICU) and cure. Results: In patients without previous acute kidney injury (AKI), 20% developed nephrotoxicity associated with VAN versus 9.6% in the LNZ group (p = 0.241). As there was no difference in nephrotoxicity between VAN andlinezolid (LNZ), vancomycin (VAN) monitored by serum VAN levels can optimize and rationalize the treatment. The nephrotoxicity risk criterion should not guide the prescription for LNZ. Furthermore, the average global cost of treatment with VAN was approximately R$ 43,000, while for LNZ, it was R$ 71,000. Conclusion: VAN was considered dominant (lower cost and greater effectiveness) over LNZ for treating patients with GPC infection.

Objetivo: Este estudo objetivou comparar a ocorrência de lesão renal aguda (LRA) em pacientes pediátricos que usaram vancomicina (VAN) ou linezolida (LNZ) para tratar infecções por cocos Gram-positivos (CGP) e avaliar qual tratamento (VAN ou LNZ) é o mais custo-efetivo considerando a perspectiva de um hospital pediátrico. Métodos: Foi realizada uma coorte retrospectiva para avaliar a ocorrência de nefrotoxicidade em pacientes pediátricos sem LRA prévia, com infecções por CGP que utilizaram LNZ ou VAN, combinada com vancocinemia. Para essa comparação, inicialmente foram realizados análise descritiva e testes de Fisher e qui-quadrado. Em seguida, foi realizada uma análise de custo-efetividade por meio de um modelo de árvore de decisão. Os desfechos de interesse foram a taxa de LRA relacionada ao medicamento e a taxa de internação em unidade de terapia intensiva e cura. Resultados: Nos pacientes sem LRA prévia, 20% deles desenvolveram nefrotoxicidade associada à VAN versus 9,6% no grupo LNZ (p = 0,241). Como não houve diferença na nefrotoxicidade entre VAN e LNZ, a VAN combinada com a vancocinemia pode otimizar e racionalizar o tratamento, e a prescrição de LNZ não deve ser guiada pelo critério de risco de nefrotoxicidade. Além disso, o custo médio global do tratamento com VAN foi de aproximadamente R$ 43.000, enquanto para LNZ foi de R$ 71.000. Conclusão: Assim, a VAN foi considerada dominante (menor custo e maior eficácia) sobre a LNZ para o tratamento de pacientes com infecção por CGP.

Amphotericin B in Pediatrics: Analysis by Age Stratification Suggests a Greater Chance of Adverse Events from 13 Months of Age Onwards.

BACKGROUND AND OBJECTIVE: Amphotericin B deoxycholate (AMB-D) remains an antifungal agent with great therapeutic value in pediatric patients. The currrent consensus is that its use in neonates is safer than in older children. However, childhood presents different periods of development that deserve to be evaluated more precisely. Our goal was to assess the usage profile of AMB-D in stratified pediatric age groups, adapted according to the National Institute of Child Health and Human Development classification. METHODS: This retrospective cross-sectional observational study was conducted at a Brazilian tertiary children's hospital between January 2014 and December 2019.  Data of patients who received at least two doses of intravenous AMB-D while hospitalized were extracted from electronic health files. Information on patient demographics, underlying diseases and comorbidities, laboratory examinations, fungal infection diagnosis, and AMB-D use were gathered following specific criteria. Nonparametric tests were applied, such as the chi-square test to compare proportions and Fisher's exact test to assess the association between categorical variables or contingency tables. RESULTS: One hundred and twenty-seven (127) medical records were stratified as preterm neonatal (birth <37 weeks postmenstrual age), term neonatal (birth-27 days), infants (28 days-12 months), toddlers (13 months-2 years), early childhood (3-5 years), middle childhood (6-11 years), and early adolescence (12-18 years). The criteria for the indication of AMB-D followed empirical use as the main indication (n = 74; 58.26%), proven and probable fungal infection (n = 39; 30.71%), and medical suspicion (n = 14; 11.02%). Candida spp. was the main etiologic agent isolated in cultures, with the highest frequency of C. albicans (n = 18; 40%), followed by Candida parapsilosis (n = 14; 31.11%), and Candida tropicalis (n = 6; 13.33%). Very few acute infusion-related adverse effects were observed during the administration of AMB-D in pediatric patients. We found an unfavorable impact of AMB-D use in patients from 13 months of age onwards suggesting this group as a turning point for a greater chance of adverse events, and not soon after the neonatal period. CONCLUSIONS: Clinical or observational studies based on age stratification are essential to accurately elucidate whether potentially toxic drugs can be used safely in the pediatric population. Our search for a turning point was shown to contribute to the accuracy of the study, as it provided data on the impact of D-AMB in specific pediatric age groups.