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Objectives To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients. Methods Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed. Results MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24–2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea. Conclusions DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.

As neutropenic patients with haematological cancer are not typically included in randomized controlled trials (RCTs) of candidaemia, there is low quality of evidence regarding the management of this common opportunistic mycosis in this patient population, which is at high risk for poor outcomes. Herein we identify the gaps in knowledge that are not addressed by the modern RCTs and candidaemia guidelines, and outline some considerations for the future clinical research agenda in candidaemia/invasive candidiasis in haematological patients.

Background The clinical relevance and the potential prognostic role of persistently negative (1,3)-β-D-glucan (BDG) in adults with proven candidemia is unknown. Methods This retrospective study included all adults diagnosed with candidemia our tertiary university hospital from 2012–2017 who had at least 2 serum BDG determinations throughout the episode of fungemia (Fungitell Assay; positive cut-off ≥80pg/mL). Epidemiology and clinical outcomes were compared between patients with all negative versus any positive BDG tests. Poor clinical outcomes included complications due to candidemia or 30-day all-cause mortality. Results Overall, 26/148 (17.6%) candidemic adults had persistently negative BDG tests. These patients were less likely to present Candida growth in all 3 sets of blood cultures (15.4% vs 45.1%; P = .005) and had less severe clinical presentations (median Pitt score, 0 [interquartile range {IQR} 0–1] vs 1 [IQR 0–2] in patients with any positive BDG test; P = .039). Although adequate treatment was equally provided to both groups (96.2% in persistently negative group vs 93.4 in positive group; P = .599), the persistently negative group had a higher rate of microbiological clearance in the first follow-up blood cultures (92.3% vs 69.7% in positive group; P = .005), fewer complications due to candidemia (7.7% vs 33.6% in positive group; P = .008), a lower 30-day mortality rate (3.8% vs 23.8% in positive group; P = .004), and a shorter in-hospital stay (34 days [IQR 18–55] vs 51 days [IQR 35–91] in positive group; P = .003). In the multivariate analysis, persistently negative BDG tests were independently associated with better prognoses (odds ratio 0.12, 95% confidence interval 0.03–0.49; P = .003). Conclusions Candidemic patients with persistently negative BDG tests present a better prognosis than the comparative group, probably due to a lower systemic fungal burden. In this context, the appropriate use of persistently negative BDG results could be an aid to individualize therapeutic management in the near future.

The implementation of 1,3 &beta, d-glucan (BDG) has been proposed as a diagnostic tool in antifungal stewardship programs (ASPs). We aimed to analyze the influence of serum BDG in an ASP for oncologic patients and solid organ transplant (SOT) recipients. We conducted a pre&ndash, post study. In the initial period (PRE), the ASP was based on bedside advice, and this was complemented with BDG in the post-period (POST). Performance parameters of the BDG assay were determined. Antifungal (AF) use adequacy was evaluated using a point score. Clinical outcomes and AF costs were also compared before and after the intervention. Overall, 85 patients were included in the PRE-period and 112 in the POST-period. Probable or proven fungal infections were similar in both groups (54.1% vs. 57.1%, p = 0.67). The determination of BDG contributed to improved management in 75 of 112 patients (66.9%). The AF adequacy score improved in the POST-period (mean 7.75 vs. 9.29, p &lt, 0.001). Median days of empiric AF treatment was reduced in the POST-period (9 vs. 5 days, p = 0.04). All-cause mortality (44.7% vs. 34.8%, p = 0.16) was similar in both periods. The cost of AF treatments was reduced in the POST-period with a difference of 779.6 &euro, /patient. Our data suggest that the use of BDG was a cost-effective strategy that contributed to safely improving the results of an ASP for SOT and oncologic patients.

Summary: Background: Mortality rates among adults with candidemia vary widely in different geographical settings. Studies directly comparing epidemiology and clinical practices between countries are scarce and could bring insights into improving clinical outcomes. Methods: Retrospective cohort including adults with candidemia diagnosed in five tertiary hospitals from Brazil and Spain between 2010-2018. Adequate therapeutic management included appropriate antifungal therapy and central-venous-catheter (CVC) removal within 48 h of fungemia. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors associated with 30-day mortality. Findings: Overall, 720 patients were included, being 323 from Spain. Spanish patients received echinocandins more often (52·5% vs. 39·3%, p = 0.001), initiated antifungals earlier [2 (0-7) vs. 2 days (0-16), p1 [OR 2·56, 95%CI (1·776-3·690), p

Objectives The role of biofilm production in the outcome of candidaemia remains under discussion. Current evidence relies on variable biofilm detection methods while evaluating distinct clinical end points. We aimed to determine the impact of biofilm production measured by metabolic activity (MA) and biomass (BM) on the prognosis of adults with candidaemia. Methods Retrospective cohort including 280 adults with candidaemia admitted from 2010 to 2016. BM was assessed using crystal violet binding stain and the XTT reduction assay was used to detect MA. Strains were classified as high and moderate-low biofilm producers according to published cut-offs. The primary outcome was overall mortality within 7 and 30 days. The secondary outcome was unfavourable prognosis defined as metastatic infection, admission to an intensive care unit due to the severity of candidaemia, or death within 30 days. Results High BM and high MA were detected in 90 (32.1%) and 114 (40.7%) of the 280 isolates, respectively. Comparison of high and moderate-low biofilm forming isolates revealed no correlation between biofilm production and 7-day mortality (BM high 15/90 (16.7%) versus moderate-low 24/190 (12.6%); MA high 12/114 (10.5%) versus moderate-low 27/166 (16.3%)), 30-day mortality (BM high 34/90 (37.8%) versus moderate-low 61/190 (32.1%); MA high 33/114 (28.9%) versus moderate-low 62/166 (37.3%)), or unfavourable prognosis (BM high 45/90 (50.0%) versus moderate-low 73/190 (38.4%); MA high 41/114 (36.0%) versus moderate-low 77/166 (46.4%)). Conclusions Biofilm production was not a predictor of mortality or of unfavourable prognosis in adults with candidaemia.

We report the first case of disseminated infection by Gymnascella hyalinospora in a solid organ transplant recipient. This case highlights the role of low-virulence environmental molds as an emerging cause of breakthrough invasive fungal infection in immunocompromised hosts. Nosocomial strategies of infection control including antimicrobial stewardship and advances on fast diagnostic methods are strongly encouraged to improve patient prognosis.

To investigate the causes and the clinical significance of persistent candidemia (PC) in adults diagnosed in a tertiary hospital with an active antifungal stewardship program. Retrospective cohort including all adults with candidemia from 2010 to 2018. PC was defined as any positive follow-up blood culture (BC) obtained ≥ 5 days from the first BCs yielding the same Candida species. PC was detected in 35/255 (13.7%) patients. There were no differences regarding antifungal adequacy in PC vs. non-PC (94.3% vs. 82.3%, p = 0.084) and primary source control (63.3% vs. 76.4%, p = 0.172) at the time of the follow-up BCs. The average time until source control (2 [0-37] vs. 2 days [0-44], p = 0.311) or adequate antifungal treatment (2 [0-26] vs. 2 days [- 2-10], p = 0.748) was similar. Patients with PC had more non-ocular complications (31.4% vs. 10.5%, p = 0.002). No impact on 30-day mortality was observed (31.4% vs. 22.3%, p = 0.238). The only independent factor associated with PC was to have a previously undetected site of infection [OR 4.28, 95%CI (1.77-10.34), p = 0.001]. Persistent candidemia was not associated with inadequate or delayed therapeutic management, nor higher 30-day mortality rates. Timely screening and control of unexpected infection sources are encouraged to shorten hospitalization and improve patient care.

The high rates of antifungal resistance in Candida glabrata may be facilitated by the presence of alterations in the MSH2 gene. We aimed to study the sequence of the MSH2 gene in 124 invasive C. glabrata isolates causing incident episodes of candidemia (n = 81), subsequent candidemia episodes (n = 9), endocarditis (n = 2), and in vitro-generated echinocandin-resistant isolates (n = 32) and assessed its relationship with genotypes, acquisition of antifungal resistance in vivo and in vitro, and patient prognosis. The MSH2 gene was sequenced, and isolates were genotyped using six microsatellite markers and multilocus sequence typing (MLST) based on six housekeeping genes. According to EUCAST, isolates causing candidemia (n = 90) were echinocandin susceptible, and four of them were fluconazole resistant (MIC ≥64 mg/liter). One isolate obtained from a heart valve was resistant to micafungin and anidulafungin (MICs, 2 mg/liter and 1 mg/liter, respectively). MSH2 gene mutations were present in 44.4% of the incident isolates, the most common being V239L. The presence of MSH2 mutations was not correlated with in vitro or in vivo antifungal resistance. Microsatellite and MLST revealed 27 genotypes and 17 sequence types, respectively. Fluconazole-resistant isolates were unrelated. Most MSH2 mutations were found in cluster isolates; conversely, some mutations were found in more than one genotype. No clinical differences, including previous antifungal use, were found between patients infected by wild-type MSH2 gene isolates and isolates with any point mutation. The presence of MSH2 gene mutations in C. glabrata isolates causing candidemia is not correlated with specific genotypes, the promotion of antifungal resistance, or the clinical outcome.

BACKGROUND: Esophageal trauma is considered one of the most severe lesions of the digestive tract. There is still much controversy in choosing the best treatment for cases of esophageal perforation since that decision involves many variables. The readiness of medical care, the patient's clinical status, the local conditions of the perforated segment, and the severity of the associated injuries must be considered for the most adequate therapeutic choice. AIM: To demonstrate and to analyze the results of urgent esophagectomy in a series of patients with esophageal perforation. METHODS: A retrospective study of 31 patients with confirmed esophageal perforation. Most injuries were due to endoscopic dilatation of benign esophageal disorders, which had evolved with stenosis. The diagnosis of perforation was based on clinical parameters, laboratory tests, and endoscopic images. The main surgical technique used was transmediastinal esophagectomy followed by reconstruction of the digestive tract in a second surgical procedure. Patients were evaluated for the development of systemic and local complications, especially for the dehiscence or stricture of the anastomosis of the cervical esophagus with either the stomach or the transposed colon. RESULTS: Early postoperative evaluation showed a survival rate of 77.1% in relation to the proposed surgery, and 45% of these patients presented no further complications. The other patients had one or more complications, being pulmonary infection and anastomotic fistula the most frequent. The seven patients (22.9%) who underwent esophageal resection 48 hours after the diagnosis died of sepsis. At medium and long-term assessments, most patients reported a good quality of life and full satisfaction regarding the surgery outcomes. CONCLUSIONS: Despite the morbidity, emergency esophagectomy has its validity, especially in well indicated cases of esophageal perforation subsequent to endoscopic dilation for benign strictures. RACIONAL: O trauma de esôfago é considerado uma das lesões mais graves do trato digestivo. O tratamento de escolha para casos de perfuração esofágica ainda é controverso, visto que esta decisão envolve inúmeras variáveis. As condições clínicas do paciente, as condições locais no segmento do esôfago perfurado, a gravidade das lesões associadas e o tempo de atendimento são essenciais para que a equipe cirúrgica possa instituir o tratamento adequado. OBJETIVO: Demonstrar e analisar os resultados da esofagectomia de urgência em uma série de pacientes com perfuração do esôfago. MÉTODO: Estudo retrospectivo incluindo 31 pacientes com confirmação diagnóstica de perfuração esofágica. A maior parte das lesões foi consequente à dilatação endoscópica de afecções benignas do esôfago que evoluíram com estenose. O diagnóstico da perfuração foi baseado em parâmetros clínicos, exames laboratoriais, radiológicos e endoscopia digestiva alta. A principal técnica cirúrgica utilizada foi a esofagectomia transmediastinal seguida da reconstrução do trânsito digestivo em um segundo tempo cirúrgico. Os pacientes foram avaliados em relação ao desenvolvimento de complicações sistêmicas e locais, notadamente deiscência e estenose da anastomose do esôfago cervical com o estômago ou cólon transposto. RESULTADOS: A avaliação pós-operatória precoce demonstrou sobrevida de 77,1% em relação ao ato cirúrgico proposto, sendo que 45% não apresentou qualquer complicação. Os outros pacientes apresentaram uma ou mais complicações, sendo a infecção pulmonar e a fístula anastomótica as mais frequentes. Sete pacientes (22,9%) evoluíram a óbito por quadro séptico. Tais pacientes foram submetidos à ressecção esofágica após 48 horas do diagnóstico da perfuração. Na avaliação a médio e longo prazo, a maioria dos pacientes relatou estar satisfeito com o ato cirúrgico, referindo boa qualidade de vida. CONCLUSÕES: Apesar da morbidade não desprezível, a esofagectomia de urgência tem sua validade, principalmente em casos de perfuração esofágica consequentes à dilatação endoscópica para estenoses benignas.

To evaluate the secular trend of menarche according to body mass index (BMI).Six hundred and eighty five girls (7-18 years) assessed in 2001 were compared with 750 evaluated in 2010. They were grouped by BMI Z-score: (thin + normal) and (overweight + obese). Menarche was reported by status quo and age at menarche estimated by a logit model. We used the Qui-square test, Mann-Whitney test, and Logistic Regression, at a 5% significance level.Menarche advanced 3.24 months. There was an increase in obesity, and a decrease of the prevalence of normal girls. Menarche was anticipated by 1.44 month in the thin + normal group and by 5.76 months in the overweight + obese group. There was no interaction between the effects determined by the evaluated period and nutritional diagnosis.Although both the period and BMI influence the menarche, one cannot attribute this advance only to changes in the nutritional profile of the sample. Other factors that were not tested may also contribute to this finding.

OBJETIVO: Avaliar a tendência secular da menarca de acordo com o índice de massa corporal (IMC). SUJEITOS E MÉTODOS: Seiscentos e oitenta e cinco meninas (7-18 anos) avaliadas em 2001 foram comparadas a 750 avaliadas em 2010. Elas foram agrupadas pelo Z-escore do IMC em: (magreza + eutrofia) e (sobrepeso + obesidade). A menarca foi relatada pelo status quo e a idade, estimada pelo logito. Foram utilizados os testes Qui-quadrado, Mann-Whitney e a Regressão logística, com significância de 5%. RESULTADOS: A menarca adiantou 3,24 meses entre 2001 e 2010. Houve aumento da obesidade e diminuição de eutróficas. O evento antecipou 1,44 mês no grupo magreza + eutrofia e 5,76 meses no sobrepeso + obesidade. Não houve interação entre os efeitos determinados pelo período avaliado e diagnóstico nutricional. CONCLUSÕES: Embora tanto o período quanto o IMC tenham influenciado a menarca, não se pode atribuir essa antecipação só à mudança do perfil nutricional da amostra. Outros fatores não testados podem estar contribuindo também para isso. OBJECTIVE: To evaluate the secular trend of menarche according to body mass index (BMI). SUBJECTS AND METHODS: Six hundred and eighty five girls (7-18 years) assessed in 2001 were compared with 750 evaluated in 2010. They were grouped by BMI Z-score: (thin + normal) and (overweight + obese). Menarche was reported by status quo and age at menarche estimated by a logit model. We used the Qui-square test, Mann-Whitney test, and Logistic Regression, at a 5% significance level. RESULTS: Menarche advanced 3.24 months. There was an increase in obesity, and a decrease of the prevalence of normal girls. Menarche was anticipated by 1.44 month in the thin + normal group and by 5.76 months in the overweight + obese group. There was no interaction between the effects determined by the evaluated period and nutritional diagnosis. CONCLUSIONS: Although both the period and BMI influence the menarche, one cannot attribute this advance only to changes in the nutritional profile of the sample. Other factors that were not tested may also contribute to this finding. Pontifícia Universidade Católica de Campinas (PUC-Campinas) Faculdade de Medicina Universidade Estadual de Campinas (Unicamp) Faculdade de Ciências Médicas Departamento de Pediatria Universidade Federal de São Paulo (UNIFESP) UNIFESP, EPM SciELO

Introduction Lipomas of the gastrointestinal tract are a rare condition. Only 5% are of gastric origin, and this corresponds to 2% to 3% of all benign tumors of the stomach and less than 1% of all gastric neoplasms. It is our purpose to report an unusual presentation of a giant gastric lipoma in an oligosymptomatic patient and highlight the importance of discussing differential diagnosis in this situation. A review of the literature has shown that this is one of the largest gastric lipomas described. Case presentation We describe a rare case of a benign gastric tumor with uncommon features in a 63-year-old Caucasian woman. She was admitted with abdominal discomfort, nausea, and upper abdominal fullness after eating. The lesion was suspicious of malignancy because of its dimension and central contrast enhancement on computed tomography. Conventional upper digestive endoscopy revealed a large bulging mass in the gastric posterior wall and three ulcerated areas. In this procedure, a technical limitation due to the location of the mass in the submucosa prevented an adequate biopsy from being obtained. The fragments obtained from the ulcers revealed nothing but necrotic mucosa. Our patient underwent a subtotal gastrectomy and D1 lymphadenectomy with a Roux-en-Y reconstruction. Macroscopic findings revealed a 12 × 8 × 6cm mass with a volume of 576cm3, and the histological pattern demonstrated well-differentiated mature adipose tissue surrounded by a fibrous capsule, confirming the diagnosis of gastric submucosal lipoma. Conclusions Gastric lipoma is a rare benign disease that eventually simulates a malignant tumor.