Gastric inflammatory myofibroblastic tumor, a rare mesenchymal neoplasm: A case report.

BACKGROUND: The inflammatory myofibroblastic tumor (IMT) is a rare mesenquimal tumor of doubtful biological behaviour. It's characterised for affecting mainly children and young adults, although it can appear at any age, being the lungs the primary affected organ (in children it represents 20% of all primary pulmonary tumors). CASE SUMMARY: We present the case of a 45 year old woman, with a computed tomography (CT) finding of injury on the anterior surface of the fundus/gastric body and a solid perigastric injury of 12 mm in the ecoendoscopy. The case is presented in the tumor committee deciding to perform a laparoscopic wedge resection. The histological diagnosis was a IMT. The diagnosis is based on imaging tests like the abdominal CT, abdominal ecography and the ecoendoscopy but to confirm the diagnosis a pathological study is necessary. CONCLUSION: Due to the unpredictable nature of this tumor, surgical resection is the best therapeutic option.

Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence of Clostridioides difficile infection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial.

INTRODUCTION: Clostridioides difficile infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT. METHODS AND ANALYSIS: We will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital '12 de Octubre' (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: NCT05320068.

Determining the usefulness of systematic 18F-FDG PET/CT for the management of invasive fungal infection (PETIFI project): a prospective national multicentre cohort study protocol.

INTRODUCTION: The evaluation of staging and activity of invasive fungal infection (IFI) is used to adjust the type and duration of antifungal therapy (AT). Typically anatomy-based imaging is used. Positron emission tomography/CT with 18F-fluorodeoxyglucose (18F-FDG PET/CT) not only evaluates more than one body area in one session, but adds functional information to the anatomic data provided by usual imaging techniques and can potentially improve staging of IFI and monitoring of the response to therapy. Our objective is to analyse the impact of the systematic use of 18F-FDG PET/CT in IFI diagnostic and therapeutic management. METHODS AND ANALYSIS: Multicentre prospective cohort study of IFI with performance of systematic 18F-FDG PET/CT at diagnosis and follow-up that will be carried out in 14 Spanish tertiary hospitals. It is planned to include 224 patients with IFI over a 2-year study period. Findings and changes in management before and after 18F-FDG PET/CT will be compared. Additionally, the association of initial quantitative 18F-FDG PET/CT parameters with response to therapy will be evaluated.The primary endpoint is to compare the yield of 18F-FDG PET/CT with standard management without 18F-FDG PET/CT in IFI at initial assessment (staging) and in monitoring the response to treatment.The impact of the results of 18F-FDG PET/CT on the diagnostic-therapeutic management of patients with IFI (added value), as well as the prognostic ability of different quantification parameters of 18F-FDG PET/CT will be secondary endpoints. ETHICS AND DISSEMINATION: The Clinical Research Ethics Committee of Puerta de Hierro-Majadahonda University Hospital approved the protocol of the study at the primary site. We plan to publish the results in high-impact journals. TRIAL REGISTRATION NUMBER: NCT05688592.

[High frequency of endoluminal thrombus in patients with ischaemic stroke following COVID-19]. / Alta Frecuencia de Trombo Endoluminal en pacientes con ictus isquémico tras la infección por Coronavirus 2019.

BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection.Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with COVID-19 who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack).Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%).We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.

A retrospective validation of different scores of guideline adherence and infectious diseases consultation on candidaemia: The higher, the better.

BACKGROUND: Recently, several scores to quantify compliance with the guidelines in candidaemia management (EQUAL, GEMICOMED, Valerio) have been developed. Evidence supporting the association of these scores to the prognosis is scarce. We aim to evaluate the performance of these candidaemia guideline adherence scores to predict candidaemia outcome. METHODS: We recorded retrospectively data from candidaemia episodes (January 2017-December 2018). We analysed adherence to guidelines for candidaemia management according to EQUAL, GEMICOMED and Valerio scores, and we correlated those to outcome. RESULTS: Fifty-four first episodes of candidaemia were retrieved. Five patients who died in the first 48 hours after blood cultures were not included. Thirty-day mortality in evaluable patients was 18.4%. Median adherence to guidelines according to EQUAL score was 17 (interquartile range [IQR]: 15-19), and according to GEMICOMED was 86% (IQR: 72.5%-100%). According to Valerio score, adequacy of antifungal prescription was 8.5/10 (SD: 1.9). A cut-off of ≥17 for EQUAL or compliance >70% for GEMICOMED was associated with inferior 30-day mortality (7.1% vs 33.3%, P = .028 and 7.9% vs 54.5%, P = .002, respectively). Infectious diseases (ID) evaluated cases obtained a better EQUAL score (>17; 82.1% vs 42.9%, P = .006), had inferior 30-day mortality (9.4% vs 35.3%, P = .049) and a better antifungal prescription adequacy (Valerio score 9.0 vs 7.5, P = .011). CONCLUSION: Adherence to guidelines for candidaemia management evaluated by means of EQUAL and GEMICOMED score was associated with a decreased 30-day mortality. Adequacy of antifungal prescription can be ameliorated. ID consultation improved guideline adherence and was associated with decreased 30-day mortality.

Sarilumab versus standard of care for the early treatment of COVID-19 pneumonia in hospitalized patients: SARTRE: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: In some patients, acute, life-threatening respiratory injury produced by viruses such as SARS-CoV and other viral pneumonia are associated with an over-exuberant cytokine release. Elevated levels of blood IL-6 had been identified as a one of the risk factors associated with severe COVID-19 disease. Anti-IL6 inhibitors are among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients. At present, their use is prioritized to patients with severe interstitial pneumonia (Brescia-COVID Scale-COVID 2-3) with hyperinflammation as determined by the presence of elevated IL6 and/or d-dimer, or progressive d-dimer increase, in patients who otherwise are subsidiary to ICU admission. However, many uncertainties remain on the actual role of anti-IL6 inhibitors in this setting, and whether current use and timing is the right one. There is the hypothesis that the use of anti-IL6 inhibitors at an earlier state during the hyperinflammatory syndrome would be beneficial and may avoid progressing to ARDS. On the other hand, the standard of care has changed and nowadays the use of corticosteroids has become part of the SOC in the treatment of COVID-19 pneumonia. Our limited experience suggests that better treatment outcomes can be achieved when combining IL6-inhibitors (e.g. sarilumab) with corticosteroids. The aim of the present study is to evaluate if an earlier therapeutic intervention with sarilumab plus SOC (including corticosteroids) may be more effective than current standard of care alone, in preventing progression to respiratory failure in COVID-19 infected patients with interstitial pneumonia. This study will also provide supportive evidence to that provided by currently ongoing studies on the efficacy and safety of sarilumab in this clinical context. TRIAL DESIGN: A phase two multi-center randomised controlled trial (RCT) with two parallel arms (1:1 ratio). PARTICIPANTS: They will be hospitalized patients, of at least 18 years of age, with severe COVID-19 who have positive RT-PCR test and have radiographic evidence of pulmonary infiltrates by imaging or rales/crackles on exam and SpO2 ≤ 94% on room air that requires supplemental oxygen. Patients must present elevation of inflammatory parameters (IL-6 > 40 pg/mL or d-dimer >1.0 mcg/ml) or, alternatively, progressive worsening in at least two of these inflammatory parameters in the prior 24-48h: CRP, LDH, serum ferritin, lymphopenia, or d-dimer. EXCLUSION CRITERIA: high oxygen requirements (including face mask with reservoir, non-invasive mechanical ventilation or high flow nasal cannula, or mechanical ventilation), admission to ICU, pregnancy or lactation, allergy or hypersensitivity to sarilumab or corticoesteroids, immunosuppressive antibody therapy within the past 5 months, AST/ALT values > 10 x ULN, neutropenia (< 0.5 x 109/L), severe thrombocytopenia (< 50 x 109/L), sepsis caused by an alternative pathogen, diverticulitis with risk of perforation or ongoing infectious dermatitis. The study will be conducted in several hospitals in Spain. INTERVENTION AND COMPARATOR: Patients randomised to the experimental arm will receive sarilumab + methylprednisolone plus SOC for COVID-19. Patients included in the control arm will receive methylprednisolone plus SOC for COVID-19. Corticosteroids will be given to all patients at a 1mg/kg/d of methylprednisolone for at least 3 days. Clinical follow-up visits will be performed at 3, 5, and 15 days after treatment randomization. Patients in the control group (SOC group without sarilumab) progressing to Brescia- COVID 2-3 plus inflammatory markers, will be given the option to be rescued with sarilumab at the same doses and, in that case, be included in an open-label phase and be followed up for additional weeks (with visits at 3, 7 and 15 days after sarilumab rescue administration). Patients randomly assigned to sarilumab therapy at baseline progressing to Brescia-COVID 2-3 will be rescued according to local clinical practice protocols. A final follow-up visit will be conducted for all patients at day 29 from randomization, regardless of initial treatment assignment. MAIN OUTCOMES: Primary end point is the proportion of patients progressing to either severe respiratory failure (Brescia-COVID ≥2), ICU admission, or death. RANDOMIZATION: Randomization codes were produced by means of the PROC PLAN of the SAS system, with a 1:1 assignment ratio, stratifying by centre and using blocks multiple of 2 elements. The randomization schedule will be managed through the eCRF in a concealed manner. BLINDING (MASKING): All study drugs will be administered as open label. No blinding methods will be used in this trial. NUMBERS TO BE RANDOMISED (SIMPLE SIZE): The target sample size will be 200 COVID-19 patients, who will be allocated randomly to control arm (100) and treatment arm (100). TRIAL STATUS: Protocol Code: SARTRE Protocol Date: May 05th 2020. Version: 2.0 The study has been approved by the Spanish Competent Authority (AEMPS) as a low intervention clinical trial. Start of recruitment: August, 2020 End of recruitment: May, 2021 TRIAL REGISTRATION: Identifier: EudraCT Number: 2020-002037-15 ; Registration date: 26 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Parvimonas micra: A potential causative pathogen to consider when diagnosing odontogenic brain abscesses.

BACKGROUND: Brain abscess is a life-threatening entity which requires prompt and long-term antibiotic therapy, generally associated with surgical drainage, and eradicating the primary source of infection. Parvimonas micra (Pm) has only been reported once before as the lone infecting organism of an orally originated, solitary brain abscess. Diagnosing brain abscesses caused by this Gram-positive anaerobic coccus, constituent of the oral cavity flora, is challenging, and an optimal treatment regimen has not been well established. We report the diagnosis and successful treatment of a Pm caused odontogenic brain abscess. CASE DESCRIPTION: A 62-year-old immunocompetent male with a right-parietal brain abscess presented with headache and seizures. He was started on empirical antibiotic therapy and subsequently underwent surgical drainage. The only source of infection found was severe periodontitis with infected mandibular cysts. Thus, tooth extraction and cyst curettage were performed 1 week after brain surgery. Cultures of brain abscess fluid were negative, but amplification of bacterial 16S ribosomal RNA (rRNA) with polymerase chain reaction demonstrated Pm. After 3 weeks of intravenous ceftriaxone and metronidazole, the patient was switched to oral metronidazole and moxifloxacin for 6 weeks. CONCLUSIONS: This case highlights the potential risk of untreated dental infections causing brain abscesses. Pm should be considered as a possible pathogen of odontogenic brain abscesses despite its presence usually not being detected by standard bacterial cultures. Therefore, 16S rRNA gene sequencing analysis is strongly recommended for bacterial identification before defining brain abscesses as cryptogenic.

A Retrospective Controlled Cohort Study of the Impact of Glucocorticoid Treatment in SARS-CoV-2 Infection Mortality.

Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range [IQR], 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67]; hazard ratio [HR], 0.51 [95% confidence interval, 0.27 to 0.96]; P = 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 [95% confidence interval, 0.048 to 0.65]). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86]; odds ratio [OR], 0.880 [95% confidence interval, 0.449 to 1.726]; P = 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.

Impacto de la bacteriemia por Pseudomonas aeruginosa en un hospital de tercer nivel: mortalidad y factores pronósticos / Impact of Pseudomonas aeruginosa bacteraemia in a tertiary hospital: Mortality and prognostic factors

Antecedentes y objetivo: La bacteriemia por Pseudomonas aeruginosa se asocia a una mortalidad muy elevada, condicionada por la comorbilidad, el origen y la gravedad del episodio y la ausencia de un tratamiento adecuado. El objetivo del estudio es conocer la mortalidad y los factores pronósticos de la bacteriemia por P.aeruginosa en nuestro hospital. Pacientes y métodos: Se realizó un estudio retrospectivo de las bacteriemias por P.aeruginosa detectadas entre 2009 y 2014. Se calculó la incidencia y se describieron las características epidemiológicas, clínicas y microbiológicas, la mortalidad y sus factores pronósticos. Resultados: Se analizaron 110 episodios de bacteriemia por P.aeruginosa, frecuentemente observadas con antecedentes de hospitalización, comorbilidad e inmunodepresión. La mayoría fue de origen respiratorio o urinario. La presencia de resistencias fue muy elevada. El tratamiento empírico fue adecuado en el 60,0%, y el dirigido, en el 92,3%. La mortalidad global fue del 37,3%, y la atribuible, del 29,1%. Los factores pronósticos más importantes fueron el índice Charlson ≥3, los antecedentes de neoplasia hematológica, neutropenia y uso de corticoides, el origen, el índice de Pitt ≥4, la insuficiencia renal, el tratamiento dirigido adecuado, el tratamiento empírico con piperacilina/tazobactam en pacientes graves y el control del foco. Conclusiones: La bacteriemia por P.aeruginosa se asocia a una mortalidad muy elevada, posiblemente más relacionada con las condiciones previas del paciente y la gravedad del episodio que con el tratamiento elegido. No obstante, el principal objetivo en el manejo sigue siendo optimizar el tratamiento, incluyendo el control del foco

Background and objectives: Pseudomonas aeruginosa bacteraemia is associated with a very high mortality, conditioned by comorbidity, source, severity of the episode and lack of adequate treatment. The aim of the study is to know the mortality and prognostic factors of bacteraemia by P.aeruginosa in our hospital. Patients and methods: We conducted a retrospective study of P.aeruginosa bacteraemia detected between 2009 and 2014. Epidemiological, clinical and microbiological characteristics were described. A risk factor analysis for mortality was performed. Results: We analysed 110 episodes of bacteraemia, which was more frequent in men of advanced age and with a history of hospitalisation, comorbidity and immunosuppression. Most of the bacteraemias were secondary (mainly of respiratory or urinary source) and led to a significant clinical deterioration. The presence of antibiotic resistance was very high, with 27.3% of multiresistant strains. Empirical treatment was adequate in 60.0% and 92.3% for definite treatment. Overall mortality was 37.3% and attributable mortality was 29.1%. The most important prognostic factors were Charlson index ≥3, history of haematologic malignancy, neutropenia and previous use of corticosteroids, source of bacteraemia, Pitt index ≥4, renal insufficiency, adequate definite treatment, empiric treatment with piperacillin/tazobactam in severe episodes and focus control. Conclusion: P.aeruginosa bacteraemia is associated with a very high mortality, possibly more related to previous comorbidity and severity of the episode than to the treatment chosen. However, the main goal in management remains to optimise treatment, including focus control

Impact of Pseudomonas aeruginosa bacteraemia in a tertiary hospital: Mortality and prognostic factors. / Impacto de la bacteriemia por Pseudomonas aeruginosa en un hospital de tercer nivel: mortalidad y factores pronósticos.

BACKGROUND AND OBJECTIVES: Pseudomonas aeruginosa bacteraemia is associated with a very high mortality, conditioned by comorbidity, source, severity of the episode and lack of adequate treatment. The aim of the study is to know the mortality and prognostic factors of bacteraemia by P.aeruginosa in our hospital. PATIENTS AND METHODS: We conducted a retrospective study of P.aeruginosa bacteraemia detected between 2009 and 2014. Epidemiological, clinical and microbiological characteristics were described. A risk factor analysis for mortality was performed. RESULTS: We analysed 110 episodes of bacteraemia, which was more frequent in men of advanced age and with a history of hospitalisation, comorbidity and immunosuppression. Most of the bacteraemias were secondary (mainly of respiratory or urinary source) and led to a significant clinical deterioration. The presence of antibiotic resistance was very high, with 27.3% of multiresistant strains. Empirical treatment was adequate in 60.0% and 92.3% for definite treatment. Overall mortality was 37.3% and attributable mortality was 29.1%. The most important prognostic factors were Charlson index ≥3, history of haematologic malignancy, neutropenia and previous use of corticosteroids, source of bacteraemia, Pitt index ≥4, renal insufficiency, adequate definite treatment, empiric treatment with piperacillin/tazobactam in severe episodes and focus control. CONCLUSION: P.aeruginosa bacteraemia is associated with a very high mortality, possibly more related to previous comorbidity and severity of the episode than to the treatment chosen. However, the main goal in management remains to optimise treatment, including focus control.

Clostridium difficile: deleterious impact on hematopoietic stem cell transplantation.

C. difficile infection (CDI), the most common cause of hospital-acquired diarrhea, is very frequent after hematopoietic stem cell transplantation (HSCT). Recent publications suggest it affects between 6 % and 20 % of HSCT recipients during the first year and is more common following allogeneic transplant (allo-HSCT). The best diagnostic strategy remains to be defined, but molecular testing for the toxin genes by polymerase chain reaction (PCR) seems to be replacing the traditional enzyme immunoassays (EIA). The higher sensitivity of the PCR may result in increased measured incidence of disease. C. difficile infection typically occurs during the first month after HSCT. Although the course of CDI after HSCT does not seem to be different than in other hospitalized patients, it may result in worsening of bowel graft versus host disease (GVHD) after allo-HSCT. Current evidence suggests a reciprocal effect by which GVHD may increase the risk of CDI and C. difficile disease may increase the risk of GVHD. Metronidazole was the treatment most commonly used in all recent series, followed by the combination metronidazole and oral vancomycin. There is minimal information on the use of fidaxomicin in HSCT recipients. Regarding stool transplant, there is one case report of successful use of this modality in an HSCT recipient. These two newer approaches will certainly be investigated in the future.