Treatment with Rasburicase in Hospitalized Patients with Cardiorenal Syndrome: Old Treatment, New Scenario.

Cardiorenal syndrome (CRS) involves joint dysfunction of the heart and kidney. Acute forms share biochemical alterations like hyperuricaemia (HU) with tumour lysis syndrome (TLS). The mainstay treatment of acute CRS with systemic overload is diuretics, but rasburicase is used in TLS to prevent and treat hyperuricaemia. An observational, retrospective study was performed to assess the effectiveness and safety of a single dose of rasburicase in hospitalized patients with cardiorenal syndrome, worsening renal function and uric acid levels above 9 mg/dL. Rasburicase improved diuresis and systemic congestion in the 35 patients included. A total of 86% of patients did not need to undergo RRT, and early withdrawal was possible in the remaining five. Creatinine (Cr) decreased after treatment with rasburicase from a peak of 3.6 ± 1.27 to 1.79 ± 0.83 mg/dL, and the estimated glomerular filtration rate (eGFR) improved from 17 ± 8 to 41 ± 20 mL/min/1.73 m2 (p = 0.0001). The levels of N-terminal type B Brain Natriuretic Peptide (Nt-ProBNP) and C-reactive protein (CRP) were also significantly reduced. No relevant adverse events were detected. Our results show that early treatment with a dose of rasburicase in patients with CRS and severe HU is effective to improve renal function and systemic congestion, avoiding the need for sustained extrarenal clearance, regardless of comorbidities and ventricular function.

Impact of preoperative pharmaceutical care consultation on medication errors in surgical patients: a comprehensive analysis.

OBJECTIVE: Assessing the impact of introducing preoperative pharmaceutical care consultations by analyzing the severity of prevented medication errors (MEs) and their potential effects on the surgical process. METHODS: Preoperative pharmaceutical care consultation was implemented in our hospital to assess the preoperative medication management of surgical patients between the pre-anesthesia consultation and the day of surgery. Pharmacists evaluated the appropriateness of medication management based on a consensus multidisciplinary institutional protocol. All errors identified between 2016 and 2020 were analyzed, and their severity and potential impact on surgery were standardized. A list of therapeutic groups was created to prioritize patients for consultations. RESULTS: During the study period, 3,105 patients attended the consultations and 1,179 MEs were prevented. According to severity, 30.6% of MEs were classified as category E and 26.2% as D. The Number Needed to Treat to prevent a category E or higher ME (indicating potential harm to patients) was 5 patients. About 14.84% of MEs belonged to the prioritized drug groups. One hundred and thirteen errors would have resulted in a surgery delay of more than 24 h, and 175 errors were classified as G-H (irreversible damage). CONCLUSIONS: This study highlights the effectiveness of pharmaceutical care consultations in preventing MEs and improving surgical outcomes.

[Translated article] Influence of augmented renal clearance in the lower incidence of linezolid-related haematological toxicity.

OBJECTIVES: Linezolid is an oxazolidin commonly related to the development of haematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced haematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. MATERIAL AND METHODS: A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014-2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60-90 mL/min) were compared. Haematological toxicity was defined as a decrease of 25% in platelets, of 25% in haemoglobin, and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of haematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentage diminution of all 3 parameters was calculated and compared by Mann-Whitney test and treatment interruption and transfusion requirements were registered. RESULTS: 30 ARC patients and 38 reference patients were included. Haematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (P=.014); thrombocytopenia in 13.33% vs 36.84% (P=.051), anaemia in 3.3% vs 10.52% (P=.374) and neutropenia in 10% vs 23.68% (P=.204). Median percentage of platelets decrease in ARC patients was -10.36 (-193.33-62.03) vs 2.68 (-163.16-82.71) in reference patients (P=.333), while haemoglobin decrease was 2.50 (-12.12-25.93) vs 9.09 (-17.72-30.63) (P=.047) and neutrophils decrease was 9.14 (-73.91-76.47) vs 27.33 (-86.66-90.90) (P=.093). 10.5% of normal renal function patients reported at least 1 adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had transfusion requirements. No major events or interruptions were reported in ARC patients. CONCLUSION: Our findings suggest a lower incidence and clinical relevance of haematological toxicity in augmented renal clearance patients. Thrombocytopenia was the major event in both populations. This might be related to a lower exposure to the drug due to the higher clearance and likely lower therapeutic efficiency. These results suggest a potential benefit of therapeutic drug monitoring on high risk patients.

Influencia de la hiperfiltración glomerular en la menor toxicidad hematológica inducida por linezolid / Influence of augmented renal clearance on the lower incidence of linezolid-related hematological toxicity

Objetivos linezolid es una oxazolidina frecuentemente implicada en el desarrollo de toxicidad hematológica, siendo el aclaramiento renal el mecanismo mayoritario en su eliminación. Se evaluó la influencia de la hiperfiltración glomerular en la toxicidad hematológica inducida por linezolid en pacientes con aclaramiento incrementado frente a pacientes con función renal normal. Material y métodos se diseñó un estudio observacional y retrospectivo en pacientes hospitalizados, tratados al menos 5 días con linezolid entre 2014 y 2019. Se compararon pacientes con aclaramiento de creatinina incrementado (≥130 mL/min) y normal (60–90 mL/min). Se definió la toxicidad hematológica como el descenso en plaquetas y hemoglobina del 25% y en neutrófilos del 50% frente a los valores basales. Se clasificó el grado de toxicidad según Common Terminology Criteria for Adverse Events v5 y se comparó la incidencia entre ambos grupos mediante Chi-cuadrado y Fisher. Así mismo, se calculó el porcentaje de disminución de los 3 parámetros y su asociación mediante el test de Mann–Whitney y se registraron las interrupciones y transfusiones asociadas.Resultados se evaluaron 30 pacientes hiperfiltradores y 38 normofiltradores. El 16,66% de hiperfiltradores presentó toxicidad hematológica frente al 44,74% (p = 0,014). La trombocitopenia fue del 13,33 vs. 36,84% (p = 0,051), la anemia del 3,3 vs. 10,52% (p = 0,374) y la neutropenia del 10 vs. 23,68% (p = 0,204). La mediana del porcentaje de descenso plaquetario en hiperfiltradores frente a normofiltradores fue del −10,36 (−193,33–62,03) vs. 2,68 (−163,16–82,71) (p = 0,333), de hemoglobina 2,50 (−12,12–25,93) vs. 9,09 (−17,72–30,63) (p = 0,047) y de neutrófilos 9,14 (−73,91–76,47) vs. 27,33 (−86,66–90,90) (p = 0,093). El 10,5% con filtrado normal presentó toxicidad grado 3 o superior, el 2,6% interrumpió el tratamiento y el 5,2% requirieron transfusiones... (AU)

Objectives Linezolid is an oxazolidin commonly related to the development of hematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced hematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. Material and methods A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014–2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60–90 mL/min) were compared. Hematological toxicity was defined as a decrease of 25% in platelets, of 25% in hemoglobin and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of hematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentaje disminution of all three parameters was calculated and compared by Mann–Whitney test and treatment interruption and tranfusion requirements were registered. Results 30 ARC patients and 38 reference patients were included. Hematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (p = 0.014); thrombocytopenia in 13.33% vs 36.84% (p = 0.051), anemia in 3.3% vs 10.52% (p = 0.374) and neutropenia in 10% vs 23.68% (p = 0.204). Median percentaje of platelets decrease in ARC patients was −10.36 (−193.33–62.03) vs 2.68 (−163.16–82.71) in reference patients (p = 0.333), while hemoglobin decrease was 2.50 (−12.12–25.93) vs 9.09 (−17.72–30.63) (p = 0.047) and neutrophils decrease was 9.14 (−73.91–76.47) vs 27.33 (−86.66–90.90) (p = 0.093). 10.5% of normal renal function patients reported at least one adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had tranfusion requirements... (AU)

Influence of augmented renal clearance on the lower incidence of linezolid-related hematological toxicity. / Influencia de la hiperfiltración glomerular en la menor toxicidad hematológica inducida por linezolid.

OBJECTIVES: Linezolid is an oxazolidin commonly related to the development of hematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced hematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. MATERIAL AND METHODS: A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014-2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60-90 mL/min) were compared. Hematological toxicity was defined as a decrease of 25% in platelets, of 25% in hemoglobin and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of hematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentaje disminution of all three parameters was calculated and compared by Mann-Whitney test and treatment interruption and tranfusion requirements were registered. RESULTS: 30 ARC patients and 38 reference patients were included. Hematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (p = 0.014); thrombocytopenia in 13.33% vs 36.84% (p = 0.051), anemia in 3.3% vs 10.52% (p = 0.374) and neutropenia in 10% vs 23.68% (p = 0.204). Median percentaje of platelets decrease in ARC patients was -10.36 (-193.33-62.03) vs 2.68 (-163.16-82.71) in reference patients (p = 0.333), while hemoglobin decrease was 2.50 (-12.12-25.93) vs 9.09 (-17.72-30.63) (p = 0.047) and neutrophils decrease was 9.14 (-73.91-76.47) vs 27.33 (-86.66-90.90) (p = 0.093). 10.5% of normal renal function patients reported at least one adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had tranfusion requirements. No major events or interruptions were reported in ARC patients. CONCLUSION: Our findings suggest a lower incidence and clinical relevance of hematological toxicity in augmented renal clearance patients. Thrombocytopenia was the major event in both populations. This might be related to a lower exposure to the drug due to the higher clearance and likely lower therapeutic efficiency. These results suggest a potential benefit of therapeutic drug monitoring on high risk patients.

Rheumatoid meningitis in a patient with overlap syndrome: The usefulness of anti-citrullinated peptide antibodies determination in CSF.

Rheumatoid meningitis (RM) is a rare complication of rheumatoid arthritis that can manifest as stroke-like episodes. We present the case of a 63-year-old woman with a past history of overlap syndrome and clinical manifestations suggestive of amyopathic dermatomyositis, rheumatoid arthritis, and systemic lupus erythematosus. She presented to the emergency department with sudden onset right-sided clumsiness and numbness, as well as a 2-week history of left hemicranial headache. Laboratory workup revealed positive serum antinuclear antibodies, anti-Ro antibodies, anti-citrullinated peptide antibodies (ACPA), and elevated rheumatoid factor. Lymphocytic pleocytosis, positive ACPA and anti-Ro antibodies with passive diffusion pattern, and negative microbiological studies were demonstrated in the CSF. Brain magnetic resonance imaging showed predominant left fronto-parieto-occipital leptomeningeal and pachimeningeal enhancement. She was diagnosed with RM and received methylprednisolone IV mg/kg once daily. Stroke-like episodes in the setting of a patient with lymphocytic pleocytosis in the cerebrospinal fluid (CSF) and meningeal enhancement should raise suspicion of RM. In this context, serum rheumatoid factor and ACPA levels should always be measured and ACPA should also be measured in CSF. To our knowledge, this is the first reported case of RM in the context of an overlap syndrome. ACPA levels in CSF could be a relevant diagnostic clue in the setting of central nervous system disturbance and overlapping autoimmune conditions that include rheumatoid arthritis. In our case, the presence of a suggestive clinical scenario of RM reinforces the probable pathogenic role of ACPA when it is present in the central nervous system, even without intrathecal synthesis evidence.

[Translated article] Achieving excellence in the pharmaceutical care of the surgical patient.

The perioperative setting is one of the hospital areas with the highest prevalence of medication errors. Despite the wide experience of hospital pharmacists in developing medication safety programs and improvement initiatives, the perioperative setting has remained one of the areas in which there is less experience. Clinical pharmacist should be integrated into the multidisciplinary care team so that they can be involved in the different surgical phases of care, which include from the preoperative assessment to inpatient stay, and finally discharge from hospital. Their work will consist of coordinating and implementing strategies that have been demonstrated to reduce medication errors during the perioperative process. The aim of this paper is to introduce a specialized pharmaceutical care program to achieve excellence in the pharmaceutical care of surgical patients. This program is especially aimed at promoting the figure of the clinical pharmacist in the perioperative setting to guarantee the highest quality and safety in pharmacotherapeutic care throughout all the surgical phases of care.

Appropriateness of Empirical Antibiotic Therapy for Cervicitis and Urethritis Prescribed in the Emergency Department.

Objectives: Sexually transmitted infections are a prevalent global health care problem. Treatment guidelines have recently been updated as a result of antimicrobial resistance and public health trends. The aim of the study was to assess the appropriateness of empirical antibiotic therapy prescribed for cervicitis and urethritis in the emergency department. Methods: We designed a retrospective observational cohort study. We included adult patients with suspected cervicitis or urethritis who attended the emergency department of a tertiary hospital in 2020. We excluded patients with suspected pelvic inflammatory disease, pregnancy or prostatitis and those requiring admission to hospital. Appropriateness of empirical antibiotic therapy was evaluated taking into account 4 aspects: indication, dosing, duration of therapy, and route of administration. Data were obtained from the electronic medical record, the electronic prescription program, and the discharge summary. Results: The study population comprised 176 patients; mean age was 28.9 years (SD = 7.7), and 90.9% were men. The most prescribed treatment was the combination of ceftriaxone and azithromycin (83.0%). Treatment was inappropriate in 71.6% of patients. A total of 159 drug errors were recorded. The most frequent cause was undertreatment (36.4%) related to underdosing (46.5%), particularly with regard to ceftriaxone. The percentage of errors was 11.9% for indication, 84.9% for dosing, 3.1% for duration, and 0% for route of administration. Conclusions: A high percentage of patients who attended the emergency department for suspected cervicitis or urethritis received an inappropriate empirical antibiotic regimen. The main reason was undertreatment due to underdosing.

Achieving excellence in the pharmaceutical care of the surgical patient. / Hacia la excelencia en la atención farmacéutica al paciente quirúrgico.

The perioperative setting is one of the hospital areas with the highest prevalence of medication errors. Despite the wide experience of hospital pharmacists in developing medication safety programs and improvement initiatives, the surgical environment has remained one of the areas in which there is less experience. Clinical pharmacist should be integrated into the multidisciplinary care teams so that they can be involved in the different surgical phases of care, which include from the preoperative assessment to inpatient stay, and finally discharge from hospital. Their work will consist of coordinating and implementing strategies that have been demonstrated to reduce medication errors throughout the perioperative process. The aim of this paper is to introduce a specialized pharmaceutical care program to achieve excellence in the pharmaceutical care of surgical patients. This program is especially aimed at promoting the figure of the clinical pharmacist in the perioperative setting to guarantee the highest quality and safety in pharmacotherapeutic care throughout all the surgical phases of care.

Hacia la excelencia en la atención farmacéutica al paciente quirúrgico / Achieving excellence in the pharmaceutical care of the surgical patient

El proceso quirúrgico es una de las áreas del hospital con más prevalencia de errores de medicación. A pesar de la amplia experiencia del farmacéutico en el desarrollo de prácticas seguras de utilización de los medicamentos, el bloque quirúrgico ha sido una de las áreas en las que menos experiencia existe.El farmacéutico especialista debe integrarse en el equipo multidisciplinar, de tal forma que pueda estar presente en todas las etapas de atención al enfermo (prehospitalización, precirugía, intracirugía, postcirugía y alta). Su función será coordinar y diseñar la puesta en marcha de diferentes estrategias que han demostrado reducir el riesgo de errores de medicación durante todo el proceso perioperatorio.El objetivo del presente trabajo es presentar un programa de atención farmacéutica especializada para alcanzar la excelencia en la atención farmacéutica del paciente quirúrgico. Este programa está dirigido especialmente a visibilizar la figura del farmacéutico en el entorno perioperatorio, para que pueda colaborar en garantizar una atención farmacoterapéutica de máxima calidad y seguridad en todas las etapas. (AU)

The perioperative setting is one of the hospital areas with the highest prevalence of medication errors. Despite the wide experience of hospital pharmacists in developing medication safety programs and improvement initiatives, the surgical environment has remained one of the areas in which there is less experience.Clinical pharmacist should be integrated into the multidisciplinary care teams so that they can be involved in the different surgical phases of care, which include from the preoperative assessment to inpatient stay, and finally discharge from hospital. Their work will consist of coordinating and implementing strategies that have been demonstrated to reduce medication errors throughout the perioperative process.The aim of this paper is to introduce a specialized pharmaceutical care program to achieve excellence in the pharmaceutical care of surgical patients. This program is especially aimed at promoting the figure of the clinical pharmacist in the perioperative setting to guarantee the highest quality and safety in pharmacotherapeutic care throughout all the surgical phases of care. (AU)

Adaptation and validation of the Interprofessional Socialization and Valuing Scale (ISVS) in Spanish university health sciences students.

Many interprofessional education programs are being designed to help students improve their collaborative practice. Traditionally, the evaluation of these programs is focused on attitudes, knowledge and skills, but according to some authors, the evaluation of these activities should be expanded to include the evaluation of the development of an interprofessional identity. The Interprofessional Socialization and Valuing Scale (ISVS) is a self-report tool used to measure interprofessional socialization, but it has not been validated with Spanish students. In this study, the tool was translated into Spanish and administered to a sample of 645 undergraduate students. The data were analyzed to estimate structural validity, internal consistency and convergent validity. Regarding the structural validity, our data supported the unidimensional model found in the English version of the ISVS-21 (normed chi-square = 2.3, RMSEA = 0.045, SRMR = 0.087, CFI = 0.963 and TLI = 0.969). The internal consistency reliability of the scale was adequate, Cronbach α = 0.913 [95% CI 0.903, 0.923]. The Spanish version of the ISVS-21 shows adequate psychometric properties in terms of the construct validity (structural validity and convergent validity) and internal consistency of its scores. This study provides the Spanish-speaking population with an adaptation of the only instrument that has been specifically developed to assess interprofessional socialization.

Permanent renal sequelae secondary to drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome induced by quetiapine.

We describe a Caucasian man in his late 60s who was admitted to the intensive care unit (ICU) with a history of cardiogenic shock secondary to an acute myocardial infarction. The patient's baseline serum creatinine levels were 0.9-1 mg/dL. On day 7 of the admission treatment with quetiapine was initiated due to a delirium episode. The next day the patient developed an erythematous-maculopapular rash and fever, with eosinophilia in the blood count. Over the following days the patient experienced an acute deterioration of kidney function requiring continuous renal replacement therapy. The skin lesions and eosinophilia resolved after withdrawal of quetiapine and systemic steroid therapy was administered. The patient was discharged from the ICU with a serum creatinine level of 2.6 mg/dL. Three months later, blood tests showed no recovery of the kidney function. According to the Naranjo adverse drug reaction probability scale, this event would be classified as 'probable' DRESS syndrome and, based on the RegiSCAR scoring system, was classified as 'definite' DRESS syndrome.

Use of Different Food Classification Systems to Assess the Association between Ultra-Processed Food Consumption and Cardiometabolic Health in an Elderly Population with Metabolic Syndrome (PREDIMED-Plus Cohort).

The association between ultra-processed food (UPF) and risk of cardiometabolic disorders is an ongoing concern. Different food processing-based classification systems have originated discrepancies in the conclusions among studies. To test whether the association between UPF consumption and cardiometabolic markers changes with the classification system, we used baseline data from 5636 participants (48.5% female and 51.5% male, mean age 65.1 ± 4.9) of the PREDIMED-Plus ("PREvention with MEDiterranean DIet") trial. Subjects presented with overweight or obesity and met at least three metabolic syndrome (MetS) criteria. Food consumption was classified using a 143-item food frequency questionnaire according to four food processing-based classifications: NOVA, International Agency for Research on Cancer (IARC), International Food Information Council (IFIC) and University of North Carolina (UNC). Mean changes in nutritional and cardiometabolic markers were assessed according to quintiles of UPF consumption for each system. The association between UPF consumption and cardiometabolic markers was assessed using linear regression analysis. The concordance of the different classifications was assessed with intra-class correlation coefficients (ICC3, overall = 0.51). The highest UPF consumption was obtained with the IARC classification (45.9%) and the lowest with NOVA (7.9%). Subjects with high UPF consumption showed a poor dietary profile. We detected a direct association between UPF consumption and BMI (p = 0.001) when using the NOVA system, and with systolic (p = 0.018) and diastolic (p = 0.042) blood pressure when using the UNC system. Food classification methodologies markedly influenced the association between UPF consumption and cardiometabolic risk markers.

Creation of Tissue-Engineered Urethras for Large Urethral Defect Repair in a Rabbit Experimental Model.

Introduction: Tissue engineering is a potential source of urethral substitutes to treat severe urethral defects. Our aim was to create tissue-engineered urethras by harvesting autologous cells obtained by bladder washes and then using these cells to create a neourethra in a chronic large urethral defect in a rabbit model. Methods: A large urethral defect was first created in male New Zealand rabbits by resecting an elliptic defect (70 mm2) in the ventral penile urethra and then letting it settle down as a chronic defect for 5-6 weeks. Urothelial cells were harvested noninvasively by washing the bladder with saline and isolating urothelial cells. Neourethras were created by seeding urothelial cells on a commercially available decellularized intestinal submucosa matrix (Biodesign® Cook-Biotech®). Twenty-two rabbits were divided into three groups. Group-A (n = 2) is a control group (urethral defect unrepaired). Group-B (n = 10) and group-C (n = 10) underwent on-lay urethroplasty, with unseeded matrix (group-B) and urothelial cell-seeded matrix (group-C). Macroscopic appearance, radiology, and histology were assessed. Results: The chronic large urethral defect model was successfully created. Stratified urothelial cultures attached to the matrix were obtained. All group-A rabbits kept the urethral defect size unchanged (70 ± 2.5 mm2). All group-B rabbits presented urethroplasty dehiscence, with a median defect of 61 mm2 (range 34-70). In group-C, five presented complete correction and five almost total correction with fistula, with a median defect of 0.3 mm2 (range 0-12.5), demonstrating a significant better result (p = 7.85 × 10-5). Urethrography showed more fistulas in group-B (10/10, versus 5/10 in group-C) (p = 0.04). No strictures were found in any of the groups. Group-B histology identified the absence of ventral urethra in unrepaired areas, with squamous cell metaplasia in the edges toward the defect. In group-C repaired areas, ventral multilayer urothelium was identified with cells staining for urothelial cell marker cytokeratin-7. Conclusions: The importance of this study is that we used a chronic large urethral defect animal model and clearly found that cell-seeded transplants were superior to nonseeded. In addition, bladder washing was a feasible method for harvesting viable autologous cells in a noninvasive way. There is a place for considering tissue-engineered transplants in the surgical armamentarium for treating complex urethral defects and hypospadias cases.

COVID-19 in hospitalised patients in Spain: a cohort study in Madrid.

Few large series describe the clinical characteristics, outcomes and costs of COVID-19 in Western countries. This cohort reports the first 1255 adult cases receiving anti-COVID-19 treatment at a Spanish hospital (1-24 March 2020). Treatment costs were calculated. A logistic regression model was used to explore risk factors on admission associated with ARDS. A bivariate Cox proportional hazard ratio (HR) model was employed to determine the HR between individual factors and death. We included 1255 patients (median age 65 years; 57.8% male), of which 92.3% required hospitalisation. The prevalence of hypertension, cardiovascular disease and diabetes mellitus (DM) was 45.1%, 31.4% and 19.9%, respectively. Lymphocytopenia (54.8%), elevated alanine aminotransferase (33.0%) and elevated lactate dehydrogenase (58.5%) were frequent. Overall, 36.7% of patients developed ARDS, 10.0% were admitted to an ICU and 21.3% died. The most frequent antiviral combinations were lopinavir/ritonavir plus hydroxychloroquine (44.2%), followed by triple therapy with interferon beta-1b (32.7%). Corticosteroids and tocilizumab were used in 25.3% and 12.9% of patients, respectively. Total cost of anti-COVID-19 agents was €511 825 (€408/patient). By multivariate analysis, risk factors associated with ARDS included older age, obesity, DM, severe hypoxaemia, lymphocytopenia, increased creatine kinase and increased C-reactive protein. In multivariate Cox model, older age (HR 1.07, 95% CI 1.06-1.09), cardiovascular disease (HR 1.34, 95% CI 1.01-1.79), DM (HR 1.45, 95% CI 1.09-1.92), severe hypoxaemia (HR 2.01, 95% CI 1.49-2.72), lymphocytopenia (HR 1.62, 95% CI 1.20-2.20) and increased C-reactive protein (HR 1.04, 95% CI 1.02-1.06) were risk factors for mortality.

Bilateral fungal infection inducing a serpiginous-like picture.

PURPOSE: To report the clinical findings of a patient who presented with an atypical bilateral fungal retinitis that was established by retinochoroidal biopsy. METHODS: Case report. RESULTS: A 56-year-old systemically healthy man presented with progressive visual loss in his left eye for 3 weeks. Visual acuity was 20/40 in the left eye, and 20/20 in the right eye and fundus examination showed macular retinal pigmented epithelium changes in his left eye. Over the following four months, his lesions progressed to serpiginous-like widespread retinal pigmented epithelium atrophy and his visual acuity decreased to 20/100, but no signs of ocular inflammation were found. Treatment with oral corticoids, valganciclovir and trimethoprim/sulfamethoxazole showed no efficacy. Blood analysis and cultures, laboratory investigations, and imaging tests were carried out looking for infectious and inflammatory diseases, but all tests were negative. Two months later, the patient presented with the same kind of lesions in the other eye (right eye), so he was subjected to retinochoroidal biopsy. Histopathological examination of specimen revealed the presence of intraretinal and choroidal fungal hyphae. Oral voriconazole was initiated achieving clinical remission, but no visual improvement was obtained. The source of the infection remains unknown since all tests results were negative. However, his profession as brewmaster might be related to the origin of the infection. CONCLUSION: Diagnosis of intraocular fungal infection can be challenging. Retinochoroidal biopsy may be useful to establish the diagnosis in those atypical cases with nonrevealing workup and inflammation localized to the retina.

Lipid-Iron Nanoparticle with a Cell Stress Release Mechanism Combined with a Local Alternating Magnetic Field Enables Site-Activated Drug Release.

Most available cancer chemotherapies are based on systemically administered small organic molecules, and only a tiny fraction of the drug reaches the disease site. The approach causes significant side effects and limits the outcome of the therapy. Targeted drug delivery provides an alternative to improve the situation. However, due to the poor release characteristics of the delivery systems, limitations remain. This report presents a new approach to address the challenges using two fundamentally different mechanisms to trigger the release from the liposomal carrier. We use an endogenous disease marker, an enzyme, combined with an externally applied magnetic field, to open the delivery system at the correct time only in the disease site. This site-activated release system is a novel two-switch nanomachine that can be regulated by a cell stress-induced enzyme at the cellular level and be remotely controlled using an applied magnetic field. We tested the concept using sphingomyelin-containing liposomes encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin. We engineered the liposomes by adding paramagnetic beads to act as a receiver of outside magnetic energy. The developed multifunctional liposomes were characterized in vitro in leakage studies and cell internalization studies. The release system was further studied in vivo in imaging and therapy trials using a squamous cell carcinoma tumor in the mouse as a disease model. In vitro studies showed an increased release of loaded material when stress-related enzyme and magnetic field was applied to the carrier liposomes. The theranostic liposomes were found in tumors, and the improved therapeutic effect was shown in the survival studies.