Mitochondrial dysfunction, lipids metabolism, and amino acid biosynthesis are key pathways for COVID-19 recovery.

The metabolic alterations caused by SARS-CoV-2 infection reflect disease progression. To analyze molecules involved in these metabolic changes, a multiomics study was performed using plasma from 103 patients with different degrees of COVID-19 severity during the evolution of the infection. With the increased severity of COVID-19, changes in circulating proteomic, metabolomic, and lipidomic profiles increased. Notably, the group of severe and critical patients with high HRG and ChoE (20:3) and low alpha-ketoglutaric acid levels had a high chance of unfavorable disease evolution (AUC = 0.925). Consequently, patients with the worst prognosis presented alterations in the TCA cycle (mitochondrial dysfunction), lipid metabolism, amino acid biosynthesis, and coagulation. Our findings increase knowledge regarding how SARS-CoV-2 infection affects different metabolic pathways and help in understanding the future consequences of COVID-19 to identify potential therapeutic targets.

In Vitro Antibacterial Activity of Silver Nanoparticles Conjugated with Amikacin and Combined with Hyperthermia against Drug-Resistant and Biofilm-Producing Strains.

In view of the current increase and spread of antimicrobial resistance (AMR), there is an urgent need to find new strategies to combat it. This study had two aims. First, we synthesized highly monodispersed silver nanoparticles (AgNPs) of approximately 17 nm, and we functionalized them with mercaptopoly(ethylene glycol) carboxylic acid (mPEG-COOH) and amikacin (AK). Second, we evaluated the antibacterial activity of this treatment (AgNPs_mPEG_AK) alone and in combination with hyperthermia against planktonic and biofilm-growing strains. AgNPs, AgNPs_mPEG, and AgNPs_mPEG_AK were characterized using a suite of spectroscopy and microscopy methods. Susceptibility to these treatments and AK was determined after 24 h and over time against 12 clinical multidrug-resistant (MDR)/extensively drug-resistant (XDR) isolates of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The efficacy of the treatments alone and in combination with hyperthermia (1, 2, and 3 pulses at 41°C to 42°C for 15 min) was tested against the same planktonic strains using quantitative culture and against one P. aeruginosa strain growing on silicone disks using confocal laser scanning microscopy. The susceptibility studies showed that AgNPs_mPEG_AK was 10-fold more effective than AK alone, and bactericidal efficacy after 4, 8, 24, or 48 h was observed against 100% of the tested strains. The combination of AgNPs_mPEG_AK and hyperthermia eradicated 75% of the planktonic strains and exhibited significant reductions in biofilm formation by P. aeruginosa in comparison with the other treatments tested, except for AgNPs_mPEG_AK without hyperthermia. In conclusion, the combination of AgNPs_mPEG_AK and hyperthermia may be a promising therapy against MDR/XDR and biofilm-producing strains. IMPORTANCE Antimicrobial resistance (AMR) is one of the greatest public health challenges, accounting for 1.27 million deaths worldwide in 2019. Biofilms, a complex microbial community, directly contribute to increased AMR. Therefore, new strategies are urgently required to combat infections caused by AMR and biofilm-producing strains. Silver nanoparticles (AgNPs) exhibit antimicrobial activity and can be functionalized with antibiotics. Although AgNPs are very promising, their effectiveness in complex biological environments still falls below the concentrations at which AgNPs are stable in terms of aggregation. Thus, improving the antibacterial effectiveness of AgNPs by functionalizing them with antibiotics may be a significant change to consolidate AgNPs as an alternative to antibiotics. It has been reported that hyperthermia has a large effect on the growth of planktonic and biofilm-producing strains. Therefore, we propose a new strategy based on AgNPs functionalized with amikacin and combined with hyperthermia (41°C to 42°C) to treat AMR and biofilm-related infections.

Hyperthermia Prevents In Vitro and In Vivo Biofilm Formation on Endotracheal Tubes.

There is currently an urgent need to find new strategies to tackle antimicrobial resistance and biofilm-related infections. This study has two aims. First, we evaluated the in vitro efficacy of hyperthermia in preventing biofilm formation on the surfaces of polyvinyl chloride discs. Second, we assessed the in vivo efficacy of hyperthermia in preventing biofilm formation in endotracheal tubes (ETTs) of a rabbit model. For the in vitro studies, nine clinical extensively drug-resistant/multidrug-resistant Gram-negative isolates of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa and three clinical methicillin-resistant Staphylococcus aureus strains were studied. For biofilm formation, an adhesion step of 30 or 90 min followed by a growth step of 24 h were performed with application of one, two, and three pulses at 42°C for 15 min each pulse after the adhesion step. For the in vivo studies, New Zealand rabbits were intubated with ETTs previously colonized with K. pneumoniae or P. aeruginosa strains, and three pulses at 42°C for 15 min were applied after the adhesion step. The application of three pulses at 42°C for 15 min each pulse was needed to achieve the prevention of the in vitro biofilm formation of 100% of the tested strains. The application of heat pulses in a rabbit intubation model led to biofilm prevention of 85% against two K. pneumoniae strains and 80% against two P. aeruginosa strains compared to the control group. Hyperthermia application through pulses at 42°C could be a new nonantibiotic strategy to prevent biofilm formation in ETTs. IMPORTANCE Biofilm-producing microorganisms are considered medically crucial since they cause 80% of the infections that occur in the human body. Medical devices such as endotracheal tubes (ETTs) can act as a reservoir for pathogens providing the surface to which microorganisms can adhere and cause biofilm-associated infections in critically ill patients. This biofilm has been related with the development of ventilator-associated pneumonia (VAP), with an incidence of 8 to 28%, a mortality rate up to 17% and its associated high extra costs. Although some VAP-preventive measures have been reported, they have not demonstrated a significant reduction of VAP incidence. Therefore, we present a new nonantibiotic strategy based on hyperthermia application to prevent biofilm formation inside ETTs. This technology could reduce VAP incidence, intubation duration, hospital and intensive care unit (ICU) length stays, and mortality rates. Consequently, this could decrease the antibiotics administered and influence the impact of antibiotic resistance in the ICU.

Impact of 18F-FDG-PET/CT on the management of Staphylococcus aureus bacteraemia: a retrospective observational study.

OBJECTIVES: To assess the impact of 18F-FDG-PET/CT on the diagnosis and management of patients with Staphylococcus aureus bacteraemia (SAB). METHODS: Post hoc analysis of a prospective cohort of consecutive adult patients diagnosed with SAB (January 2013-December 2017). Patients who underwent 18F-FDG-PET/CT at the discretion of the attending physician were included. Endpoints were the identification of previously unknown infectious foci and changes in clinical management, defined as changes in the duration or class of antibiotic therapy, a surgical procedure on the source of infection or a change in the decision to remove or retain an implantable device. RESULTS: We included 39 patients (median age: 69 years, IQR:60-79). Fifteen (39%) patients did not have an infectious focus identified before 18F-FDG-PET/CT). Thirty new infectious foci were detected in 22/39 (56%) patients. In 11/15 (73%) patients without an identified focus at least one infectious focus was detected by 18F-FDG-PET/CT. In 22/26 (85%) patients with implantable devices, 18F-FDG-PET/CT confirmed or ruled out infection or detected local complications. Out of 13 device infections, 10 were detected by 18F-FDG-PET/CT (7/10 for the first time). In 19/39 (49%) patients 18F-FDG-PET/CT results led to changes in clinical management (15 changes in antibiotic therapy, 2 device removals, 2 surgical procedures, 1 avoidance of a surgical procedure). CONCLUSIONS: 18F-FDG-PET/CT may be a useful asset in the management of selected SAB cases, allowing the identification of previously undetected infectious foci and optimization of therapy, particularly in patients with endovascular devices. Indication should be made on a case-by-case basis.

Dalbavancin in clinical practice in Spain: a 2†year retrospective study.

Objectives: Dalbavancin is approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) in adults. Its unique pharmacokinetic properties allow daily dosing to be avoided. The objective was to describe the sociodemographic and clinical characteristics of patients treated with dalbavancin in Spain, and to evaluate its effectiveness and safety in real-world settings. Patients and methods: This non-interventional, retrospective, observational and multicentre study included patients who received at least one dose between 2018 and 2019 in seven Spanish hospitals. Results: In total, 187 patients were included. The most common comorbidities were cardiovascular disease (27.4%) and diabetes mellitus (23.5%). Dalbavancin was used to treat osteoarticular infections (28.3%), ABSSSIs (22.5%), cardiovascular infections (20.9%) and catheter-related infections (18.2%). The most prevalent pathogens were Staphylococcus aureus (34.2%), CoNS (32.6%), and enterococci (12.8%). The main reason for use was early hospital discharge (65.8%). Most patients were treated with 1500 mg in a single dose (35.3%) and the median duration of treatment was 2 weeks. The treatment was clinically successful in 91.4% of cases. Six patients (3.2%) reported adverse events. Physicians agreed on the potential reduction of hospitalization days (85.3%). A subanalysis of patient characteristics and type of pathogen showed similar results in terms of efficacy and safety. Conclusions: Dalbavancin seems to be effective and safe as second-line treatment in severe Gram-positive infections. It improves treatment adherence and allows outpatient management. Furthermore, the effectiveness and safety profile are maintained against diverse microorganisms in Gram-positive infections and regardless of the patients' comorbidities at baseline, or age.

In Vitro and In Vivo Antimicrobial Activity of Hypochlorous Acid against Drug-Resistant and Biofilm-Producing Strains.

The aims of this study were as follows. First, we determined the antimicrobial efficacy of hypochlorous acid (HClO) against bacterial, fungal, and yeast strains growing planktonically and growing in biofilms. Second, we sought to compare the activity of the combination of daptomycin and HClO versus those of the antimicrobial agents alone for the treatment of experimental catheter-related Staphylococcus epidermidis infection (CRI) using the antibiotic lock technique (ALT) in a rabbit model. HClO was generated through direct electric current (DC) shots at determined amperages and times. For planktonic susceptibility studies, 1 to 3 DC shots of 2, 5, and 10 mA from 0 to 300 s were applied. A DC shot of 20 mA from 0 to 20 min was applied to biofilm-producing strains. Central venous catheters were inserted into New Zealand White rabbits, inoculated with an S. epidermidis strain, and treated with saline solution or ALT using daptomycin (50 mg/mL), HClO (20 mA for 45 min), or daptomycin plus HClO. One hundred percent of the planktonic bacterial, fungal, and yeast strains were killed by applying one DC shot of 2, 5, and 10 mA, respectively. One DC shot of 20 mA for 20 min was sufficient to eradicate 100% of the tested biofilm-producing strains. Daptomycin plus HClO lock therapy showed the highest activity for experimental CRI with S. epidermidis. HClO could be an effective strategy for treating infections caused by extensively drug-resistant or multidrug-resistant and biofilm-producing strains in medical devices and chronic wounds. The results of the ALT using daptomycin plus HClO may be promising. IMPORTANCE Currently, drug-resistant infections are increasing and there are fewer antibiotics available to treat them. Therefore, there is an urgent need to find new antibiotics and nonantimicrobial strategies to treat these infections. We present a new nonantibiotic strategy based on hypochlorous acid generation to treat long-term catheter-related and chronic wounds infections.

Ceftazidime-Avibactam plus Aztreonam for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria.

This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were Enterobacterales in 22 patients and Pseudomonas aeruginosa in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24). CZA/ATM could be considered an alternative therapy for VIM-type-producing GNB infections.

Infective endocarditis in pregnant women without intravenous drug use: a multicentre retrospective case series.

OBJECTIVES: To describe the clinical features and outcomes of infective endocarditis (IE) in pregnant women who do not inject drugs. METHODS: A multinational retrospective study was performed at 14 hospitals. All definite IE episodes between January 2000 and April 2021 were included. The main outcomes were maternal mortality and pregnancy-related complications. RESULTS: Twenty-five episodes of IE were included. Median age at IE diagnosis was 33.2 years (IQR 28.3-36.6) and median gestational age was 30 weeks (IQR 16-32). Thirteen (52%) patients had no previously known heart disease. Sixteen (64%) were native IE, 7 (28%) prosthetic and 2 (8%) cardiac implantable electronic device IE. The most common aetiologies were streptococci (n = 10, 40%), staphylococci (n = 5, 20%), HACEK group (n = 3, 12%) and Enterococcus faecalis (n = 3, 12%). Twenty (80%) patients presented at least one IE complication; the most common were heart failure (n = 13, 52%) and symptomatic embolism other than stroke (n = 4, 16%). Twenty-one (84%) patients had surgery indication and surgery was performed when indicated in 19 (90%). There was one maternal death and 16 (64%) patients presented pregnancy-related complications (11 patients ≥1 complication): 3 pregnancy losses, 9 urgent Caesarean sections, 2 emergency Caesarean sections, 1 fetal death, and 11 preterm births. Two patients presented a relapse during a median follow-up of 3.1 years (IQR 0.6-7.4). CONCLUSIONS: Strict medical surveillance of pregnant women with IE is required and must involve a multidisciplinary team including obstetricians and neonatologists. Furthermore, the potential risk of IE during pregnancy should never be underestimated in women with previously known underlying heart disease.

Skin infections in Europe: a retrospective study of incidence, patient characteristics and practice patterns.

OBJECTIVE: Acute bacterial skin and skin structure infections (ABSSSIs) are associated with considerable morbidity and a heavy healthcare burden. The primary objectives of this two-phase study were to determine the incidence of skin infections and ABSSSIs in hospitalized patients (Phase A), and to describe the characteristics and treatment of hospitalized patients with ABSSSIs (Phase B). METHODS: This non-interventional, retrospective study was based on data collected from adult patients hospitalized for skin infections in six European countries (Czech Republic, Greece, Italy, Portugal, Russia and Spain) between January 2014 and June 2016. RESULTS: In Phase A, the total hospital incidence of skin infections and ABSSSIs was 2.4 and 1.8 per 1000 patient-days, respectively. Overall, 73.6% of 50,469 hospitalizations for skin infections were for ABSSSIs. Among the 750 patients with ABSSSIs included in Phase B, Gram-positive bacteria were isolated in 24.9%, most commonly methicillin-susceptible Staphylococcus aureus (11.5%). Empirical therapy was administered to 98.1% of patients, most often with a penicillin, with or without a ß-lactamase inhibitor (42.1%). Complete cure was achieved in 46.5% and 34.5% of patients after initial treatment and treatment modification, respectively. Overall, 22.7% of patients had at least one additional ABSSSI-related hospitalization, 47.1% of patients visited the emergency room, 19.3% of patients visited primary care clinics, and 34.8% of patients visited a specialist. CONCLUSION: Treatment of ABSSSIs in Europe is associated with a heavy healthcare burden, highlighting the need for optimized management strategies that may reduce healthcare utilization.

Early outcomes in adults hospitalized with severe SARS-CoV-2 infection receiving tocilizumab.

Background: Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19). The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others. Methods: We report the preliminary results from the Vall d'Hebron cohort study at Vall d'Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed SARS-CoV-2 infection and who were treated with tocilizumab until March 25th. Results: 82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3-8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8-5.8) if tocilizumab was administered after the onset of ARDS. Conclusion: Early administration of tocilizumab in patients needing oxygen supplementation may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data regarding the precise timing in of initiation of the treatment with tocilizumab.

Antecedentes: Los tratamientos inmunomoduladores para la prevención del daño pulmonar están siendo ampliamente estudiados contra la COVID-19. El objetivo primario es evaluar la mortalidad a los 7 días después de la administración de tocilizumab. El objetivo secundario es el ingreso en UCI, el desarrollo de distrés respiratorio agudo e insuficiencia respiratoria aguda entre otros. Métodos: Informamos sobre los resultados preliminares de la cohorte del Hospital Universitario Vall d'Hebron en Barcelona (España), que incluye todos los pacientes consecutivos con infección confirmada por SARS-CoV-2 y que recibieron tratamiento con tocilizumab hasta el 25 de marzo 2020. Resultados: Ochenta y dos pacientes con COVID-19 recibieron al menos una dosis de tocilizumab. La edad media (±DE) fue de 59,1 (±19,8) años, el 63% eran hombres, 22% correspondía a paciente nacidos fuera de España, y la mediana (RIC) del índice de Charlson ajustado por edad en el momento basal fue de 3 (1-4) puntos. Sesenta y dos pacientes (75,6%) y 45 pacientes (54,9%) desarrollaron insuficiencia respiratoria y distrés respiratorio agudo respectivamente. La mediana de tiempo desde el inicio de los síntomas hasta el desarrollo de ditrés fue de 8 días (5-11). La mortalidad a los 7 días fue del 26,8% La hazard ratio de mortalidad fue del 3,3; IC 95% 1,3-8,5 (la hazard ratio de mortalidad ajustada por edad fue de 2,1; IC 95% 0,8-5,8) si el tocilizumab se administraba después del inicio del distrés respiratorio. Conclusión: La administración precoz de tocilizumab en pacientes con suplementos de oxígeno podría ser crítica para la recuperación de los pacientes. Nuestros datos podrían ayudar a tomar decisiones clínicas hasta que se disponga de más información sobre el momento adecuado para iniciar el tratamiento con tocilizumab.

Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: Prospective, non-randomized trial.

OBJECTIVES: To assess the efficacy and safety of hydroxychloroquine (HCQ) compared with no treatment in healthcare workers with mild SARS-CoV-2 infection. METHODS: Prospective, non-randomized study. All health professionals with confirmed COVID-19 between April 7 and May 6, 2020, non-requiring initial hospitalization were asked to participate. Patients who accepted treatment were given HCQ for five days (loading dose of 400mg q12h the first day followed by200mg q12h). Control group included patients with contraindications for HCQ or who rejected treatment. Study outcomes were negative conversion and viral dynamics of SARS-CoV-2, symptoms duration and disease progression. RESULT: Overall, 142 patients were enrolled: 87 in treatment group and 55 in control group. The median age was 37 years and 75% were female, with few comorbidities. There were no significant differences in time to negative conversion of PCR between both groups. The only significant difference in the probability of negative conversion of PCR was observed at day 21 (18.7%, 95%CI 2.0-35.4). The decrease of SARS-CoV-2 viral load during follow-up was similar in both groups. A non significant reduction in duration of some symptoms in HCQ group was observed. Two patients with HCQ and 4 without treatment developed pneumonia. No patients required admission to the Intensive Care Unit or died. About 50% of patients presented mild side effects of HCQ, mainly diarrhea. CONCLUSIONS: Our study failed to show a substantial benefit of HCQ in viral dynamics and in resolution of clinical symptoms in health care workers with mild COVID-19.

Empirical use of ß-lactam/ß-lactamase inhibitor combinations does not increase mortality compared with cloxacillin and cefazolin in methicillin-susceptible Staphylococcus aureus bacteraemia: a propensity-weighted cohort study.

OBJECTIVES: To evaluate the effectiveness of empirical therapy with ß-lactam/ß-lactamase inhibitor combinations (BL/BLICs) for MSSA bacteraemia. METHODS: We conducted a post hoc analysis of all adult patients with MSSA bacteraemia who were hospitalized at a Spanish university hospital between 2013 and 2018. We compared 30 day mortality among patients receiving initial therapy with BL/BLICs (de-escalated to cloxacillin or cefazolin within 96 h) versus cloxacillin or cefazolin, using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. RESULTS: We evaluated 373 patients with MSSA bacteraemia. Among them, 198 patients met the eligibility criteria, including 127 patients in the BL/BLICs group and 71 patients in the cloxacillin/cefazolin group. Patients in the BL/BLICs group had a higher Charlson comorbidity index (median, 2 [IQR, 1-4.5] versus 2 [IQR, 0-4]); an increased proportion of high-risk sources (i.e. endocarditis, respiratory sources and bacteraemia of unknown origin [34.6% versus 18.3%]); and an earlier start of antibiotic treatment (median, 0 days [IQR, 0-0] versus 1 day [IQR, 1-2]). Thirty day mortality did not significantly differ between the BL/BLICs and the cloxacillin/cefazolin groups (27 patients [21.3%] versus 13 patients [18.3%]; IPTW-adjusted OR = 0.53 [95% CI, 0.18-1.51]). For secondary outcomes, 7 day mortality and 90 day relapse were not statistically different between study groups (8.7% versus 5.6% [P = 0.62] and 6.2% versus 3.8% [P = 0.81], respectively). CONCLUSIONS: BL/BLICs might be an effective empirical treatment for MSSA bacteraemia when de-escalated to cloxacillin or cefazolin within 96 h from the index blood culture.

Pharmacotherapeutic interventions for the treatment of bacterial prostatitis.

INTRODUCTION: Bacterial prostatitis, acute or chronic, is one of the most prevalent urogenital infections in men. Its diagnosis requires the application of a careful methodology. Gram-negative bacilli are the most frequent causative agents, and in recent years, an increase in the frequency of multiresistant bacteria has been detected. The choice of the optimal antimicrobial treatment requires the selection of drugs with proven in vitro activity associated with good penetration into the prostatic tissue, especially in chronic forms of infection. AREAS COVERED: The aim of this article is to summarize the current evidence regarding the pathogenesis, etiology, empirical and definitive antimicrobial therapy, and new pharmacotherapeutic interventions to improve the prognosis of bacterial acute or chronic prostatitis. EXPERT OPINION: Bacterial prostatitis requires the application of an accurate diagnostic protocol to identify the causative agent and establish the optimal antimicrobial treatment. The structural and biochemical characteristics of prostatic tissue result in poor penetration of antimicrobials; therefore, in the choice of treatment, it is essential to select agents with proven antimicrobial activity and pharmacokinetic characteristics that ensure good and sustained concentrations in this area. Patients with chronic forms of infection require prolonged treatment, and relapses of the infectious process are frequent.

Clinical characteristics and outcome of infective endocarditis due to Abiotrophia and Granulicatella compared to Viridans group streptococci.

OBJECTIVE: To describe the clinical characteristics and outcome of Abiotrophia and Granulicatella infective endocarditis and compare them with Viridans group streptococci infective endocarditis. METHODS: All patients in the International Collaboration on Endocarditis (ICE) - prospective cohort study (PCS) and the ICE-PLUS cohort were included (n = 8112). Data from patients with definitive or possible IE due to Abiotrophia species, Granulicatella species and Viridans group streptococci was analyzed. A propensity score (PS) analysis comparing the ABI/GRA-IE and VGS-IE groups according to a 1:2 ratio was performed. RESULTS: Forty-eight (0.64%) cases of ABI/GRA-IE and 1,292 (17.2%) VGS-IE were included in the analysis. The median age of patients with ABI/GRA-IE was lower than VGS-IE (48.1 years vs. 57.9 years; p = 0.001). Clinical features and the rate of in-hospital surgery was similar between ABI/GRA-IE and VGS-IE (52.1% vs. 45.4%; p = 0.366). Unadjusted in-hospital death was lower in ABI/GRA-IE than VGS-IE (2.1% vs. 8.8%; p = 0.003), and cumulative six-month mortality was lower in ABI/GRA-IE than VGS-IE (2.1% vs. 11.9%; p<0.001). After PS analysis, in-hospital mortality was similar in both groups, but six-month mortality was lower in the ABI/GRA IE group (2.1% vs. 10.4%; p = 0.029). CONCLUSIONS: Patients with ABI/GRA-IE were younger, had similar clinical features and rates of surgery and better prognosis than VGS-IE.

Evolving mortality and clinical outcomes of hospitalized subjects during successive COVID-19 waves in Catalonia, Spain.

BACKGROUND: The changes in shield strategies, treatments, emergence variants, and healthcare pathways might shift the profile and outcome of patients hospitalized with COVID-19 in successive waves of the outbreak. METHODS: We retrospectively analysed the characteristics and in-hospital outcomes of all patients admitted with COVID-19 in eight university hospitals of Catalonia (North-East Spain) between Feb 28, 2020 and Feb 28, 2021. Using a 7-joinpoint regression analysis, we split admissions into four waves. The main hospital outcomes included 30-day mortality and admission to intensive care unit (ICU). FINDINGS: The analysis included 17,027 subjects admitted during the first wave (6800; 39.9%), summer wave (1807; 10.6%), second wave (3804; 22.3%), and third wave (4616; 27.1%). The highest 30-day mortality rate was reported during the first wave (17%) and decreased afterwards, remaining stable at 13% in the second and third waves (overall 30% reduction); the lowest mortality was reported during the summer wave (8%, 50% reduction). ICU admission became progressively more frequent during successive waves. In Cox regression analysis, the main factors contributing to differences in 30-day mortality were the epidemic wave, followed by gender, age, diabetes, chronic kidney disease, and neoplasms. INTERPRETATION: Although in-hospital COVID-19 mortality remains high, it decreased substantially after the first wave and is highly dependent of patient's characteristics and ICU availability. Highest mortality reductions occurred during a wave characterized by younger individuals, an increasingly frequent scenario as vaccination campaigns progress. FUNDING: This work did not receive specific funding.

COVID-19 Follow-App. Mobile App-Based Monitoring of COVID-19 Patients after Hospital Discharge: A Single-Center, Open-Label, Randomized Clinical Trial.

INTRODUCTION: In the midst of a pandemic, apps can be used to provide close follow-up, ensure that patients are monitored at home, avoid excessive pressure on medical facilities, prevent the movement of people (both patients and health professionals), and reduce the risk of infection. OBJECTIVE: To adapt and validate the use of a smartphone application for outpatient follow-up of COVID-19 patients after hospital discharge. METHODS: We conducted an open-label clinical trial at Hospital Universitari Vall d'Hebron in Barcelona, Spain. Patients were randomly assigned in a 1:1 ratio to be followed by the Farmalarm app or by their primary care center. The primary endpoint was the reduction in the need for in-person return visits. RESULTS: From 31 March to 4 May 2020, 150 patients were enrolled in the study at hospital discharge: 74 patients were randomized to the experimental group, and 76 to the control group. All patients in the control group and all except for six in the experimental group completed the study. During hospitalization, before study inclusion, all but 4 (97.3%) had viral pneumonia, 91 (60.7%) required supplemental oxygen, and 16 (10.7%) required intensive care unit (ICU) admission. COVID-19-related return visits to the emergency department were significantly higher in the control group (7.9% vs. 0%; p = 0.028) in the per-protocol analysis. Telephone consultations with the emergency department were performed by 12 (15.8%) patients in the control group and 0 (0%) in the experimental group (p < 0.001). Satisfaction with outpatient monitoring was rated higher by the experimental group (5 vs. 4 points; p < 0.001). CONCLUSIONS: Following COVID-19 hospital discharge, home follow-up via a mobile app was effective in reducing in-person return visits without undermining patient satisfaction or perception of health, compared with standard follow-up.

Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification.

BACKGROUND: STIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed 'Drassanes Exprés', a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention. METHODS: The Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients' sample collection to notification and treatment are analysed. RESULTS: Between 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26-39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2-3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days. CONCLUSIONS: Drassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.

Incidence and risk factors for early readmission after hospitalization for SARS-CoV-2 infection: results from a retrospective cohort study.

PURPOSE: We aim to assess risk factors related to early readmission in previous hospitalized patients with COVID-19. METHODS: We analyzed a retrospective cohort of patients with laboratory-confirmed COVID-19 admitted to Vall d'Hebron University Hospital, Barcelona, Spain. Early readmission was defined as the need for hospitalization within a period of 60 days after discharge. A descriptive analysis of the readmission was performed, including hospitalization outcome. We also performed a multivariate logistic regression to define risk factors for readmission RESULTS: A total of 629 patients were followed up during 60 days with a readmission cumulative incidence of 5.4% (34 out of 629) and an incidence rate of 0.034 person-years. Main reasons for readmission were respiratory worsening (13, 38.2%), decompensation of previous disease (12, 35.3%) or infectious complications (6, 17.6%). Median time to readmission was 12 days (interquartile range 7-33 days). Prior diagnosis of heart failure (OR 4.09; 95% CI 1.35-12.46; p = 0.013), length of stay during index admission greater than 13 days (OR 2.72; 95% CI 1.21-6.12; p = 0.015), treatment with corticosteroids (OR 2.39; 95% CI 1.01-5.70; p = 0.049) and developing pulmonary thromboembolism (OR 11.59; 95% CI 2.89-46.48; p = 0.001) were the risk factors statistically associated with early readmission. CONCLUSION: Readmission cumulative incidence was 5.4%. Those patients with prior diagnosis of heart failure, length of stay greater than 13 days, treated with corticosteroids or who developed pulmonary thromboembolism might benefit from close monitoring after being discharged.

Early outcomes in adults hospitalized with severe SARS-CoV-2 infection receiving tocilizumab.

BACKGROUND: Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19). The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others. METHODS: We report the preliminary results from the Vall d'Hebron cohort study at Vall d'Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed SARS-CoV-2 infection and who were treated with tocilizumab until March 25th. RESULTS: 82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3-8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8-5.8) if tocilizumab was administered after the onset of ARDS. CONCLUSION: Early administration of tocilizumab in patients needing oxygen supplementation may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data regarding the precise timing in of initiation of the treatment with tocilizumab.