Invasive aspergillosis in liver transplant recipients in the current era.

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted antimold prophylactic and appropriate treatment strategies against IA.

Epilepsy Care in Latin America and the Caribbean: Overcoming Challenges and Embracing Opportunities.

The burden of epilepsy in the Latin America and the Caribbean (LAC) region causes a profound regional impact on the health care system and significantly contributes to the global epilepsy burden. As in many other resource-limited settings worldwide, health care professionals and patients with epilepsy in LAC countries face profound challenges due to a combination of factors, including high disease prevalence, stigmatization of epilepsy, disparities in access to care, limited resources, substantial treatment gaps, insufficient training opportunities for health care providers, and a diverse patient population with varying needs. This article presents an overview of the epidemiology of epilepsy and discusses the principal obstacles to epilepsy care and key contributors to the epilepsy diagnosis and treatment gap in the LAC region. We conclude by highlighting various initiatives across different LAC countries to improve epilepsy care in marginalized communities, listing strategies to mitigate treatment gaps and facilitate better health care access for patients with epilepsy by enhancing the epilepsy workforce.

Current management of SARS-CoV-2 infection in solid organ transplant recipients: Experience derived from an ESGICH-ESOT survey.

OBJECTIVE: Solid organ transplant (SOT) recipients have a poorer SARS-CoV-2 vaccine response and higher risk for COVID-19-associated complications. However, there is no consensus on the current management of COVID-19 and data on persistent COVID-19 rates in SOT recipients are lacking. METHODS: An electronic survey concerning the management of COVID-19 in SOT recipients was distributed among all members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) and of the European Society for Organ Transplantation (ESOT). Four major sections were covered: prevention, early COVID-19, late COVID-19, and persistent COVID-19. We developed a structured questionnaire including eight multiple-choice questions with branching logic in case of positive answers and three open-ended questions related to clinical practice. Questions were asked separately for lung and non-lung transplantation. RESULTS: Thirty-two physicians from 24 different centers participated. Most answers (n = 30) were provided by European physicians. Thirty of 32 (93.75%) physicians managed non-lung transplant recipients and 12 of 32 (33.3%) lung transplant recipients. There was a huge variability in practice regarding the treatment of COVID-19, and particularly noticeable when considering lung and non-lung transplant recipients. Main discordances included the use of nirmatrelvir alone or in combination therapy for early COVID-19, the use of immunomodulatory drugs other than steroids for late COVID-19, and the need for treating asymptomatic viral shedding in persistent COVID-19. There was more similarity in terms of prophylaxis recommendations. CONCLUSION: Despite a low number of respondents, this survey shows that there are many differences on how experts manage SARS-CoV-2 infections in SOT recipients.

Efficacy and safety of a preventive strategy against tuberculosis in liver transplantation recipients including the treatment of latent infection with moxifloxacin.

BACKGROUND: Preventive management of tuberculosis in liver transplantation (LT) is challenging due to difficulties in detecting and treating latent tuberculosis infection (LTBI). The aim of this study was to analyze the safety and efficacy of a screening strategy for LTBI with the inclusion of moxifloxacin as treatment. METHODS: We performed a retrospective single-center study of all LTs performed between 2016 and 2019 with a minimum 4-year follow-up and a standardized protocol for the evaluation of LTBI. RESULTS: Pretransplant LTBI screening was performed in 191/218 (87.6%) patients, and LTBI was diagnosed in 27.2% of them. Treatment for LTBI was administered to 71.2% of the patients and included moxifloxacin in 75.6% of the cases. After a median follow-up of 1628 days, no cases of active tuberculosis occurred among moxifloxacin-treated patients. The incidence of Clostridioides difficile (0.46 vs. 0.38 episodes/1000 transplant-days; p =  .8) and multidrug-resistant gram-negative bacilli infection (0 vs. 0.7 episodes per 1000 transplant-days; p =  .08) were not significantly higher in comparison to patients who did not receive moxifloxacin. CONCLUSION: A preventive strategy based on systematic LTBI screening and moxifloxacin treatment before LT in positive cases appears safe and effective in preventing the development of tuberculosis in LT recipients. However, our findings are limited by a small sample size; thus, larger studies are required to validate our observations.

Epilepsy and education: A case-control analysis of the impact of an intensive epilepsy training program on undergraduate medical students.

AIMS: To evaluate the knowledge, attitudes, and practical skills of students submitted to a 6-week intensive training in epilepsy compared to students without any training but mandatory neurology classes. METHODS: It is a case-control study. After completing a 6-week intensive Academic, Clinical, and Research Program in epilepsy, TUMSs answered a validated Knowledge Attitudes and Practices (KAP) questionnaire. The control group, composed of undergraduate students who shared the same age, academic year, and compulsory hours for learning about epilepsy as TUMSs, was also assessed through the KAP instrument. Answers from both groups were submitted to Fisher exact and the χ2 test to observe differences among groups. Descriptive statistics were also performed. RESULTS: TUMSs displayed better results in theoretical knowledge such as the definition and causes of epilepsy, and the application of paraclinical studies essential for diagnosing epilepsy. From their perspective, people with epilepsy encounter restricted opportunities for preserving their social life and employment and they are more prone to workplace accidents. They are convinced that facing epilepsy presents a notable risk due to the difficulties linked with diagnosis, considering epilepsy a challenging disease for general practitioners to identify and follow up. Likewise, they exhibited improvement in treatment adjustment and treatment monitoring of patients with epilepsy, mainly in pregnancy cases. Finally, they had greater knowledge about what to do when they witness a person experiencing a seizure. CONCLUSION: Our study showed that a 6-week intensive education program in epilepsy increased the knowledge and practical skills and changed the attitude toward patients with epilepsy of undergraduate students.

Nirmatrelvir/ritonavir for the treatment of immunocompromised adult patients with early-stage symptomatic COVID-19: A real-life experience.

Regardless of vaccination status, progression to severe coronavirus disease 2019 (COVID-19) is still a relevant cause of morbidity among immunocompromised patients. Despite the proven efficacy of nirmatrelvir/ritonavir (NMV/r), concerns remain regarding the potential for drug-to-drug interactions (DDIs) and the safety in this at-risk population. We aimed to evaluate the clinical outcomes of immunocompromised patients treated with NMV/r, as well as the occurrence of DDIs and treatment-emergent adverse events (TEAEs). This retrospective observational study included all the patients with some form of immunosuppression and laboratory-confirmed COVID-19 that received NMV/r at our center from April to August 2022. The main outcome was worsening of the clinical status (increase of ≥1 point from baseline in a validated clinical progression scale) by Days +7 and +28 after the initiation of therapy. Safety outcomes included the rates of any TEAE and potentially severe DDIs. We included 110 patients. Main causes of immunosuppression were hematological malignancy (58.2%) (mainly multiple myeloma [22.7%] and non-Hodgkin lymphoma [13.6%]), active chemotherapy (30.0%) and hematopoietic stem cell transplantation (14.5%). Clinical worsening by Days +7 and +28 was observed in four (3.6%) and five patients (4.5%), respectively. Only one patient had a positive SARS-CoV-2 polymerase chain reaction test at Day +28. At least one potentially severe DDI was observed in 56.4% of the patients. The rate of attributable TEAEs was 10.9%, although only two patients (1.8%) required premature discontinuation of NMV/r. Early initiation of NMV/r therapy should be considered in immunocompromised patients with COVID-19, with particular attention to interacting medications.

Production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in Klebsiella pneumoniae infection.

PURPOSE: To know whether the production of OXA-48 carbapenemase exerts an independent impact on the outcome of Klebsiella pneumoniae infection, once adjusted by clinical syndrome and baseline risk factors. METHODS: We performed a case-cohort study including 117 infectious episodes due to OXA-48-producing K. pneumoniae (OXA-48-Kp) and 117 episodes due to non-OXA-48-producing strains (non-OXA-48-Kp). Both groups were matched (1:1 ratio) by clinical syndrome (source of infection, preceding invasive procedures and indwelling devices, and associated bacteremia) and hospitalization ward at infection onset. Multivariate Cox regression was used to investigate the association between OXA-48-Kp infection and clinical cure by day 14 (primary outcome) and 30-day all-cause mortality (secondary outcome). RESULTS: Both study groups were well balanced regarding underlying conditions and comorbidity burden. Sepsis or septic shock were more frequent in OXA-48-Kp cases than non-OXA-48-Kp controls (41 [35.0%] vs. 17 [14.5%]; P-value < 0.0001). Clinical cure by day 14 was less commonly achieved in OXA-48-Kp cases (49 [41.9%] vs. 95 [81.2%]; P-value < 0.001), whereas 30-day all-cause mortality was higher (33 [28.2%] vs. 18 [15.4%]; P-value = 0.018). Multivariate analysis confirmed that OXA-48-Kp infection was independently associated with the lack of 14-day clinical cure (adjusted hazard ratio [aHR]: 0.45; 95% confidential interval [95%CI]: 0.29-0.70; P-value < 0.0001). A non-significant association was observed for 30-day all-cause mortality (aHR: 1.65; 95%CI: 0.92-2.94; P-value = 0.093). CONCLUSION: Our matched analysis suggests that the production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in K. pneumoniae infection as compared to episodes due to non-carbapenemase-producing strains.

A global survey on the attitudes of neurologists and psychiatrists about functional/psychogenic/dissociative/nonepileptic-seizures/attacks, in the search of its name.

PURPOSE: We conducted an observational study to investigate the opinions of neurologists and psychiatrists all around the world who are taking care of patients with seizures [epilepsy and functional seizures (FS)]. METHODS: Practicing neurologists and psychiatrists from around the world were invited to participate in an online survey. On 29th September 2022, an e-mail including a questionnaire was sent to the members of the International Research in Epilepsy (IR-Epil) Consortium. The study was closed on 1st March 2023. The survey, conducted in English, included questions about physicians' opinions about FS and anonymously collected data. RESULTS: In total, 1003 physicians from different regions of the world participated in the study. Both neurologists and psychiatrists identified "seizures" as their preferred term. Overall, the most preferred modifiers for "seizures" were "psychogenic" followed by "functional" by both groups. Most participants (57.9%) considered FS more difficult to treat compared to epilepsy. Both psychological and biological problems were considered as the underlying cause of FS by 61% of the respondents. Psychotherapy was considered the first treatment option for patients with FS (79.9%). CONCLUSION: Our study represents the first large-scale attempt of investigating physicians attitudes and opinions about a condition that is both frequent and clinically important. It shows that there is a broad spectrum of terms used by physicians to refer to FS. It also suggests that the biopsychosocial model has gained its status as a widely used framework to interpret and inform clinical practice on the management of patients.

A prospective study to identify preoperative serum parameters for spinal implant infection detected by sonication fluid culture.

PURPOSE: Low-virulent microorganisms identified on pedicle screws by sonication fluid culture (SFC) are an important cause of implant loosening. While sonication of explanted material improves the detection rate, the risk of contamination exists and no standardized diagnostic criteria for chronic low-grade spinal implant-related infection (CLGSII) are stablished. Besides, the role of serum C-reactive protein (CRP) and procalcitonin (PCT) in CLGSII has not been adequately investigated. METHODS: Blood samples were collected prior to implant removal. To increase sensitivity, the explanted screws were sonicated and processed separately. Patients exhibiting at least one positive SFC were classified in the infection group (loose criteria). To increase specificity, the strict criteria only considered multiple positive SFC (≥ 3 implants and/or ≥ 50% of explanted devices) as meaningful for CLGSII. Factors which might promote implant infection were also recorded. RESULTS: Thirty-six patients and 200 screws were included. Among them, 18 (50%) patients had any positive SFCs (loose criteria), whereas 11 (31%) patients fulfilled the strict criteria for CLGSII. Higher serum protein level was the most accurate marker for the preoperative detection of CLGSSI, exhibiting an area under the curve of 0.702 (loose criteria) and 0.819 (strict criteria) for the diagnosis of CLGSII. CRP only exhibited a modest accuracy, whereas PCT was not a reliable biomarker. Patient history (spinal trauma, ICU hospitalization and/or previous wound-related complications) increased the likelihood of CLGSII. CONCLUSION: Markers of systemic inflammation (serum protein level) and patient history should be employed to stratify preoperative risk of CLGSII and decide the best treatment strategy.

MindReader: Unsupervised Classification of Electroencephalographic Data.

Electroencephalogram (EEG) interpretation plays a critical role in the clinical assessment of neurological conditions, most notably epilepsy. However, EEG recordings are typically analyzed manually by highly specialized and heavily trained personnel. Moreover, the low rate of capturing abnormal events during the procedure makes interpretation time-consuming, resource-hungry, and overall an expensive process. Automatic detection offers the potential to improve the quality of patient care by shortening the time to diagnosis, managing big data and optimizing the allocation of human resources towards precision medicine. Here, we present MindReader, a novel unsupervised machine-learning method comprised of the interplay between an autoencoder network, a hidden Markov model (HMM), and a generative component: after dividing the signal into overlapping frames and performing a fast Fourier transform, MindReader trains an autoencoder neural network for dimensionality reduction and compact representation of different frequency patterns for each frame. Next, we processed the temporal patterns using a HMM, while a third and generative component hypothesized and characterized the different phases that were then fed back to the HMM. MindReader then automatically generates labels that the physician can interpret as pathological and non-pathological phases, thus effectively reducing the search space for trained personnel. We evaluated MindReader's predictive performance on 686 recordings, encompassing more than 980 h from the publicly available Physionet database. Compared to manual annotations, MindReader identified 197 of 198 epileptic events (99.45%), and is, as such, a highly sensitive method, which is a prerequisite for clinical use.

Abdominal normothermic regional perfusion in controlled donation after circulatory determination of death liver transplantation: Outcomes and risk factors for graft loss.

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques.

How to manage central venous catheter-related bloodstream infections due to Gram-negative bacilli?

PURPOSE OF REVIEW: The aim of this study was to review recent data evaluating the management of central venous catheter-related bloodstream infection due to Gram-negative bacilli (GNB). RECENT FINDINGS: The incidence of GNB catheter-related bloodstream infection (CRBSI) has been increasing considerably in the last years, and this has raised a concern due to the high reported rate of multidrug-resistant in these infections what poses a considerable challenge for effective treatment. However, there are no specific guidelines for the management of GNB-CRBSI and optimal treatment duration has not been clearly defined. Recent studies have shown that the risk for complications is clearly different to what is stablished for Staphylococcus aureus . Therefore, a short course of antibiotic therapy might be effective once the central venous catheter (CVC) has been removed and the monitoring complications through control blood cultures or echocardiography seem to be less helpful in GNB CRBSI. SUMMARY: The incidence of GNB CRBSI has been increasing considerably in the last years; this has raised a concern due to the high reported rate of MDR in these infections what poses a considerable challenge for effective treatment. However, there are no specific guidelines for the management of GNB-CRBSI and optimal treatment duration has not been clearly defined. Recent studies have shown that the risk for complications is clearly different to what is stablished for S. aureus . Therefore, a short course of antibiotic therapy might be effective once the CVC has been removed and the monitoring complications through control blood cultures or echocardiography seem to be less helpful in GNB-CRBSI.

Long-Term Outcomes of Perioperative Versus Neoadjuvant Chemotherapy for Resectable Colorectal Liver Metastases: An International Multicentre Propensity-Score Matched Analysis with Stratification by Contemporary Risk-Scoring.

BACKGROUND: There is still debate regarding the principal role and ideal timing of perioperative chemotherapy (CTx) for patients with upfront resectable colorectal liver metastases (CRLM). This study assesses long-term oncological outcomes in patients receiving neoadjuvant CTx only versus those receiving neoadjuvant combined with adjuvant therapy (perioperative CTx). METHODS: International multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010 and 2015. Characteristics and outcomes were compared before and after propensity score matching (PSM). Primary endpoints were long-term oncological outcomes, such as recurrence-free survival (RFS) and overall survival (OS). Furthermore, stratification by the tumour burden score (TBS) was applied. RESULTS: Of 967 patients undergoing hepatectomy, 252 were analysed, with a median follow-up of 45 months. The unmatched comparison revealed a bias towards patients with neoadjuvant CTx presenting with more high-risk patients (p = 0.045) and experiencing increased postoperative complications ≥Clavien-Dindo III (20.9% vs. 8%, p = 0.003). Multivariable analysis showed that perioperative CTx was associated with significantly improved RFS (hazard ratio [HR] 0.579, 95% confidence interval [CI] 0.420-0.800, p = 0.001) and OS (HR 0.579, 95% CI 0.403-0.834, p = 0.003). After PSM (n = 180 patients), the two groups were comparable regarding baseline characteristics. The perioperative CTx group presented with a significantly prolonged RFS (HR 0.53, 95% CI 0.37-0.76, p = 0.007) and OS (HR 0.58, 95% CI 0.38-0.87, p = 0.010) in both low and high TBS patients. CONCLUSIONS: When patients after resection of CRLM are able to tolerate additional postoperative CTx, a perioperative strategy demonstrates increased RFS and OS in comparison with neoadjuvant CTx only in both low and high-risk situations.

A pilot randomized controlled clinical trial of Transcranial Alternating Current Stimulation in patients with multifocal pharmaco-resistant epilepsy.

Transcranial Alternating Current Stimulation (tACS) is a promising noninvasive electrical stimulation therapy for neuropsychiatric diseases. Invasive neuromodulation using alternating current has been efficacious for drug-resistant epilepsy, but it is associated with surgical and medical complications. We aimed to explore the safeness and effectivity on seizure frequency reduction of two tACS protocols against placebo in patients with multifocal refractory epilepsy. This was a randomized, double-blinded, placebo-controlled clinical trial with 3-arm parallel-group (placebo, 30 min/2 mA daily sessions for 3 days [tACS-30], and 60 min/2 mA weekday sessions [tACS-60]). The main outcome was considered a change in reducing seizure frequency at 2 months after the intervention. Secondary outcomes were the apparition of any adverse effects during follow-up. At the second month, we observed a nonsignificant reduction in the seizure frequency in the placebo (7.3 ±â€¯40.4%, p > 0.05) and the tACS-60 (26 ±â€¯37.7%, p > 0.05). While the tACS-30 group showed a nonsignificant increase in seizure frequency (63.6 ±â€¯155.3%, p > 0.05). No changes were statistically different from the placebo group. Otherwise, participants experienced only minor adverse events - the most common being an initial local transient tingling sensation (21%). This pilot study of tACS raises no severe safety issues, but provides negligible evidence for efficacy using this brief treatment protocol. Therefore, more studies are warranted testing different parameters to further verify the safety and effectivity of tACS in multifocal epilepsy.

Intraoperative neurophysiological monitoring in Latin America: A bibliometric analysis.

PURPOSE: Intraoperative Neurophysiological Monitoring (IOMM) has been used worldwide in the attempt to reduce postsurgical neurological deficits, however, most of the publications are from developed countries. There is a global bibliometric analysis of IOMN in spinal surgery, however, the contribution of Latin America (LA) is not mentioned. The aim of this study is to describe scientific productivity, patterns of publications, and thematic trends of IONM in LA. METHODS: Data was collected using Scopus database, by searching scientific articles with LA affiliation, using 18 keywords. We excluded duplicates, not original articles, reviews, surveys, and articles not related to humans. Articles were analyzed and classified as follows: year of publication, language of the original document, journals metrics, country, IONM modality, etiology, location of surgery, medical specialties, and outcome. Descriptive statistics were used. RESULTS: We obtained 8,699 scientific articles of which 41 scientific articles from 7 LA countries were selected. Mexico has the highest number of publications. In most countries, supratentorial location showed the highest frequency. Somatosensory evoked potentials and electrocorticography were the most performed modalities. Neurosurgery was the most involved specialty of our 41 scientific articles, and 95.1% of these publications concluded that IONM is useful to guide surgical procedures. CONCLUSIONS: Mexico and Brazil have led IONM publications in LA. The lower reference in publications of visual evoked potentials and brainstem auditory evoked potentials IONM modalities, could be considered in the future to boost tailored research in LA.

Eradication of Staphylococcus aureus Post-Sternotomy Mediastinitis Following the Implementation of Universal Preoperative Nasal Decontamination With Mupirocin: An Interrupted Time-Series Analysis.

BACKGROUND: Although presurgical nasal decontamination with mupirocin (NDM) has been advocated as a measure for preventing postsurgical mediastinitis (PSM) due to Staphylococcus aureus, this strategy is not universally recommended due to lack of robust supporting evidence. We aimed to evaluate the role of preoperative NDM in the annual incidence of S. aureus PSM at our institution. METHODS: An interrupted time-series analysis, with an autoregressive error model, was applied to our single-center cohort by comparing preintervention (1990-2003) and postintervention (2005-2018) periods. Logistic regression was performed to analyze risk factors for S. aureus PSM. RESULTS: 12 236 sternotomy procedures were analyzed (6370 [52.1%] and 5866 [47.9%] in the pre- and postintervention periods, respectively). The mean annual percentage adherence to NDM estimated over the postintervention period was 90.2%. Only 4 of 127 total cases of S. aureus PSM occurred during the 14-year postintervention period (0.68/1000 sternotomies vs 19.31/1000 in the preintervention period; P < .0001). Interrupted time-series analysis demonstrated a statistically significant annual reduction in S. aureus PSM of -9.85 cases per 1000 sternotomies (-13.17 to -6.5; P < .0001) in 2005, with a decreasing trend maintained over the following 5 years and an estimated relative reduction of 84.8% (95% confidence interval [CI], 89.25-74.09%). Chronic obstructive pulmonary disease was the single independent risk factor for S. aureus PSM (odds ratio, 3.7; 95% CI, 1.72-7.93) and was equally distributed in patients undergoing sternotomy during pre- or postintervention periods. CONCLUSIONS: Our experience suggests the implementation of preoperative NDM significantly reduces the incidence of S. aureus PSM.

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial.

BACKGROUND: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. METHODS: A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. RESULTS: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). CONCLUSIONS: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338.

Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders.

BACKGROUND: Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. OBJECTIVE: We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson's disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. METHODS: Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. RESULTS: Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson's disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). CONCLUSION: All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.

Efficacy of ß-lactam/ß-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

BACKGROUND: Whether active therapy with ß-lactam/ß-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/µL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

Epilepsy diagnosis based on one unprovoked seizure and ≥60% risk. A systematic review of the etiologies.

BACKGROUND: According to the International League Against Epilepsy (ILAE) criteria, epilepsy can be diagnosed after one unprovoked (or reflex) seizure when there is a ≥60% of seizure recurrence in the next decade. The application of this diagnostic criterion, however, is challenging because the risk of recurrence based on different etiologies is not easily retrievable from the literature. OBJECTIVE: To assess etiologies that permit a diagnosis of epilepsy after a single unprovoked seizure. METHODS: We conducted a systematic review of the literature search using PubMed, Scopus, and Cochrane library from January 1950 to December 2020 with the keywords: recurrence, risk of recurrence, absolute risk, risk ratio, risk, seizures, epilepsy, structural, infectious, metabolic, immune, and genetic. We included articles that reported estimates of risks of a subsequent unprovoked seizure. Etiologies were categorized according to the ILAE epilepsy classification. The quality of the evidence was evaluated with PRISMA. Descriptive statistics were used. RESULTS: A total of 25,044 articles resulted from searching three databases. After authors removed duplicates, 18,911 articles remained. We screened by title and abstract, 40 articles were reviewed and finally, two articles were included. The mean follow-up was 8 years and the mean for a risk to present a subsequent unprovoked seizure was 66.6% and included structural etiologies as stroke, traumatic brain injury, cavernous malformation, arteriovenous malformation, and neuroinfections (unspecified agents). Study quality characteristics are classified with low strength of evidence and moderate-quality cohort. CONCLUSIONS: We found that stroke, traumatic brain injury, cavernous or arteriovenous malformations, and unspecified CNS infections can meet the epilepsy diagnosis after one unprovoked seizure based on low strength of evidence and moderate quality of cohorts.