Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn's disease: The HEAL study from GETECCU.

BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. METHODS: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. CONCLUSION: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

Allocation of the household food budget among shopping basket items: How is it influenced by promotions?

Retailers have been using promotion as a differentiation strategy that influences consumers' expenditures and their shopping basket budgetary allocation. This study assessed the effect of retail promotions on total shopping basket expenditure and determined whether promotions provoke a reallocation of the shopping budget. The analysis was performed on a chain of supermarkets in Catalonia, Spain using a consumer scanner data set from Kantar Worldpanel for 2017. The methodological approach had two steps: prediction of the effect of promotion on household expenditures using an expenditure regression model and estimation of the promotion own- and cross-effect using the censored Exact Affine Stone Index. Promotion had a positive own-effect and mostly a negative asymmetric cross-effect, implying a small but significant budget reallocation.

Gypsum Cave Biofilm Communities are Strongly Influenced by Bat- And Arthropod-Related Fungi.

The Gypsum Karst of Sorbas, Almeria, southeast Spain, includes a few caves whose entrances are open and allow the entry and roosting of numerous bats. Caves are characterized by their diversity of gypsum speleothems, such as stalactites, coralloids, gypsum crusts, etc. Colored biofilms can be observed on the walls of most caves, among which the Covadura and C3 caves were studied. The objective was to determine the influence that bat mycobiomes may have on the fungal communities of biofilms. The results indicate that the fungi retrieved from white and yellow biofilms in Covadura Cave (Ascomycota, Mortierellomycota, Basidiomycota) showed a wide diversity, depending on their location, and were highly influenced by the bat population, the guano and the arthropods that thrive in the guano, while C3 Cave was more strongly influenced by soil- and arthropod-related fungi (Ascomycota, Mortierellomycota), due to the absence of roosting bats.

A comprehensive, predictive mortality score for patients with bloodstream infections (PROBAC): a prospective, multicentre cohort study.

OBJECTIVES: Bloodstream infections (BSI) are an important cause of mortality, although they show heterogeneity depending on patients and aetiological factors. Comprehensive and specific mortality scores for BSI are scarce. The objective of this study was to develop a mortality predictive score in BSI based on a multicentre prospective cohort. METHODS: A prospective cohort including consecutive adults with bacteraemia recruited between October 2016 and March 2017 in 26 Spanish hospitals was randomly divided into a derivation cohort (DC) and a validation cohort (VC). The outcome was all-cause 30-day mortality. Predictors were assessed the day of blood culture growth. A logistic regression model and score were developed in the DC for mortality predictors; the model was applied to the VC. RESULTS: Overall, 4102 patients formed the DC and 2009 the VC. Mortality was 11.8% in the DC and 12.34% in the CV; the patients and aetiological features were similar for both cohorts. The mortality predictors selected in the final multivariate model in the DC were age, cancer, liver cirrhosis, fatal McCabe underlying condition, polymicrobial bacteraemia, high-risk aetiologies, high-risk source of infection, recent use of broad-spectrum antibiotics, stupor or coma, mean blood pressure <70 mmHg and PaO2/FiO2 ≤ 300 or equivalent. Mortality in the DC was <2% for ≤2 points, 6%-14% for 3-7 points, 26%-45% for 8-12 points and ≥60% for ≥13 points. The predictive score had areas under the receiving operating curves of 0.81 (95% CI 0.79-0.83) in the DC and 0.80 (0.78-0.83) in the VC. CONCLUSIONS: A 30 day mortality predictive score in BSI with good discrimination ability was developed and internally validated.

Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here 138 ITP patients (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range, IQR, 56-80 years). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166 months). The median number of therapies prior to fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%) and intravenous immunoglobulins (IVIG) (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month prior to treatment initiation. 79.0% of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 x 109 /L). Eighty-three patients (60.1%) received fostamatinib monotherapy achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21 days). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1-2, the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Retrospective study of germline variants in patients with hereditary melanoma study criteria in a real clinical practice setting.

INTRODUCTION: Five to twelve percent of melanomas show aggregation of melanomas or other related tumors within the same family or individual. Genes such as CDKN2A, or BAP1, among others, have been involved in this condition. MATERIAL AND METHODS: Retrospective descriptive study that includes patients from Cruces University Hospital (2016-2023) who met any of the following criteria: presence of two or more melanomas (1), or a melanoma and a pancreatic cancer (2) in the same individual; presence of a melanoma in an individual and one or more first- or second-degree relatives with melanoma or pancreatic cancer (3); first- or second-degree relationship with an individual with a known deleterious variant in genes related to melanoma predisposition (4); or incidental discovery of deleterious variants in genes related to predisposition to melanoma, within hereditary cancer panels carried out for reasons other than melanoma (5). RESULTS: 59 families were included (69 patients; 63.8% women), of which 8.5% (13% of patients) presented pathogenic/likely pathogenic variants (PV/LPV) in CDKN2A (6% of families and patients, excluding criteria 4 and 5), and 1.7% of families (1.4% of patients) presented PV/LPV in BAP1, BRCA2 and TERF2IP. DISCUSSION AND CONCLUSIONS: The frequencies of PV/LPV in CDKN2A are similar to those previously described. This study could contribute to the knowledge of the characteristics of patients who meet genetic study criteria for hereditary melanoma, in a setting of real clinical practice.

Data analysis plan of the OECD PaRIS survey: leveraging a multi-level approach to analyse data collected from people living with chronic conditions and their primary care practices in 20 countries.

OBJECTIVE: In view of the increasing number of people with (multiple) chronic conditions, the Organisation for Economic Co-operation and Development (OECD) initiated the International Survey of People Living with Chronic Conditions (PaRIS survey), which aims to provide insight in patient-reported outcomes and experiences of chronic care provided by primary care practices to support policy development. The objective of this research note is to describe the structure of the data, collected in the PaRIS survey and how the data will be analysed in a multilevel approach for cross-country comparison. ANALYSIS PLAN: The data structure of the PaRIS survey represents three levels: countries/health systems, primary care practices and patients. Multilevel analysis is used because of its accuracy in estimating country-level outcomes, its flexibility in modelling relationships, and its opportunities in connecting to relevant policy questions. Country-level outcomes will be estimated to facilitate cross-country comparison and (future) within-country comparison over time. Characteristics of patients that potentially explain variation in patient-reported outcomes and experiences can be linked to primary care practice and country/health system characteristics. This makes it possible to address policy-relevant questions relating, e.g., to the impact of chronic care management on patients with a specific chronic condition.

A clinical practice guideline for the management of the foot and ankle in rheumatoid arthritis.

Rheumatoid arthritis causes progressive joint destruction in the long term, causing a deterioration of the foot and ankle. A clinical practice guideline has been created with the main objective of providing recommendations in the field of podiatry for the conservative management of rheumatoid arthritis. Thus, healthcare professionals involved in foot care of adults with rheumatoid arthritis will be able to follow practical recommendations. A clinical practice guideline was created including a group of experts (podiatrists, rheumatologists, nurses, an orthopaedic surgeon, a physiotherapist, an occupational therapist and patient with rheumatoid arthritis). Methodological experts using GRADE were tasked with systematically reviewing the available scientific evidence and developing the information which serves as a basis for the expert group to make recommendations. Key findings include the efficacy of chiropody in alleviating hyperkeratotic lesions and improving short-term pain and functionality. Notably, custom and standardized foot orthoses demonstrated significant benefits in reducing foot pain, enhancing physical function, and improving life quality. Therapeutic footwear was identified as crucial for pain reduction and mobility improvement, emphasizing the necessity for custom-made options tailored to individual patient needs. Surgical interventions were recommended for cases which were non-responsive to conservative treatments, aimed at preserving foot functionality and reducing pain. Moreover, self-care strategies and education were underscored as essential components for promoting patient independence and health maintenance. A series of recommendations have been created which will help professionals and patients to manage podiatric pathologies derived from rheumatoid arthritis.

Automated facial recognition system using deep learning for pain assessment in adults with cerebral palsy.

Objective: Assessing pain in individuals with neurological conditions like cerebral palsy is challenging due to limited self-reporting and expression abilities. Current methods lack sensitivity and specificity, underlining the need for a reliable evaluation protocol. An automated facial recognition system could revolutionize pain assessment for such patients.The research focuses on two primary goals: developing a dataset of facial pain expressions for individuals with cerebral palsy and creating a deep learning-based automated system for pain assessment tailored to this group. Methods: The study trained ten neural networks using three pain image databases and a newly curated CP-PAIN Dataset of 109 images from cerebral palsy patients, classified by experts using the Facial Action Coding System. Results: The InceptionV3 model demonstrated promising results, achieving 62.67% accuracy and a 61.12% F1 score on the CP-PAIN dataset. Explainable AI techniques confirmed the consistency of crucial features for pain identification across models. Conclusion: The study underscores the potential of deep learning in developing reliable pain detection systems using facial recognition for individuals with communication impairments due to neurological conditions. A more extensive and diverse dataset could further enhance the models' sensitivity to subtle pain expressions in cerebral palsy patients and possibly extend to other complex neurological disorders. This research marks a significant step toward more empathetic and accurate pain management for vulnerable populations.

Imbalance of SARS-CoV-2-specific CCR6+ and CXCR3+ CD4+ T cells and IFN-γ + CD8+ T cells in patients with Long-COVID.

Long-COVID (LC) is characterised by persistent symptoms for at least 3 months after acute infection. A dysregulation of the immune system and a persistent hyperinflammatory state may cause LC. LC patients present differences in activation and exhaustion states of innate and adaptive compartments. Different T CD4+ cell subsets can be identified by differential expression of chemokine receptors (CCR). However, changes in T cells with expression of CCRs such as CCR6 and CXCR3 and their relationship with CD8+ T cells remains unexplored in LC. Here, we performed unsupervised analysis and found CCR6+ CD4+ subpopulations enriched in COVID-19 convalescent individuals upon activation with SARS-CoV-2 peptides. SARS-CoV-2 specific CCR6+ CD4+ are decreased in LC patients, whereas CXCR3+ CCR6- and CCR4+ CCR6- CD4+ T cells are increased. LC patients showed lower IFN-γ-secreting CD8+ T cells after stimulation with SARS-CoV-2 Spike protein. This work underscores the role of CCR6 in the pathophysiology of LC.

Assessment of Changes in the Outcome of Autogenous Tooth Grafts Over Time: A Clinical Study Evaluating Periodontal Healing in Bone Defects After Lower Third Molar Removal.

BACKGROUND: The removal of impacted lower third molars (ILTMs) is associated with bone defects in the distal area of second molars. Different methods have been described to minimize these defects. PURPOSE: The primary objective was to assess changes in probing depth (PD) over time (up to 36 months) between test (grafted) and control (ungrafted) groups; the graft was obtained from the extracted ILTM. STUDY DESIGN, SETTING, SAMPLE: This split-mouth randomized clinical trial was conducted at the Postgraduate Course in Oral Surgery of the Faculty of Dentistry of the Complutense University of Madrid. Adult patients requiring bilateral ILTM extraction with adjacent second molars were recruited, excluding pregnant/lactating women, patients in treatment with nonsteroidal anti-inflammatory drugs and patients with periodontal diseases. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The predictor variable was the graft technique. The bone defect after ILTM removal was treated with autogenous tooth graft (ATG) in the test group, leaving the control group ungrafted. MAIN OUTCOME VARIABLE: PD on the distobuccal, distomedial, and distolingual surfaces was recorded in both groups and averaged at baseline (T0), 3 (T1), 6 (T2), and 36 months (T3) postoperatively. COVARIATES: Sex, age, surgical time, ILTM situation and position between groups were assessed. ANALYSES: ANOVA repeated measures for comparisons between groups and the Friedman test for comparisons within the groups over time were applied. Statistical significance was established with a confidence interval of 95% (P < .05). RESULTS: The sample comprised 22 patients (6 males, 16 females) with a mean age of 21.68 ± 2.19 years; 44 ILTM extractions were performed. Statistically significant differences in PD average were found between groups (P < .001, 95% confidence interval) at 3 (1.63 ± 0.29), 6 (1.76 ± 0.3), and 36 months (1.74 ± 0.36). Reductions from T0 to T3 of 2.74 ± 0.28 (P < .001) and 0.54 ± 0.3 (P = .43) were observed in test and control groups, respectively. CONCLUSION AND RELEVANCE: ATG placed on the distal surface of lower second molars and almost completely filling the extraction socket improved PD 3, 6 and 36 months after ILTM. Furthermore, no significant changes in PD were observed over time; no major complications occurred. ATG appears to be a viable alternative graft material for this procedure.

Efficacy of Co-Crystal of Tramadol-Celecoxib (CTC) in Patients with Acute Moderate-to-Severe Pain: A Pooled Analysis of Data from Two Phase 3 Randomized Clinical Trials.

BACKGROUND AND OBJECTIVES: New acute pain medications are needed that provide effective analgesia while minimizing side effects and opioid exposure. Clinical trials of co-crystal of tramadol-celecoxib (CTC) have demonstrated an improved benefit/risk profile versus tramadol or celecoxib alone. We pooled data from two phase 3 clinical trials to evaluate the efficacy of CTC 200 mg twice daily (BID) in acute moderate-to-severe pain. METHODS: Efficacy data were pooled from STARDOM1 [acute pain following oral surgery (NCT02982161)] and ESTEVE-SUSA-301 [acute pain following bunionectomy (NCT03108482)]. The primary efficacy outcome was sum of pain intensity difference from 0 to 48 h (SPID0-48). RESULTS: A total of 344 patients received CTC 200 mg BID, 342 received tramadol 50 or 100 mg four times a day, 181 received celecoxib 100 mg BID, and 172 received placebo. The least-squares mean difference in SPID0-48 was -21.8 (p = 0.002) for CTC versus tramadol and -72.8 (p < 0.001) for CTC versus placebo. A similar pattern of SPID0-48 was observed with CTC versus comparator whether patients had moderate or severe pain at baseline. Reduction in pain intensity was faster and reached mild intensity earlier with CTC versus comparators. Patients were significantly (p ≤ 0.005) less likely to receive rescue medication within 4 or 48 h with CTC compared with tramadol or placebo. CONCLUSIONS: This pooled analysis reinforces the efficacy profile of CTC versus tramadol and, given that CTC permits lower daily tramadol dosing and thereby reduces unnecessary opioid use, this highlights its improved benefit/risk profile and its potential for the management of moderate-to-severe pain.

Environmental Factors Influencing Metal Concentrations in Scomber colias Along the Canary Islands.

A total of 140 specimens of Scomber colias were collected from the Canary archipelago waters during the first semester of 2021, with 20 samples from each of the seven main islands. After analyzing the concentrations of metals (Al, Zn, Cd, Pb, Fe, and Cu) with ICP-OES, significant variations were observed among islands, with specimens from Tenerife and Gran Canaria containing higher levels of Al, Cd, and Pb, while those from Lanzarote and Fuerteventura had elevated levels of Zn, Fe, and Cu. These differences are probably related to greater anthropogenic activity around Tenerife and Gran Canaria coasts, leading to higher pollution levels, and the influence of Saharan dust and African upwelling on Lanzarote and Fuerteventura, enriching the waters with nutrients. Specific management strategies to mitigate marine pollution and continuous monitoring are crucial to safeguard marine ecosystems and to ensure food security.

MR Imaging Findings in Anti-Leucine-Rich Glioma Inactivated Protein 1 Encephalitis: A Systematic Review and Meta-analysis.

BACKGROUND: Antibodies against leucine-rich glioma inactivated protein 1 (LGI1) constitute a common form of autoimmune encephalitis. On MR imaging, it may show T2 FLAIR hyperintensities of the medial temporal lobe (T2 FLAIR-MTL), involve the basal ganglia, or be unremarkable. PURPOSE: We performed a systematic review and meta-analysis to obtain prevalence estimates of abnormal findings on MR imaging in anti-LGI1 encephalitis. A human brain map of the LGI1 microarray gene expression was derived from the Allen Human Brain Atlas. DATA SOURCES: PubMed and Web of Science were searched with the terms "LGI1" and "encephalitis" from inception to April 7, 2022. STUDY SELECTION: Thirty-one research publications, encompassing case series and retrospective cohort and case-control studies, with >10 patients with anti-LGI1 encephalitis and MR imaging data were included. DATA ANALYSIS: Pooled prevalence estimates were calculated using Freeman-Tukey double-arcsine transformation. Meta-analysis used DerSimonian and Laird random effects models. DATA SYNTHESIS: Of 1318 patients in 30 studies, T2 FLAIR-MTL hyperintensities were present in 54% (95% CI, 0.48-0.60; I2 = 76%). Of 394 patients in 13 studies, 27% showed bilateral (95% CI, 0.19-0.36; I2 = 71%) and 24% unilateral T2 FLAIR-MTL abnormalities (95% CI, 0.17-0.32; I2 = 61%). Of 612 patients in 15 studies, basal ganglia abnormalities were present in 10% (95% CI, 0.06-0.15; I2 = 67%). LGI1 expression was highest in the amygdala, hippocampus, and caudate nucleus. LIMITATIONS: Only part of the spectrum of MR imaging abnormalities in anti-LGI1 encephalitis could be included in a meta-analysis. MR imaging findings were not the main outcomes in most studies, limiting available information. I2 values ranged from 62% to 76%, representing moderate-to-large heterogeneity. CONCLUSIONS: T2 FLAIR-MTL hyperintensities were present in around one-half of patients with anti-LGI1. The prevalence of unilateral and bilateral presentations was similar, suggesting unilaterality should raise the suspicion of this disease in the appropriate clinical context. Around 10% of patients showed basal ganglia abnormalities, indicating that special attention should be given to this region. LGI1 regional expression coincided with the most frequently reported abnormal findings on MR imaging. Regional specificity might be partially determined by expression levels of the target protein.

Effect of early vs. delayed extubation on functional outcome among patients with acute ischemic stroke treated with endovascular thrombectomy under general anesthesia: the prospective, randomized controlled EDESTROKE trial study protocol.

BACKGROUND: Recent meta-analyses and randomized studies have shown that among patients with acute ischemic stroke undergoing endovascular thrombectomy, general anesthesia with mechanical ventilation is associated with better functional status compared to local anesthesia and sedation, and they recommend its use. But once the procedure is completed, when is the optimal moment for extubation? Currently, there are no guidelines recommending the optimal moment for extubation. Prolonged mechanical ventilation time could potentially be linked to increased complications such as pneumonia or disturbances in cerebral blood flow due to the vasodilatation produced by most anesthetic drugs. However, premature extubation in a patient who has suffered a stroke could led to complications such as agitation, disorientation, abolished reflexes, sudden fluctuations in blood pressure, alterations in cerebral blood flow, respiratory distress, bronchial aspiration, and the need for reintubation. We therefore designed a randomized study hypothesizing that early compared with delayed extubation is associated with a better functional outcome 3 months after endovascular thrombectomy treatment under general anesthesia for acute ischemic stroke. METHODS: This investigator-initiated, single-center, prospective, parallel, evaluated blinded, superiority, randomized controlled trial will include 178 patients with a proximal occlusion of the anterior circulation treated with successful endovascular thrombectomy (TICI 2b-3) under general anesthesia. Patients will be randomly allocated to receive early (< 6 h) or delayed (6-12 h) extubation after the procedure. The primary outcome measure is functional independence (mRS of 0-2) at 90 days, measured with the modified Rankin Score (mRS), ranging from 0 (no symptoms) to 6 (death). DISCUSSION: This will be the first trial to compare the effect of mechanical ventilation duration (early vs delayed extubation) after satisfactory endovascular thrombectomy for acute ischemic stroke under general anesthesia. TRIAL REGISTRATION: The study protocol was approved April 11, 2023, by the by the Santiago-Lugo Research Ethics Committee (CEI-SL), number 2023/127, and was registered into the clinicaltrials.gov clinical trials registry with No. NCT05847309. Informed consent is required. Participant recruitment begins on April 18, 2023. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

Diagnostic differences in high-resolution esophageal motility in a large Mexican cohort based on geographic distribution.

High-resolution esophageal manometry [HRM] has become the gold standard for the evaluation of esophageal motility disorders. It is unclear whether there are HRM differences in diagnostic outcome based on regional or geographic distribution. The diagnostic outcome of HRM in a diverse geographical population of Mexico was compared and determined if there is variability in diagnostic results among referral centers. Consecutive patients referred for HRM during 2016-2020 were included. Four major referral centers in Mexico participated in the study: northeastern, southeastern, and central (Mexico City, two centers). All studies were interpreted by experienced investigators using Chicago Classification 3 and the same technology. A total of 2293 consecutive patients were included. More abnormal studies were found in the center (61.3%) versus south (45.8%) or north (45.2%) P < 0.001. Higher prevalence of achalasia was noted in the south (21.5%) versus center (12.4%) versus north (9.5%) P < 0.001. Hypercontractile disorders were more common in the north (11.0%) versus the south (5.2%) or the center (3.6%) P.001. A higher frequency of weak peristalsis occurred in the center (76.8%) versus the north (74.2%) or the south (69.2%) P < 0.033. Gastroesophageal junction obstruction was diagnosed in (7.2%) in the center versus the (5.3%) in the north and (4.2%) in the south p.141 (ns). This is the first study to address the diagnostic outcome of HRM in diverse geographical regions of Mexico. We identified several significant diagnostic differences across geographical centers. Our study provides the basis for further analysis of the causes contributing to these differences.

miRNome profiling of extracellular vesicles in severe COVID-19 patients and identification of predictors of mortality.

BACKGROUND: Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. METHODS: A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. RESULTS: Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. CONCLUSION: : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.

Severe Presentation of Mpox With Skin, Lung and Pleural Involvement in a Non-HIV Infected Kidney Transplant Recipient.

Monkeypox (mpox) is an orthopoxviral zoonotic disease with a similar, but less severe, clinical presentation as smallpox. However, immunocompromised patients such as solid organ transplant recipients are at higher risk of developing severe forms of the disease. Herein, we describe the case of a 43 years-old female kidney transplant recipient that manifested severe skin ulcers alongside nodular lung opacities and pleural effusion attributed directly to the Monkeypox virus. Notwithstanding the initiation of early treatment with tecovirimat, a satisfactory response was not achieved until a reduction in immunosuppression to everolimus monotherapy, coupled with the transition to cidofovir for antiviral treatment. In conclusion, mpox has the potential to produce a severe form of systemic infection in individuals who have undergone solid organ transplantation, demanding a meticulous approach involving sequential antiviral treatment and modifications to immunosuppressive regimens in order to achieve complete healing.