Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps.

Since its introduction in the human population, SARS-CoV-2 has evolved into multiple clades, but the events in its intrahost diversification are not well understood. Here, we compare three-dimensional (3D) self-organized neural haplotype maps (SOMs) of SARS-CoV-2 from thirty individual nasopharyngeal diagnostic samples obtained within a 19-day interval in Madrid (Spain), at the time of transition between clades 19 and 20. SOMs have been trained with the haplotype repertoire present in the mutant spectra of the nsp12- and spike (S)-coding regions. Each SOM consisted of a dominant neuron (displaying the maximum frequency), surrounded by a low-frequency neuron cloud. The sequence of the master (dominant) neuron was either identical to that of the reference Wuhan-Hu-1 genome or differed from it at one nucleotide position. Six different deviant haplotype sequences were identified among the master neurons. Some of the substitutions in the neural clouds affected critical sites of the nsp12-nsp8-nsp7 polymerase complex and resulted in altered kinetics of RNA synthesis in an in vitro primer extension assay. Thus, the analysis has identified mutations that are relevant to modification of viral RNA synthesis, present in the mutant clouds of SARS-CoV-2 quasispecies. These mutations most likely occurred during intrahost diversification in several COVID-19 patients, during an initial stage of the pandemic, and within a brief time period.

Biosensor capability of the endometrium is mediated in part, by altered miRNA cargo from conceptus-derived extracellular vesicles.

We tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri-implantation period of pregnancy. We transferred Bos taurus taurus embryos of different origin, in vivo (high developmental potential (IV)), in vitro (intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), into Bos taurus indicus recipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus-conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response to in vivo versus in vitro and in vivo versus cloned conceptuses (1153 and 334DEGs respectively) with limited differences between in vitro Vs cloned conceptuses (36 DEGs). The miRNA cargo contained in conceptus-derived EVs was similar between all three groups (426 miRNA in common). Only 8 miRNAs were different between in vivo and cloned conceptuses, while only 6 miRNAs were different between in vivo and in vitro-derived conceptuses. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changed the proteomic content of target cells (96 and 85, respectively) of which mRNAs are altered in the endometrium in vivo (PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri-implantation period of pregnancy.

Cardiac stasis imaging, stroke, and silent brain infarcts in patients with nonischemic dilated cardiomyopathy.

Cardioembolic stroke is one of the most devastating complications of nonischemic dilated cardiomyopathy (NIDCM). However, in clinical trials of primary prevention, the benefits of anticoagulation are hampered by the risk of bleeding. Indices of cardiac blood stasis may account for the risk of stroke and be useful to individualize primary prevention treatments. We performed a cross-sectional study in patients with NIDCM and no history of atrial fibrillation (AF) from two sources: 1) a prospective enrollment of unselected patients with left ventricular (LV) ejection fraction <45% and 2) a retrospective identification of patients with a history of previous cardioembolic neurological event. The primary end point integrated a history of ischemic stroke or the presence intraventricular thrombus, or a silent brain infarction (SBI) by imaging. From echocardiography, we calculated blood flow inside the LV, its residence time (TR) maps, and its derived stasis indices. Of the 89 recruited patients, 18 showed a positive end point, 9 had a history of stroke or transient ischemic attack (TIA) and 9 were diagnosed with SBIs in the brain imaging. Averaged TR, [Formula: see text] performed well to identify the primary end point [AUC (95% CI) = 0.75 (0.61-0.89), P = 0.001]. When accounting only for identifying a history of stroke or TIA, AUC for [Formula: see text] was 0.92 (0.85-1.00) with odds ratio = 7.2 (2.3-22.3) per cycle, P < 0.001. These results suggest that in patients with NIDCM in sinus rhythm, stasis imaging derived from echocardiography may account for the burden of stroke.NEW & NOTEWORTHY Patients with nonischemic dilated cardiomyopathy (NIDCM) are at higher risk of stroke than their age-matched population. However, the risk of bleeding neutralizes the benefit of preventive oral anticoagulation. In this work, we show that in patients in sinus rhythm, the burden of stroke is related to intraventricular stasis metrics derived from echocardiography. Therefore, stasis metrics may be useful to personalize primary prevention anticoagulation in these patients.

Puzzles, challenges, and information reservoir of SARS-CoV-2 quasispecies.

Upon the emergence of SARS-CoV-2 in the human population, it was conjectured that for this coronavirus the dynamic intra-host heterogeneity typical of RNA viruses would be toned down. Nothing of this sort is observed. Here we review the main observations on the complexity and diverse composition of SARS-CoV-2 mutant spectra sampled from infected patients, within the framework of quasispecies dynamics. The analyses suggest that the information provided by myriads of genomic sequences within infected individuals may have a predictive value of the genomic sequences that acquire epidemiological relevance. Possibilities to reconcile the presence of broad mutant spectra in the large RNA coronavirus genome with its encoding a 3' to 5' exonuclease proofreading-repair activity are considered. Indeterminations in the behavior of individual viral genomes provide a benefit for the survival of the ensemble. We propose that this concept falls in the domain of "stochastic thinking," a notion that applies also to cellular processes, as a means for biological systems to face unexpected needs.

Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools.

In the course of experiments aimed at deciphering the inhibition mechanism of mycophenolic acid and ribavirin in hepatitis C virus (HCV) infection, we observed an inhibitory effect of the nucleoside guanosine (Gua). Here, we report that Gua, and not the other standard nucleosides, inhibits HCV replication in human hepatoma cells. Gua did not directly inhibit the in vitro polymerase activity of NS5B, but it modified the intracellular levels of nucleoside di- and tri-phosphates (NDPs and NTPs), leading to deficient HCV RNA replication and reduction of infectious progeny virus production. Changes in the concentrations of NTPs or NDPs modified NS5B RNA polymerase activity in vitro, in particular de novo RNA synthesis and template switching. Furthermore, the Gua-mediated changes were associated with a significant increase in the number of indels in viral RNA, which may account for the reduction of the specific infectivity of the viral progeny, suggesting the presence of defective genomes. Thus, a proper NTP:NDP balance appears to be critical to ensure HCV polymerase fidelity and minimal production of defective genomes.

Fluoride anodic films on stainless-steel fomites to reduce transmission infections.

The growing concern arising from viruses with pandemic potential and multi-resistant bacteria responsible for hospital-acquired infections and outbreaks of food poisoning has led to an increased awareness of indirect contact transmission. This has resulted in a renewed interest to confer antimicrobial properties to commonly used metallic materials. The present work provides a full characterization of optimized fluoride anodic films grown in stainless steel 304L as well as their antimicrobial properties. Antibacterial tests show that the anodic film, composed mainly of chromium and iron fluorides, reduces the count and the percentage of the area covered by 50% and 87.7% for Pseudomonas aeruginosa and Stenotrophomonas maltophilia, respectively. Virologic tests show that the same treatment reduces the infectivity of the coronavirus HCoV-229E-GFP, in comparison with the non-anodized stainless steel 304L.IMPORTANCEThe importance of environmental surfaces as a source of infection is a topic of particular interest today, as many microorganisms can survive on these surfaces and infect humans through direct contact. Modification of these surfaces by anodizing has been shown to be useful for some alloys of medical interest. This work evaluates the effect of anodizing on stainless steel, a metal widely used in a variety of applications. According to the study, the fluoride anodic layers reduce the colonization of the surfaces by both bacteria and viruses, thus reducing the risk of acquiring infections from these sources.

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.

Measurement properties of the Foot Function Index (FFI) questionnaire: A systematic review.

OBJECTIVE: Large numbers of people are subject to alterations and pathologies in the foot. To quantify how these problems of foot function affect the quality of life, clinicians and researchers have developed measures such as the Foot Function Index (FFI). Our aim is to determine the methodological quality of the FFI including adaptations to other languages. DATA SOURCES: The studies considered in this review were extracted from the PubMed, Embase and CINAHL databases. The inclusion criteria were followed: (1) studies of patients with no previous foot or ankle pathology and aged over 18 years; (2) based on English-language patient-reported outcome measures that assess foot function; (3) the patient-reported outcome measures should present measurement properties based on COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria. REVIEW METHODS: The systematic review was conducted following the COSMIN criteria to establish the methodological quality of the original FFI, together with its variants and adaptations. The last search was carried out in May 2024. RESULTS: Of the 1994 studies obtained in the preliminary search, 20 were eligible for inclusion in the final analysis. These results are the validations and cross-cultural adaptations to the following languages: the original FFI has cross-cultural adaptation in 13 languages and the FFI-Revised Short Form has been adapted and validated for use in 2 languages. CONCLUSION: In terms of methodological quality, the FFI-Revised Short Form questionnaire is a valuable instrument for evaluating ankle and foot function and could usefully be expanded to be available in more languages.

Predictive factors for foot pain in the adult population.

BACKGROUND: Foot pain has been associated to factors like: fat, body mass index, age increased, female gender and the presence of pathologies. Although evidence is limited. The purpose is to determine the predictive factors for foot pain in the adult population. METHODS: From January to December 2021, 457 patients were > 18 years, gave signed informed consent to take part to this cross sectional study. All completed demographic data and various questionnaires related to pain: Foot Function Index, EuroQoL-5D and Visual Analogue Scale (foot pain). Anthropometric measurements were obtained using McPoil platform and foot posture was assessed by the Foot Posture Index (FPI). To determine whether a volume change is a predictive factor for foot pain, a parameter was established: the volumetric index for footwear (VIF). Factors linked to the presence of pain, including the considered VIF variables, were analyzed through multivariable logistic regression. RESULTS: Among the study population, 40.7% were male and 59.3% female. The mean age of 39.06 years and a body mass index of 25.58 Kg/cm2. The logistic regression model had a classification capability of 72.4%, a sensitivity of 72.3% and a specificity of 73%, in which, the predictors considered were the variables found to have a significant association with FFI-pain > 45 points,, showed that younger women, with a higher BMI, higher values of right FPI (pronation), poorer overall perceived health and with problems in walking were more likely to experience foot pain. CONCLUSION: Predictive factors for foot pain in the adult population include gender, age, Body Mass Index, FPI on the right foot, perceived health and mobility. Clinical implication, the presented measure aids physicians in assessing their patients´ foot pain likelihood.

Obstetric pulmonary embolism and long-term cardiovascular symptoms: a cross-sectional study in Western Mexico.

OBJECTIVES: Pulmonary embolism (PE) is an important cause of maternal mortality. There are several guidelines for its diagnosis and management, but there is little information regarding follow-up and frequency of long-term complications. The aim of the study was to determine the frequency of long-term cardiovascular symptoms in patients who had obstetric PE. METHODS: Cross-sectional study including patients who had PE during pregnancy or the puerperium. A telephone interview was conducted at least one year after PE, to determine the frequency of cardiovascular symptoms, general health, and COVID-19 infection, considering the study was conducted during the 2020 pandemic. RESULTS: In five years (2015-2019) there were eleven patients with PE, two died during the acute phase, and the rest (nine) were alive and able to answer our interview. Cardiovascular symptoms were common (6, 67 %), the most frequent were fatigue, edema, and mild dyspnea. Four patients (44 %) had slight limitation of physical activity and one (11 %) had PE recurrence. Of the six symptomatic patients four had obesity and one was overweight. CONCLUSIONS: There is a high frequency of long-term cardiovascular symptoms in patients who had PE during pregnancy or the puerperium. Stronger evidence is needed to design a long-term care pathway after obstetric PE.

Are local public expenditure reductions associated with increases in inequality in emergency hospitalisation? Time-series analysis of English local authorities from 2010 to 2017.

BACKGROUND: Reductions in local government funding implemented in 2010 due to austerity policies have been associated with worsening socioeconomic inequalities in mortality. Less is known about the relationship of these reductions with healthcare inequalities; therefore, we investigated whether areas with greater reductions in local government funding had greater increases in socioeconomic inequalities in emergency admissions. METHODS: We examined inequalities between English local authority districts (LADs) using a fixed-effects linear regression to estimate the association between LAD expenditure reductions, their level of deprivation using the Index of Multiple Deprivation (IMD) and average rates of (all and avoidable) emergency admissions for the years 2010-2017. We also examined changes in inequalities in emergency admissions using the Absolute Gradient Index (AGI), which is the modelled gap between the most and least deprived neighbourhoods in an area. RESULTS: LADs within the most deprived IMD quintile had larger pounds per capita expenditure reductions, higher rates of all and avoidable emergency admissions, and greater between-neighbourhood inequalities in admissions. However, expenditure reductions were only associated with increasing average rates of all and avoidable emergency admissions and inequalities between neighbourhoods in local authorities in England's three least deprived IMD quintiles. For a LAD in the least deprived IMD quintile, a yearly reduction of £100 per capita in total expenditure was associated with a yearly increase of 47 (95% CI 22 to 73) avoidable admissions, 142 (95% CI 70 to 213) all-cause emergency admissions and a yearly increase in inequalities between neighbourhoods of 48 (95% CI 14 to 81) avoidable and 140 (95% CI 60 to 220) all-cause emergency admissions. In 2017, a LAD average population was ~170 000. CONCLUSION: Austerity policies implemented in 2010 impacted less deprived local authorities, where emergency admissions and inequalities between neighbourhoods increased, while in the most deprived areas, emergency admissions were unchanged, remaining high and persistent.

Effect of Custom-Made Foot Orthotics on Multi-Segment Foot Kinematics and Kinetics in Individuals with Structural Hallux Limitus.

The first metatarsophalangeal joint (MTPJ) and the first ray are crucial in walking, particularly during propulsion. Limitation in this joint's sagittal plane motion, known as hallux limitus, can cause compensatory movements in other joints. Some studies assessed the impact of various foot orthoses designs on the foot biomechanics; however, a comprehensive understanding is lacking. This study compared the effects of two custom-made foot orthoses (CFOs) on the foot joint kinematics and kinetics in patients with structural hallux limitus (SHL). In this quasi-experimental study, 24 patients with hallux limitus were assessed in three conditions: (i) barefoot, (ii) shod with a cut-out custom foot orthosis (cut-out CFO), and (iii) shod with an anterior forefoot-stabilized element custom foot orthosis (AFSE CFO), fitted into a minimalist neoprene shoe. Multi-segment foot kinematics and kinetics were assessed during the stance phase of the gait. A decrease in ankle and midfoot inversion, as well as in ankle plantarflexion, was found in both orthotic conditions. Regarding the first MTPJ, a greater dorsiflexion was observed with the patient being barefoot compared to both of the conditions under study. From the current finding, it should be concluded that neither of the custom foot orthoses produced the predefined functional effects.

Update of Modified Version of the Foot Function Index Tool Spanish Version (FFI-Sp), in Patients with Rheumatoid Arthritis: Cross Sectional Study.

Background and Objectives: The Foot Function Index (FFI) is a widely recognized patient-reported outcome measure (PROM) for assessing foot functionality and its impact on quality of life in individuals with rheumatoid arthritis (RA). This study aimed to observe the behavior of the tool in the Spanish population with RA, optimize the tool, and check its functionality. Materials and Methods: A total of 549 RA patients, with a predominant female participation (75.6%). This study involved a comprehensive statistical analysis, leading to a refined version of the FFI for a Spanish-speaking population. Results: The original 23-item FFI was revised, resulting in a 15-item version by excluding items that caused confusion or were considered redundant. This modified version maintained the original's subscales of pain, disability, and activity limitation, but with an adjusted item distribution. The construct validity was confirmed through exploratory factor analysis, demonstrating excellent fit indices (Kaiser-Meyer-Olkin test = 0.926, Bartlett's test of sphericity = 4123.48, p < 0.001). The revised FFI demonstrated good internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (ICC = 0.89). Conclusions: This study highlights the applicability of the FFI in Spanish-speaking RA populations, offering a valid and reliable tool for clinicians and researchers. The modifications enhance the FFI's relevance for RA patients, facilitating better assessment and management of foot-related functional impairments.

Aetiology, epidemiology and treatment of musculoskeletal injuries in badminton players: a systematic review and meta-analysis.

The present study has two main goals: to conduct a systematic review of musculoskeletal injuries experienced by badminton players, and to examine the management of such injuries. Searches were conducted of the PROSPERO, PubMed, Scopus, and SPORTDiscus databases, from their inception until March 2023. The papers analysed were all based on a study population consisting of individuals aged 18 years or more, diagnosed with badminton-related injuries. The methodological quality assessments was using the Newcastle-Ottawa Scale and REVMAN. A total of 28 studies were included in the systematic review. In total, the analysis included 2435 participants. Of these athletes, 35.6% (1012) were female and 64.4% (1503) were male. By type of injury, sprains were the most commonly studied and the most prevalent, accounting for 36.06% of the sample. These were followed by muscle injuries, representing 23.86% of the total. Injuries to the joints were the least prevalent, accounting for 4.97% of the sample. Lower limb injuries accounted for 52.15% of the total. Of these, ankle injuries were the most common. Despite the generally low quality of the studies considered, the evidence suggests that musculoskeletal injuries, especially to the lower limb, most commonly affect badminton players of all levels.

Fitness-Dependent, Mild Mutagenic Activity of Sofosbuvir for Hepatitis C Virus.

The concept of a mild mutagen was coined to describe a minor mutagenic activity exhibited by some nucleoside analogues that potentiated their efficacy as antiretroviral agents. In the present study, we report the mild mutagen activity of sofosbuvir (SOF) for hepatitis C virus (HCV). Serial passages of HCV in human hepatoma cells, in the presence of SOF at a concentration well below its cytotoxic concentration 50 (CC50) led to pre-extinction populations whose mutant spectra exhibited a significant increase of C→U transitions, relative to populations passaged in the absence of SOF. This was reflected in an increase in several diversity indices that were used to characterize viral quasispecies. The mild mutagenic activity of SOF was largely absent when it was tested with isogenic HCV populations that displayed high replicative fitness. Thus, SOF can act as a mild mutagen for HCV, depending on HCV fitness. Possible mechanisms by which the SOF mutagenic activity may contribute to its antiviral efficacy are discussed.

Atypical Mutational Spectrum of SARS-CoV-2 Replicating in the Presence of Ribavirin.

We report that ribavirin exerts an inhibitory and mutagenic activity on SARS-CoV-2-infecting Vero cells, with a therapeutic index higher than 10. Deep sequencing analysis of the mutant spectrum of SARS-CoV-2 replicating in the absence or presence of ribavirin indicated an increase in the number of mutations, but not in deletions, and modification of diversity indices, expected from a mutagenic activity. Notably, the major mutation types enhanced by replication in the presence of ribavirin were A→G and U→C transitions, a pattern which is opposite to the dominance of G→A and C→U transitions previously described for most RNA viruses. Implications of the inhibitory activity of ribavirin, and the atypical mutational bias produced on SARS-CoV-2, for the search for synergistic anti-COVID-19 lethal mutagen combinations are discussed.

Thrombotic microangiopathy in patients with malignant hypertension.

BACKGROUND: Thrombotic microangiopathy (TMA) is a complication of malignant hypertension (mHTN) attributed to high blood pressure (BP). However, no studies have investigated in patients with mHTN of different aetiologies whether the presence of TMA is associated with specific causes of mHTN. METHODS: We investigated the presence of TMA (microangiopathic haemolytic anaemia and thrombocytopenia) in a large and well-characterized cohort of 199 patients with mHTN of different aetiologies [primary HTN 44%, glomerular diseases 16.6%, primary atypical haemolytic uraemic syndrome (aHUS) 13.1%, renovascular HTN 9.5%, drug-related HTN 7%, systemic diseases 5.5%, endocrine diseases 4.5%]. Outcomes of the study were kidney recovery and kidney failure. RESULTS: Patients with TMA [40 cases (20.1%)] were younger, were more likely female and had lower BP levels and worse kidney function at presentation. Their underlying diseases were primary aHUS (60%), drug-related mHTN (15%), glomerular diseases [all of them immunoglobulin A nephropathy (IgAN); 10%], systemic diseases (10%) and primary HTN (5%). The presence of TMA was 92.3% in primary aHUS, 42.9% in drug-related HTN, 36.4% in systemic diseases, 12.1% in glomerular diseases and 2.3% in primary HTN. No patient with renovascular HTN or mHTN caused by endocrine diseases developed TMA, despite BP levels as high as patients with TMA. A higher proportion of TMA patients developed kidney failure as compared with patients without TMA (56.4% versus 38.9%, respectively). CONCLUSIONS: The presence of TMA in patients with mHTN should guide the diagnosis towards primary aHUS, drug-related mHTN, some systemic diseases and IgAN, while it is exceptional in other causes of mHTN.

Recurrence of immune complex and complement-mediated membranoproliferative glomerulonephritis in kidney transplantation.

INTRODUCTION: Membranoproliferative glomerulonephritis (MPGN) represents a histologic pattern of glomerular injury that may be due to several aetiologies. Few studies have comprehensively analysed the recurrence of MPGN according to the current classification system. METHODS: We collected a multicentre, retrospective cohort of 220 kidney graft recipients with biopsy-proven native kidney disease due to MPGN between 1981 and 2021 in 11 hospitals. Demographic, clinical and histologic parameters of prognostic interest were collected. The main outcomes were time to kidney failure, time to recurrence of MPGN and disease remission after recurrence. RESULTS: The study group included 34 complement-mediated and 186 immune complex-mediated MPGN. A total of 81 patients (37%) reached kidney failure in a median follow-up of 79 months. The main predictors of this event were the development of rejection episodes and disease recurrence. In all, 54 patients (25%) had a disease recurrence in a median of 16 months after kidney transplantation. The incidence of recurrence was higher in patients with dysproteinaemia (67%) and complement-mediated MPGN (62%). In the multivariable model, complement-mediated MPGN emerged as a predictor of recurrence. A total of 33 patients reached kidney failure after recurrence. The main determinants of no remission were early time to recurrence (<15 months), estimated glomerular filtration rate <30 mL/min/1.73 m2 and serum albumin <3.5 g/dL at the time of recurrence. CONCLUSIONS: One-fourth of the patients with native kidney disease due to MPGN developed clinical recurrence in the allograft, especially in cases with complement-mediated disease or in those associated with dysproteinaemia. The kidney outcomes of disease recurrence with currently available therapies are heterogeneous and thus more effective and individualized therapies are needed.

Transplantation of organs from SARS-CoV-2-positive donors: Preliminary experience from Spain.

BACKGROUND: The utilization of non-lung organs from deceased donors with a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the time of donation can be lifesaving, although the safety of this policy must be assessed. METHODS: This is a nationwide, prospective study, reporting the experience on the utilization of non-lung organs from SARS-CoV-2-positive donors between December 15, 2020 and May 31, 2022 in Spain. RESULTS: A total of 69 patients received a solid organ transplant (41 kidney, 18 liver, 8 heart, and 2 combined liver-kidney) obtained from 32 donors with a positive SARS-CoV-2 PCR at the time of donation (four of them with a cycle threshold value <30). All recipients tested negative for SARS-CoV-2 and were free of coronavirus disease 2019 (COVID-19) symptoms prior to transplantation. Nasopharyngeal swab turned positive for SARS-CoV-2 PCR in 4 (5.8%) recipients at 3, 8, 11, and 20 days after transplantation, though evidence did not support a donor-derived COVID-19. Four kidney recipients lost their grafts and two patients died: one heart recipient due to cardiogenic shock and one combined liver-kidney recipient due to lung hypertension and right heart failure. Graft losses and patient deaths were deemed unrelated to the donor SARS-CoV-2 status by the treating teams. No other adverse reactions were reported. CONCLUSIONS: This preliminary experience supports the safety of the use of organs other than lungs from SARS-CoV-2 PCR-positive donors, in alignment with previous series. However, the impact of SARS-CoV-2 infection upon organ quality should be established in future research.

Experience with abatacept in refractory lupus nephritis.

Lupus nephritis is a major cause of morbidity in patients with systemic lupus erythematosus. Responsiveness to treatment is crucial to avoid chronic kidney disease. New molecules have been developed in recent years to improve renal survival rates. Biological therapies as coadjutant to conventional induction treatment have been tested in randomized clinical trials with heterogeneous results. Like many others biologic therapies, Abatacept has not shown a clear benefit in the context of clinical trials. We present two cases of lupus nephritis patients in whom addition of abatacept resulted in complete remission of the renal disease. The first case described a 49-year-old male with class IV lupus nephritis with nephrotic range proteinuria and high immunological activity refractory to conventional treatment with cyclophosphamide and corticosteroids and multitarget therapy with tacrolimus, mycophenolate mofetil and prednisone. Several biological therapies (rituximab, belimumab and tocilizumab) were unsuccessfully tried, so that abatacept was added to his background multitarget therapy showing complete clinical response. The second case described a 52-year-old female with class IV lupus nephritis treated initially with conventional treatment with partial response. In successive renal flares with nephrotic proteinuria, she showed intolerance to rituximab and refractoriness to voclosporin. Finally, abatacept was added to her background therapy with MMF and PDN showing complete and maintained remission of the disease. In no case the use of abatacept was associated with serious adverse events. Based on our experience, abatacept should be considered as a safe rescue therapy in patients with refractory lupus nephritis and proteinuria with nephrotic range. In addition to this case, we reviewed the use of abatacept in lupus nephritis in the literature.