IFI207, a young and fast-evolving protein, controls retroviral replication via the STING pathway.

Mammalian AIM-2-like receptor (ALR) proteins bind nucleic acids and initiate production of type I interferons or inflammasome assembly, thereby contributing to host innate immunity. In mice, the Alr locus is highly polymorphic at the sequence and copy number level, and we show here that it is one of the most dynamic regions of the genome. One rapidly evolving gene within this region, Ifi207, was introduced to the Mus genome by gene conversion or an unequal recombination event a few million years ago. Ifi207 has a large, distinctive repeat region that differs in sequence and length among Mus species and even closely related inbred Mus musculus strains. We show that IFI207 controls murine leukemia virus (MLV) infection in vivo and that it plays a role in the STING-mediated response to cGAMP, dsDNA, DMXXA, and MLV. IFI207 binds to STING, and inclusion of its repeat region appears to stabilize STING protein. The Alr locus and Ifi207 provide a clear example of the evolutionary innovation of gene function, possibly as a result of host-pathogen co-evolution.IMPORTANCEThe Red Queen hypothesis predicts that the arms race between pathogens and the host may accelerate evolution of both sides, and therefore causes higher diversity in virulence factors and immune-related proteins, respectively . The Alr gene family in mice has undergone rapid evolution in the last few million years and includes the creation of two novel members, MndaL and Ifi207. Ifi207, in particular, became highly divergent, with significant genetic changes between highly related inbred mice. IFI207 protein acts in the STING pathway and contributes to anti-retroviral resistance via a novel mechanism. The data show that under the pressure of host-pathogen coevolution in a dynamic locus, gene conversion and recombination between gene family members creates new genes with novel and essential functions that play diverse roles in biological processes.

Recurrence of Drug-Induced Lupus Secondary to Vedolizumab Use in a Patient With Crohn's Disease.

Drug-induced lupus is an autoimmune phenomenon characterized by the development of systemic lupus erythematosus-like clinical features after drug exposure. The entity is a clinical diagnosis. Evaluation consists of recognizing systemic lupus erythematosus-like features, identifying an appropriate causative agent, observing elevations of characteristic autoantibodies, and obtaining positive response with drug discontinuation. Vedolizumab is an anti-α4ß7 antibody used in the treatment of ulcerative colitis and Crohn's disease. We report a novel case of drug-induced lupus recurrence secondary to vedolizumab use in a patient with Crohn's disease, emphasizing diagnostic evaluation, and provide a brief review of the published literature.

Sedación paliativa: percepción del personal médico e implicaciones en la práctica clínica en un hospital de alta complejidad / Medical staff perception of palliative sedation and its implications for clinical practice in a high complexity hospital

Introducción: el cuidado paliativo tiene como objetivo controlar los síntomas y la ganancia en calidad de vida de los pacientes con enfermedades progresivas, avanzadas o con pobre opción curativa. Juega un papel fundamental en los síntomas refractarios y la falta de educación sobre esta materia en todos los niveles de la formación médica lleva a generar que no sea considerada, se tenga un concepto equivocado o exista temor en su aplicación. Materiales y métodos: estudio descriptivo de corte trasversal para definir el conocimiento, las percepción personal y profesional sobre la sedación paliativa, mediante la aplicación en una encuesta a 201 participantes entre estudiantes de medicina de último año, médicos generales, residentes y especialistas de diferentes especialidades en un hospital universitario de alta complejidad en Cali, Colombia en 2021. Resultados: 57,2% eran hombres, 3,98% desempeñaba la mayoría de su actividad en salas de cirugía, 25,4% en consulta externa, 57,2% en hospitalización y 13,4% en urgencias. En cuanto a la formación en cuidados paliativos 19,9% consideró que fue ninguna, 67,7% poca y 12,4% mucha, 16,4% desconocía la definición de enfermedad terminal y 25,4% la de sedación paliativa. El 90% no pudo diferenciar los objetivos de la sedación paliativa y la eutanasia, aunque 94,5% reconoció que era importante controlar el sufrimiento de los pacientes y que la sedación era una opción terapéutica. Discusión y conclusiones: la sedación paliativa es una intervención importante en los pacientes con síntomas refractarios, existen brechas de conocimiento que limitan su aplicación clínica, lo que debe fortalecer la educación en este aspecto en todos los niveles de la formación médica.

Introduction: palliative care is geared to symptoms control and quality of life improvement among patients with advanced, progressive, or non-curative diseases. It plays a fundamental role on refractory symptoms and lack of teaching on this matter, at all medical training levels, leads to unawareness and misunderstanding or fear to administer it. Materials and methods: a descriptive, cross-sectional study conducted to define knowledge, and personal and professional perception of palliative sedation (PS), using a survey applied to 201 participants selected from last year medical students, general practitioners, residents, and different specialists at a high complexity university hospital in Cali, Colombia in 2021. Results: 57.2% were men, 3.98% worked mostly in operating rooms, 25.4% in the outpatient clinic, 57.2% in the hospitalization ward and 13.4% in the emergency room. Regarding training in palliative care 19.9% considered they had not received any training, 67.7% little and 12.4% a lot, 16.4% did not know the definition of terminal illness and 25.4% did not know the definition of PS. 90% would not distinguish between the purpose of palliative sedation and euthanasia, although 94.5% recognized that preventing patient suffering was important and that sedation was a therapeutic option. Discussion and conclusions: palliative sedation is an important intervention in patients with refractory symptoms. Knowledge gaps limiting its clinical administration show the need of strengthening education on PS, at all levels of medical training.

Clinical Presentation of Schnitzler's Syndrome: A Rare Autoimmune Disease.

Schnitzler's Syndrome (SS) is a rare late-onset acquired autoinflammatory disorder which consists of chronic urticaria associated with a monoclonal IgM-kappa gammopathy, arthralgias, skeletal hyperostosis, lymphadenopathy, and recurrent constitutional symptoms. The average age of diagnosis is 51 years with a slight male predominance with a male to female ratio of 1.6. Diagnosis of SS requires the presence of 2 major criteria including chronic urticaria and monoclonal IgM along with at least two of the following minor criteria: recurrent intermittent fevers, bone pain, arthralgias, elevated erythrocyte sedimentation rate (ESR), neutrophilic dermal infiltrate on skin biopsy, and leukocytosis or elevated C-reactive protein (CRP). Early diagnosis and clinical awareness are paramount in SS as it is associated with a 15-20% risk of lymphoproliferative malignancy. The median overall survival is 12.8 years. We present a case of a 39-year-old female with new onset urticaria associated with recurrent fevers and joint pain. Symptoms were refractory to steroids, and high dose antihistamines. Multi-disciplinary evaluation resulted in the ultimate diagnosis of Schnitzler's Syndrome. The patient was ultimately treated with canakinumab (Il-1 inhibitor), with near resolution of symptoms. This case demonstrates the importance of a broad differential diagnosis and maintaining a high clinical suspicion for rare diseases when presented with a complex form of an otherwise common condition.

Orthodontic treatment need, the types of brackets and the oral health-related quality of life.

BACKGROUND: Malocclusion can affect the oral health-related quality of life (OHRQoL). The influence of the orthodontic treatment need (OTN) and the type of brackets on OHRQOL is not clear. OBJECTIVES: The aim of the present study was to determine the relationships between OTN and the bracket type and OHRQoL during the first 6 months of orthodontic treatment (OT) in adult patients. MATERIAL AND METHODS: This cohort study was conducted at the Department of Orthodontics of a private university. A total of 216 patients aged ≥18 years participated in the study (106 patients with conventional brackets and 110 with self-ligating brackets). The OHRQoL was evaluated using the 14-item Oral Health Impact Profile (OHIP-14) at 5 time points - before OT (T0), and at 24/48 h (T1), 1 month (T2), 3 months (T3), and 6 months (T4) after the installation of the orthodontic appliance. The OTN was evaluated with the dental aesthetic index (DAI) by 2 previously calibrated operators. For the statistical analysis, the χ2 test and the Mann-Whitney U test were used. Additionally, Poisson regression models were performed. RESULTS: The evidence of an association between OHRQoL and OTN was found only at T3 (p = 0.0095). No association was found between OHRQoL and the bracket type. However, in the regression models, OHRQoL was statistically significantly worse at T3 in the group with a greater OTN (IRR (incidence rate ratio) = 1.34; 95% CI (confidence interval): 1.21;1.48) and at T4 in the self-ligation group (IRR = 1.23; 95% CI: 1.12;1.36). CONCLUSIONS: The OHRQoL was affected in the same way at the beginning of OT, regardless of OTN and the bracket type used. However, a worse OHRQoL was observed at 3 months in subjects with greater OTN and at 6 months in patients with self-ligating brackets.

Measuring treatment outcomes and change in disease activity in giant cell arteritis: a systematic literature review informing the development of the EULAR-ACR response criteria on behalf of the EULAR-ACR response criteria in giant cell arteritis task force.

OBJECTIVES: To identify criteria and descriptors used to measure response to treatment and change in disease activity in giant cell arteritis (GCA). METHODS: A systematic literature review (SLR) to retrieve randomised controlled trials (RCTs) and longitudinal observational studies (LOS). Criteria and descriptors of active disease, remission, response, improvement, worsening and relapse were extracted. RCTs, LOS with >20 subjects, and qualitative research studies were included. RESULTS: 10 593 studies were retrieved, of which 116 were included (11 RCTs, 104 LOS, 1 qualitative study). No unified definition of response to therapy was found. Most RCTs used composite endpoints to assess treatment outcomes. Active disease was described in all RCTs and 19% of LOS; and was largely defined by a combination of clinical and laboratory components. Remission was reported in 73% of RCTs and 42% of LOS; It was predominantly defined as the combination of clinical and laboratory components. One LOS reported response with a definition resembling the definition of remission from other studies. Improvement was rarely used as an endpoint and it was mostly a surrogate of remission. No study specifically defined worsening. Relapse was reported in all RCTs and 86% of LOS. It was predominantly defined as the combination of clinical, laboratory and treatment components. CONCLUSIONS: The results of this SLR demonstrate that definitions of response used in clinical studies of GCA are scant and heterogeneous. RCTs and LOS mainly used remission and relapse as treatment outcomes. The descriptors identified will inform the development of the future European Alliance of Associations for Rheumatology-American College of Rheumatology response criteria for GCA.

Urticaria after breakthrough Omicron BA.5.1 severe acute respiratory syndrome coronavirus 2 infection in a triple-vaccinated (Pfizer) patient: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 continues to threaten public health. The virus is causing breakthrough infections in vaccinated individuals. Also, scarce information is available about cutaneous manifestations after severe acute respiratory syndrome coronavirus 2 infection. CASE PRESENTATION AND FINDINGS: A case of a triple-vaccinated (Pfizer) 37-year-old Hispanic American (Colombian) male who developed urticaria after Omicron BA.5.1 severe acute respiratory syndrome coronavirus 2 breakthrough infection is described. Virus isolation and whole genome sequencing along with immune and molecular assays were performed. Dermatological manifestations (skin rash and urticaria) after Omicron BA.5.1 infection were observed. Sequence analysis of the Omicron BA.5.1 isolate also revealed several important mutations. Hemogram analysis revealed leukocytosis and neutrophilia. Serology testing revealed anti-spike immunoglobulin G serum titers but negative detection of immunoglobulin M at 10 days after symptom onset. Anti-nucleocapsid, anti-spike 1 immunoglobulin G, anti-spike trimer, and anti-receptor-binding-domain immunoglobulin G and immunoglobulin E sera were detected at different titers 10 days after symptom onset. Several serum levels of chemokines/cytokines (Interferon-α, interferon-γ, interleukin-12/interleukin-23p40, interleukin-18, interferon gamma-induced protein-10, monocyte chemoattractant protein-1, monokine induced by gamma, macrophage inflammatory protein-1α, chemokine (C-C motif) ligand-5 , tumor necrosis factor-ß1, Tumor necrosis factor-α) were detected, but interleukin-2, interleukin-4, interleukin-6, interleukin-8, and interleukin-17A were below the limit of detection. INTERPRETATION AND CONCLUSIONS: To our knowledge, this is the first study describing skin effects of a severe acute respiratory syndrome coronavirus 2 Omicron BA.5 variant breakthrough infection in a triple-vaccinated patient in Colombia. Several important mutations were found in the spike glycoprotein of the virus isolated; these mutations are associated with immune evasion and changes in antigenic properties of the virus. Physicians overseeing coronavirus disease 2019 cases should be aware of the potential skin effects of the infection. Pathogenesis of severe acute respiratory syndrome coronavirus 2 infection and its association with proinflammatory cytokines and chemokines may enhance the development of urticaria and other skin manifestations in immunized individuals. However, further studies are needed to better understand the complexity of coronavirus disease in such situations.

Lower tear meniscus height measured by optical coherence tomography in children.

INTRODUCTION: While optical coherence tomography (OCT) measurements of the lower tear meniscus height (LTMH) have been reported in adults, here we obtained LTMH measurements through Fourier Domain OCT in healthy children and compared these with values obtained in healthy adults. METHODS: Participants were children 7-17 years of age and a control group of adults 20-40 years of age. Inclusion criteria were no abnormal eye conditions or the use of contact lenses. Candidates who fulfilled the TFOS DEWS II criteria for dry eye disease (DED) were excluded. All subjects underwent LTMH measurement (OCT Spectralis) and tests for non-invasive tear break-up time and ocular surface staining. Participants also completed the ocular surface disease index questionnaire. RESULTS: A total of 86 children and 27 adults were included. Mean LTMH values in the children and adult groups were 217.40 ± 71.40 µm and 225.0 ± 54.86 µm, respectively; p = 0.53. However, 59.3% of the children had an LTMH ≤210 µm suggestive of DED, compared with only 33.3% of adults (p = 0.02). For the children, no significant differences in LTMH were observed with sex or for those more or less than 12 years of age. CONCLUSIONS: Optical coherence tomography-derived LTMH measurements were obtained in healthy children. While values were similar in children and adults, a greater proportion of children had an LTMH compatible with a diagnosis of DED. More studies in different paediatric populations are required to establish a complete set of normative LTMH measurements.

What is a response in randomised controlled trials in giant cell arteritis?

Glucocorticoids (GCs) are the gold standard for treatment of giant cell arteritis (GCA); however, there is a need for studies on GC-sparing agents, given that up to 85% of patients receiving GC only develop adverse events. Previous randomised controlled trials (RCTs) have applied different primary endpoints, limiting the comparison of treatment effects in meta-analyses and creating an undesired heterogeneity of outcomes. The harmonisation of response assessment is therefore an important unmet need in GCA research. In this viewpoint article, we discuss the challenges and opportunities with the development of new, internationally accepted response criteria. A change of disease activity is a fundamental component of response; however, it is debatable whether the ability to taper GC and/or the maintenance of a disease state for a specific time period, as applied in recent RCTs, should be part of response assessment. The role of imaging and novel laboratory biomarkers as possible objective markers of disease activity needs further investigation but might be a possibility when drugs directly or indirectly influence the levels of traditional acute-phase reactants such as erythrocyte sedimentation rate and C reactive protein. Futures response criteria might be constructed as a multidomain set, but the questions about which domains will be included and what their relative weights will be still need to be answered.

Prevalence of convergence insufficiency among Spanish school children aged 6 to 14 years

Clinical relevanceConvergence insufficiency (CI) at an early age can lead to learning difficulties affecting school performance. The aim of this study was to examine the prevalence of CI in a non-clinical population of Spanish children using well defined clinical criteria and to determine whether sex is a risk factor.MethodsVisual acuity and binocular vision tests were performed in 628 children aged 6–14 years (mean age 9.6 ± 1.3 years) at three schools in the Madrid Community, Spain. To assess CI prevalence we used CITT (Convergence Insufficiency Treatment Trial) criteria. The three signs considered were: i) exophoria at least 4∆ greater at near than at far; ii) near break point of convergence (NPC) ≥ 6 cm; and iii) reduced positive fusional vergence (PFV) at near (≤ 15∆ base-out break or failed Sheard's criterion).ResultsThe CI prevalence detected was 5.30% (33 children). Proportions of children with one or two signs of CI were 23.76% (148 children) and 12.20% (76 children), respectively. No differences in these CI rates by sex were detected.ConclusionThe clinically significant CI prevalence observed here suggests the need for more binocular vision screening programmes in school settings. (AU)

Measures of accommodative function in secondary school year 9 and year 13: a 4-year longitudinal study.

PURPOSE: To characterize accommodative function in secondary school children in year 9 and year 13 and assess the possible relationship between daily working conditions (number of near work hours and distances) and accommodation variables related to accommodative excess. METHODS: This was a prospective study. Participants were 43 subjects who were first examined in year 9 and then again when they were in year 13. The accommodation variables measured in each session were as follows: accommodation amplitude (AA), accommodative response (AR), monocular and binocular accommodation flexibility (MAF and BAF), negative relative accommodation (NRA), and positive relative accommodation (PRA). Other data recorded were the number of hours spent working at near vision tasks and the distances used for these tasks. Participants were classified as those with accommodation variables within the normal range (NA) and those with variables suggesting accommodative excess (AE). RESULTS: Several accommodative function variables were below normative values in both year 9 and year 13. The number of subjects classified as having AE went from 27.9% in year 9 to 58.1% in year 13 according to AR (p < 0.005) and from 23.3 to 46.5% according to MAF (p = 0.024). More near work was reported in year 13 (44.6 h/week) than year 9 (32.7 h/week) (p < 0.001). It emerged that subjects in year 13 spent more hours working at near if they had AE than if they were assigned to the NA group. No differences were detected in near work distances used by subjects in the NA and AE groups in both years. CONCLUSIONS: In both school years, values outside the norm were detected in several accommodative function measures. Also, devoting more hours to near work was linked to a greater extent of accommodative excess. We would therefore recommend regular accommodative function assessment in secondary school children.

Paving the Way: Contributions of Big Data to Apicomplexan and Kinetoplastid Research.

In the age of big data an important question is how to ensure we make the most out of the resources we generate. In this review, we discuss the major methods used in Apicomplexan and Kinetoplastid research to produce big datasets and advance our understanding of Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma and Leishmania biology. We debate the benefits and limitations of the current technologies, and propose future advancements that may be key to improving our use of these techniques. Finally, we consider the difficulties the field faces when trying to make the most of the abundance of data that has already been, and will continue to be, generated.

Identificación y secuenciación de SARS-CoV-2 en una leona africana (Panthera leo), bajo el cuidado técnico profesional, en Colombia

Objetivo Identificar y caracterizar el virus SARS-CoV-2 en una leona africana (Panthera leo), hembra, de edad avanzada, que presentó por varios meses signos relacionados con enfermedad respiratoria atípica. Métodos Se tomaron muestras de hisopados nasales 23 días después de haber reportado secreción nasal inicial. Se realizó la detección del virus SARS-Cov2 mediante RT-qPCR y posteriormente se caracterizó el genoma completo mediante secuencia Illumina. Resultados Desde el punto de vista clínico, los resultados encontrados en las muestras de sangre no mostraron cambios evidentes que se pudieran relacionar con el virus o con todos los signos descritos desde el inicio del caso. Para la secuenciación genómica los análisis mostraron una alineación múltiple comparativa entre los tres genomas (muestra Leona, FIP u NC_045512 [Wu han]) por medio de Mauve, centrado en los genes Spike, E y M (archivo complementario, parte B). Se logró identificar 5 segmentos muy similares entre Leona y NC_045512 (Wuhan). Conclusiones Es necesario adelantar más investigaciones para estandarizar el diagnóstico de esta patología en los animales. Así mismo, se requieren estudios genómicos en estas especies. Además, se evidenció con la revisión del estado de la cuestión que existen muchos vacíos del conocimiento en la implicación zoonótica de la pandemia y en el conocimiento de este virus en animales domésticos y silvestres, lo que supone un reto importante para las investigaciones de aquí en adelante.

Objective To identify and characterize the SARS-CoV-2 virus in an elderly African lioness (Panthera leo) that presented signs related to atypical respiratory disease for several months. Methods Nasal swab samples were taken 23 days after infection. have reported initial nasal discharge. Results The SARS-Cov2 virus was detected by RT-qPCR and the complete genome was subsequently characterized by Illumina sequencing. The results found in the blood samples did not show obvious changes that could be related to the virus or to the signs described from the beginning of the case. For genomic sequencing the analyzes showed a comparative multiple alignment between the three genomes (sample Leona, FIP or NC_045512 (Wu han)) by means of Mauve, focusing on the Spike, E and M genes (Supplementary file, part B); 5 very similar segments between Leona and NC_045512 (Wuhan) was identified. Conclusions It is necessary to carry out more research to standardize the diagnosis of this pathology in animals and guarantee access to it. Also, genomic studies in these species. Additionally, it was evidenced with the literature review that there are many knowledge gaps in the zoonotic implication of the Pandemic and in the knowledge of this virus in domestic and wild animals, which represents an important challenge for research from now on.

Tratamiento estético de defecto de esmalte utilizando tratamiento combinado con resina infiltrante: Reporte de caso / Aesthetic treatment of enamel defect using combined therapy with resin infiltration: Case report

RESUMEN: La presencia de defectos en el esmalte puede afectar negativamente la autoestima de pacientes jóvenes, haciendo muchas veces necesario realizar un tratamiento estético. El tratamiento con resinas infiltrantes, permite obtener resultados estéticos sin realizar remoción del tejido dentario. Sin embargo, en casos de defectos de esmalte con fracturas post-eruptivas, la resina infiltrante por sí sola, no permite obtener un resultado óptimo. El presente reporte utiliza la combinación de resina infiltrante con resina compuesta directa para obtener resultados estéticos. De esta manera, al infiltrar primero, se mejora el aspecto estético de la lesión y también las características adhesivas del esmalte defectuoso, para posteriormente restaurar el contorno perdido aplicando una delgada capa de resina compuesta de translucidez media.

ABSTRACT: The presence of enamel defects can affect negatively the self-esteem of young patients, making it necessary to carry out an aesthetic treatment. Resin infiltration treatment provides aesthetic results without the necessity of removing the defective dental tissue. However, in cases of enamel defects with post-eruptive fractures, the treatment with resin infiltration by itself does not achieve optimal results. This report uses the combination of resin infiltration with direct resin composite to obtain an aesthetic result. This way, by first infiltrating, the aesthetic appearance of the lesion is improved, as well as the adhesive characteristics of the enamel, and subsequently the contour is restored by applying a thin layer of medium translucency resin composite.

Hemolysis in Hemodialysis, Secondary to Severe Vena Cava Stenosis.

Complications in hemodialysis patients are increasingly rare thanks to advances in technology, including more compatible membranes, more flexible lines, safety in water treatments, alarms in the circuit, and standardization in dialysate fluids plus exhaustive chemical and microbiological tests. In addition, it is highly unusual having hemolysis on hemodialysis; however, it is a life-threatening complication, so the cause must be identified and early managed. The etiology can be chemical or mechanical; however, so far, there are no reports in the literature of an association with severe stenosis of the vena cava, as it is described in the case reported here, where a patient presented hemolysis in two hemodialysis sessions, without initially being possible to find the cause; the only identifiable factor was that he had a dysfunctional tunneled jugular catheter, with a history of difficult vascular access. The patient underwent interventional radiology, finding 99% stenosis of the vena cava, which prevented the passage of the contrast agent to the atrium. Angioplasty and catheter replacement were performed, with a resolution of the complication; the subsequent dialysis therapies were satisfactory.

Type II cryoglobulinemic vasculitis in the setting of MALT lymphoma.

The objectives of this article are to present a case of type II cryoglobulinemic vasculitis, explain why mucosa-associated lymphoid tissue (MALT) lymphoma is an unusual cause of type II cryoglobulins and to discuss the aetiology, epidemiology, pathophysiology and treatment of cryoglobulinemic vasculitis. A 67-year-old woman presented with 4 months of weight loss, intermittent epistaxis and a purpuric skin rash. Prior to presentation, she was found to have an elevated rheumatoid factor. Further investigation revealed an acute kidney injury and elevated type II cryoglobulins suspicious for cryoglobulinemic vasculitis, which was confirmed by kidney biopsy. Additional workup for the weight loss included biopsy of newly found splenomegaly. Pathology revealed MALT lymphoma, a rare cause of type II cryoglobulinemic vasculitis. Successful medical therapy required treating the underlying malignancy with rituximab and high-dose steroids. After initial resolution of symptoms with this regimen, the patient's vasculitis worsened, which was thought to be secondary to undertreatment of the lymphoma. Bendamustine was added to further treat the lymphoma, after which the patient recovered and was able to discharge without recurrence of symptoms at 6 months.

Mesangial expansion at 5 years predicts death and death-censored graft loss after renal transplantation.

Death with a functioning graft and death-censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5-year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m2 ) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5-year biopsies, moderate-to-severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1-year post-transplant. Moderate-to-severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death-censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow-up post-transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.

Antirheumatic Disease Therapies for the Treatment of COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVE: Antirheumatic disease therapies have been used to treat coronavirus disease 2019 (COVID-19) and its complications. We conducted a systematic review and meta-analysis to describe the current evidence. METHODS: A search of published and preprint databases in all languages was performed. Included studies described ≥1 relevant clinical outcome for ≥5 patients who were infected with severe acute respiratory syndrome coronavirus 2 and were treated with antirheumatic disease therapy between January 1, 2019 and May 29, 2020. Pairs of reviewers screened articles, extracted data, and assessed risk of bias. A meta-analysis of effect sizes using random-effects models was performed when possible. RESULTS: The search identified 3,935 articles, of which 45 were included (4 randomized controlled trials, 29 cohort studies, and 12 case series). All studies evaluated hospitalized patients, and 29 of the 45 studies had been published in a peer-reviewed journal. In a meta-analysis of 3 cohort studies with a low risk of bias, hydroxychloroquine use was not significantly associated with mortality (pooled hazard ratio [HR] 1.41 [95% confidence interval (95% CI) 0.83, 2.42]). In a meta-analysis of 2 cohort studies with some concerns/higher risk of bias, anakinra use was associated with lower mortality (pooled HR 0.25 [95% CI 0.12, 0.52]). Evidence was inconclusive with regard to other antirheumatic disease therapies, and the majority of other studies had a high risk of bias. CONCLUSION: In this systematic review and meta-analysis, hydroxychloroquine use was not associated with benefit or harm regarding COVID-19 mortality. The evidence supporting the effect of other antirheumatic disease therapies in COVID-19 is currently inconclusive.