Retrospective study of the incidence of sarcoidosis-like reaction in patients treated with immunotherapy.

AIM: To assess the frequency of radiographically evident drug-induced sarcoidosis-like reaction (DISR) in patients treated with anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) therapy, anti-programmed cell death protein 1 (PD-1) therapy, or a combination of both in a single centre. MATERIALS AND METHODS: The images and medical records of 457 patients with metastatic melanoma or head and neck cancer treated with either anti-CTLA-4 therapy, anti-PD-1 therapy, or a combination of both at University of California medical centre were reviewed retrospectively and the incidence of radiological manifestations of DISR was assessed among these treatment groups. RESULTS: Radiological manifestations of DISR were found in 19/457 patients (4.1%). The mean interval from the initiation of immunotherapy to development of DISR was 5.5 months (range 2.3-13.5 months). Mean interval from radiological detection of DISR to imaging evidence of resolution was 5.8 months (range 1.6-18.3 months). Three patients out of 81 (3.7%), 11/297 (3.7%), and 5/79 (6.3%) developed sarcoidosis-like reaction after treatment with anti-CTLA-4 antibody, anti-PD-1 antibody, and a combination of both, respectively. Most patients with DISR were asymptomatic and did not require systemic therapy. Most patients did not demonstrate concomitant increased maximum standardised uptake value (SUVmax) in other organs on their integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT). CONCLUSIONS: In the present retrospective study of patients treated with immune checkpoint inhibitors (ICIs), DISR occurred in approximately 3.7% of patients treated with either anti-CTLA-4 or anti-PD-1 antibody and 6.3% of patients treated with a combination of both.

A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19).

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.

Influence of operational conditions and wastewater properties on the removal of organic micropollutants through ozonation.

The objective of this study was to evaluate the influence of operational conditions and wastewater properties on the removal of pharmaceuticals, contrast media and antibiotics through ozonation, in order to facilitate the optimization of treatment and its implementation on a full scale. Pilot-scale ozone oxidation trials were performed on treated wastewater, before and after post-precipitation, over a seven-month period, including summer and winter months. Hydraulic retention times as short as 7 min were found to be sufficient for organic micropollutant removal. A short hydraulic retention time reduces both investment costs and land use. Neither the choice of ozone dispersion method, a static mixer or a Venturi injector, nor the wastewater temperature had any significant effect on the removal efficiency of organic micropollutants, however, higher removal was achieved after on-site post-precipitation with aluminum chloride.

Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in PD-1 inhibitor-associated colitis and its mimics.

AIMS: Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of advanced malignancies by boosting immune-mediated destruction of neoplastic cells, but are associated with side effects stemming from generalised immune system activation against normal tissues. Checkpoint ligand expression in non-tumoral cells of tissues affected by immune-related adverse effects has been described in ICI-associated hypophysitis, myocarditis, and acute interstitial nephritis. We aimed to investigate the tissue expression of the immune checkpoint receptor programmed cell death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), in PD-1 inhibitor-associated colitis (PD1i colitis). METHODS AND RESULTS: PD-1 and PD-L1 immunohistochemical expression levels were analysed in 15 cases of PD1i colitis and potential mimics-infectious colitis and inflammatory bowel disease (IBD). Increased epithelial expression of PD-L1 was observed in PD1i colitis as compared with normal colon and infectious colitis, but the expression level was lower than that in IBD. Conversely, PD-1 expression in inflammatory cells was higher in infectious colitis, intermediate in IBD, and minimal or absent in normal colon and in patients receiving PD-1 inhibitors. CONCLUSIONS: Although our results do not justify the use of PD-L1 as a discriminatory marker of PD1i colitis against other entities within the differential diagnosis, they support the concept that PD1i colitis and IBD have similar pathogenetic mechanisms. They also highlight the fact that PD-L1 epithelial overexpression is a commonly used mechanism of the gastrointestinal tract mucosa to protect itself from inflammatory-mediated damage resulting from different aetiologies, which probably underpins the high incidence of gastrointestinal immune-related adverse effects in patients receiving ICI therapies, in whom this mechanism is disrupted.

Analysis of the effectiveness of training school personnel in the management of food allergy and anaphylaxis.

BACKGROUND: Food allergy is a very frequent and increasingly common disease in children and adolescents. It affects quality of life and can even be life-threatening. Given that 10-18% of allergic/anaphylactic food reactions take place in schools, it is essential to provide school personnel with training on the management of reactions. METHODS: The Allergy Unit of Hospital Universitario de Fuenlabrada, Spain, organized a conference entitled "Management of Food Allergy in Children and Adolescents in School Centers" during which teachers, cooks, cafeteria monitors, and summer-camp leaders underwent a training course. Attendees filled out a questionnaire with eight questions before and after the course to assess their self-efficacy in management of food allergy and anaphylaxis. The results were compared. RESULTS: A total of 191 people participated (51% dining-room monitors, 24% teachers, 13% cooks, and 12% other professions). The areas in which the attendees presented the lowest confidence before receiving the course were recognition of symptoms and treatment of the reactions/anaphylaxis. The mean score for each of the eight concepts evaluated improved after the training course. This improvement was significant in the management of anaphylaxis. CONCLUSIONS: Our study demonstrates the usefulness of a self-efficacy scale in school personnel as a tool to assess the ability to manage food allergy and anaphylaxis. It can help to identify problem areas in which more specific training programs can be implemented.

Effectiveness and safety of two 18-gauge needle types on native and allograft renal biopsies.

Percutaneous biopsy is a key diagnostic tool for both native and allograft kidney diseases. Adequacy criteria vary, but at a minimum, a biopsy should allow the pathologist to reach a diagnosis and provide prognostic information such as the degree of interstitial fibrosis and tubular atrophy (IF/TA) and percentage of glomerulosclerosis. Whereas most studies use glomerular counts as a surrogate for biopsy adequacy, the amount and preservation of tubulointerstitium is equally important, considering IF/TA is a major prognostic parameter for most medical renal diseases. Many studies have compared the diagnostic adequacy of different gauge needles; however few have investigated performance differences between same gauge needles. In this study, we retrospectively analyzed 235 renal biopsies performed at a single center in Canada over 2years to compare the utilization, safety, diagnostic and prognostic performance of two 18-gauge needles in native and allograft kidney biopsies. We found no significant difference in needle utilization between native and allograft kidneys, or between trainees and staff radiologists. The total tissue yielded area, glomerular counts, percentage of inadequate biopsies and number of passes were similar; however the number of cases in which IF/TA evaluation was deemed not possible was higher for biopsies using disposable instrument needles (4.3% vs. 0%; p=0.01). These also showed greater number of tissue fragments (median 4 for reusable vs 3 for disposable; p=0.04). We postulate that the increased tissue fragmentation might have impaired the pathologists ability to accurately assess interstitial fibrosis and tubular atrophy in biopsies obtained with the disposable instrument needles.

Interventions and decision-making at the end of life: the effect of establishing the terminal illness situation.

BACKGROUND: Many 'routine' interventions performed in hospital rooms have repercussions for the comfort of the patient, and the decision to perform them should depend on whether the patient is identified as in a terminal phase. The aim of this study is to analyse the health interventions performed and decisions made in the last days of life in patients with advanced oncological and non-oncological illness to ascertain whether identifying the patient's terminal illness situation has any effect on these decisions. METHODS: Retrospective study of the clinical histories of deceased patients in four hospitals in Granada (Spain) in 2010. Clinical histories corresponding to the last three months of the patient's life were reviewed. RESULTS: A total of 202 clinical histories were reviewed, 60 % of which were those of non-oncology patients. Opioid prescriptions (58.4 %), palliative sedation (35.1 %) and Do Not Resuscitate (DNR) orders (34.7 %) were the decisions most often reflected in the histories, and differences in these decisions were found between patients registered as terminal and those who were not registered as terminal. The most frequent interventions in the final 14 days and 48 h were parenteral hydration (96-83 %), peripheral venous catheter (90.1-82 %) and oxygen therapy (81.2-70.5 %). There were statistically significant differences between the patients who were registered as terminal and those not registered as terminal in the number of interventions applied in the final 14 days and 48 h (p = 0.01-p = 0.00) and in many of the described treatments. CONCLUSION: The recognition of a patient's terminal status in the clinical history conditions the decisions that are made and is generally associated with a lower number of interventions.

Differential expression of serine protease inhibitors 1 and 2 in Crassostrea corteziensis and C. virginica infected with Perkinsus marinus.

Proliferation of Perkinsus marinus (Dermo) in vitro is inhibited by the action of 2 serine protease inhibitors belonging to the I-84 family. We compared the levels of expression of serine protease inhibitors 1 and 2 (SPI-1 and SPI-2) in 2 oyster species (Crassostrea virginica and C. corteziensis) inoculated with the parasite P. marinus. C. virginica is well known to be susceptible to this parasite, whereas C. corteziensis is apparently more tolerant. Oysters were inoculated with trophozoites (1 × 106 trophozoites oyster-1) of P. marinus while control oysters were injected with saline solution. Oysters were maintained in a closed water system for 2 wk. The oysters were then sacrificed and parasite burden, histological damage, and gene expression were evaluated. The results showed that the challenged oysters presented a significant increase in parasite burden, which generated histological damage in digestive gland and gills. Quantitative PCR detected significant differences in SPI-1 and SPI-2 expression levels in the 2 oyster species, with C. corteziensis showing higher expression levels than C. virginica as a response to P. marinus inoculation. Our results provide valuable information for the understanding of the defense response in C. corteziensis and a possible explanation for its tolerance to the parasite.

[Outcome of posterior anorectal myectomy for the treatment of idiopathic chronic constipation]. / Resultados de la miectomía anorrectal posterior en el tratamiento del estreñimiento crónico idiopático.

OBJECIVES: The aim of this study is to assess the outcome of surgery (Lynn's myectomy) in patients with chronic persistent constipation and failure of medical treatment. MATERIAL AND METHODS: Descriptive study of patients with severe chronic constipation treated by posterior anorectal myectomy (Lynn's technique). We report data from the last 15 years, with a minimum postoperative follow-up of one year. Patients included in the study suffered from a long-term constipation refractory to medical management. Data regarding contrast enema, anorectal manometry and rectal biopsy were recorded. The procedure's outcome is classified following clinical criteria: Asymptomatic: >3 bowel movements per week, with no soiling/incontinence and with no medical treatment; Improvement: >3 bowel movements per week, with no soiling/incontinence but using laxatives occasionally. RESULTS: Nineteen myectomies were performed (median age of 8.47 years). Median time of constipation before surgery was 7.89 years. Rectal biopsy findings: 10 with ganglion cells, 4 without ganglion cells and other abnormalities in 5. Anorectal manometry was performed in 6 patients, 4 presented rectoanal inhibitory reflex. Four patients were diagnosed of Hirschsprung's disease (1 was asymptomatic after myectomy, 2 needed further surgery and 1 was lost in follow-up). Of the remaining 15 patients, 8 were asymptomatic (53.3%), 4 experienced improvement (26.6%) and 1 without clinical changes is on pelvic floor physiotherapy. Two were lost in follow-up. There were no other postoperative complications after long term follow-up. CONCLUSIONS: Lynn's myectomy is an effective and safe procedure in patients suffering from persistent chronic constipation despite of medical treatment. It is also the definitive treatment for patients with ultrashort-segment Hirschsprung's disease.

OBJETIVO: Evaluar los resultados clínicos del tratamiento quirúrgico de pacientes con estreñimiento crónico incontrolable con tratamiento médico. MATERIAL Y METODOS: Estudio descriptivo de pacientes con estreñimiento crónico severo tratados mediante miectomía anorrectal posterior (técnica de Lynn). Se recogen los resultados de los últimos 15 años, con periodo de seguimiento postoperatorio mínimo de 1 año. Se incluyen pacientes con larga historia de estreñimiento, refractarios a tratamiento médico. Pruebas complementarias: enema opaco, manometría anorrectal y biopsias rectales. El resultado clínico de la técnica se clasifica según los siguientes criterios: Curación: >3 movimientos intestinales por semana, sin incontinencia/encopresis y sin necesidad de tratamiento médico; Mejoría: >3 movimientos intestinales por semana, sin incontinencia/encopresis y con necesidad de laxante. RESULTADOS: Se realizaron 19 miectomías (edad media de 8,47 años). Tiempo medio de estreñimiento previo de 7,89 años. Los hallazgos en la anatomía patológica fueron: presencia de células ganglionares en 10, ausencia de células ganglionares en 4 y otras alteraciones en 5. Manometría en 6 pacientes, 4 presentaron reflejo inhibitorio anal. Cuatro pacientes se diagnosticaron de enfermedad de Hirschsprung (uno se curó con la miectomía, dos precisaron cirugía correctora y uno no acudió a revisiones). En los 15 restantes, cumplieron criterios de curación 8 pacientes (53,3%), 4 mejoraron (26,6%), 1 sin mejoría sigue tratamiento fisioterápico. Dos pacientes no continuaron las revisiones. No se registró incontinencia fecal ni otras complicaciones. CONCLUSIONES: La miectomía de Lynn es un procedimiento eficaz y seguro para los pacientes con estreñimiento crónico severo refractario al tratamiento médico. También resulta el tratamiento definitivo en la enfermedad de Hirschsprung de segmento ultracorto.

An experimental apparatus for the study of high-temperature degradation and solid-deposit formation of lubricants.

When exposed to high surface temperatures, engine lubricating oils degrade and may form solid deposits, which cause operational issues and increase shutdown time and maintenance costs. Despite its being a common issue in engine operation, the information available on the mechanics of this phenomenon is still lacking, and the experimental data and conditions must be updated to match the improvements in both lubricant stability and engine efficiency. To this end, an experimental apparatus has been developed to study the mechanisms that lead to the degradation and deposit formation of lubricants at high temperatures. The apparatus is designed to operate at pressures up to 69 bar, surface temperatures up to 650 °C, oil bulk temperatures up to 550 °C, and flow rates of <14 mL/min. In this apparatus, the oil is cycled through a heated test section, and deposits accumulate on the heated surface. The time required for deposits to start accumulating under the test conditions is determined based on the recorded temperature traces, and collected oil and deposit samples may be analyzed to determine changes in composition over time due to high-temperature exposure. The removable test section can be modified to accommodate different geometries, surface materials, and flow paths to adapt the instrument to a range of potential research directions. This paper presents the technical details of the new apparatus and the steps taken to characterize the experimental conditions. In addition, sample data are provided to show the unique capabilities of the new instrument, and an Arrhenius plot for Castrol Perfecto X 32 in the surface temperature range of 445-475 °C is presented as a demonstration of its use for quantifying the coking delay time. The new instrument detailed herein is the first such device to demonstrate a reliable, lab-scale technique for studying lube oil coke formation and deposition at temperatures and pressures of interest to power generation gas turbines.

Assessment of ITER radiation environment during the remote-handling operation of In-Vessel components with D1SUNED.

During ITER operational life, a remote-handled cask will be used to transfer In-Vessel components to the Hot Cell for maintenance, storage and decommissioning purposes. Due to the distribution of penetrations for system allocation in the facility, the radiation field of each transfer operation presents a high spatial variability; all operations must be studied independently for workers and electronics protection. In this paper, we present a fully representative approach to describe the radiation environment during the complete remote-handling scenario of In-Vessel components in the ITER facility. The impact of all relevant radiation sources during different stages of the operation is addressed. As-built structures and 2020 baseline designs are considered to produce the most detailed neutronics model of the Tokamak Complex, the 400,000-tonne civil structure hosting the tokamak, up to date. Novel capabilities of the D1SUNED code have allowed to compute the integral dose, the dose rate and the photon-induced neutron flux of both moving and static radiation sources. Time bins are included in the simulations to compute the dose rate caused by In-Vessel components at all positions along the transfer. The time evolution of the dose rate is built in video format with a 1-m resolution, especially valuable for hot-spots identification.

Assessment of the Relationship Between Inflammation and Glomerular Filtration Rate.

Background: Chronic kidney disease (CKD) is a global health problem. As it progresses to end stages, renal replacement therapy is required but ultimately, the best treatment is transplantation. Decreased renal function has been associated with an inflammatory state associated to primary CKD and in kidney transplant recipients (KTRs). Objective: To establish how the serum concentrations of some cytokines, such as interleukin (IL)-2, IL-8, IL-22, IL-17α, interferon-gamma, IL-4, and transforming growth factor-ß, correlate with various CKD stages. Methods: One hundred and forty-one KTRs between the ages of 18 and 75 years were included in the study. We also included 112 live kidney donors, 37 CKD PGCKD+3, and 76 GPhealthy. Participants were grouped according to their glomerular filtration rate (GFR) and their circulating cytokine levels, previously quantified by ELISA. Results: By linear regression analysis, we established the relation of each cytokine with the GFR. Transforming growth factor-ß correlated positively with the GFR in the study population, except in healthy individuals. A negative correlation of IL-8 and IL-17α and GFR was found in all cases. Conclusions: Whether these cytokines (IL-8 and IL-17α) could be used as inflammatory biomarkers indicating CKD progression, regardless of the type of population, remains to be prospectively determined.

Contexte: L'insuffisance rénale chronique (IRC) est un problème de santé mondial. Une thérapie de remplacement rénal est nécessaire au fur et à mesure que la maladie évolue vers les stades terminaux. Mais, en définitive, le meilleur traitement reste la transplantation. La réduction de la fonction rénale a été associée à un état inflammatoire associé à l'IRC primaire; une association observée aussi chez les receveurs d'une greffe de rein. Objectif: Déterminer la façon dont les concentrations sériques de certaines cytokines, notamment IL-2, IL-8, IL-22, IL-17a, IFN-γ, IL-4 et TGF-ß, corrèlent avec divers stades de l'IRC. Méthodologie: Ont été inclus dans l'étude 141 receveurs d'une greffe rénale âgés de 18 à 75 ans, 112 donneurs vivants de rein, 37 personnes atteintes d'IRC (PGIRC+3) et 76 personnes en bonne santé (PGen santé). Les sujets ont été regroupés en fonction de leur débit de filtration glomérulaire (DFGe) et de leur taux de cytokines en circulation, quantifiés préalablement par ELISA. Résultats: Une analyse de régression linéaire a servi à établir la relation entre chaque cytokine et le DFGe. Dans la population étudiée, une corrélation positive a été observée entre TGF-ß et le DFGe, sauf chez les individus sains. Dans tous les cas, la corrélation s'est avérée négative entre le DFGe et les taux d'IL-8 et d'IL-17a. Conclusion: Il reste à déterminer prospectivement si ces cytokines (IL-8 et IL-17a) pourraient être utilisées comme biomarqueurs inflammatoires pour indiquer la progression de l'IRC, quelle que soit la population.

Xylitol prevents NEFA-induced insulin resistance in rats.

AIMS/HYPOTHESIS: Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance. METHODS: We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic-hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol. RESULTS: Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol. CONCLUSIONS/INTERPRETATION: We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects.

Patterns in composition, abundance and scarring of whale sharks Rhincodon typus near Holbox Island, Mexico.

Photo-identification and conventional tagging were used to estimate population size and structure of the whale shark Rhincodon typus near Holbox Island, Mexico. From 2005 to 2008, photographs of spot patterns behind the last gill slit and in a lateral view on the left side of each animal were used to identify individuals. Additionally, 578 R. typus were tagged using conventional marker tags. Of these and the 350 R. typus that were identified from 1184 photographs, 65% were male; 27%, female and 8%, indeterminate sex. Photographed R. typus ranged in size from 2·5 to 9·5 m total length. Size was bimodal with a large peak at 6 m and a smaller peak at 7 m. Photo-identification showed that there was considerable loss of marker tags. Few of these remained on the animals for more than a year, so that interannual re-sights using tagging could not be used in population modelling. Forty six interannual re-sightings were found in the photographic library; the interval between these re-sightings was typically 1 year. It was estimated that the R. typus aggregation near Holbox Island ranged from 521 to 809 individuals, based on mark-recapture models. From 13 to 33% of R. typus photographed had scars that were attributable to boat strikes. This study provides a baseline for assessing the status of R. typus near Holbox Island. This information is useful to understand drivers of local population size and distribution and potential concerns about increasing effects of tourism on R. typus in this area and for designing better management programmes for R. typus conservation.

Microbialites show a distinct cyanobacterial phylogenetic structure and functional redundancy in Bacalar lagoon and Cenote Azul sinkhole, Yucatan Peninsula, Mexico.

Cyanobacterial components of microbialites from two geographically close systems, the Bacalar lagoon (BL) and the Cenote Azul sinkhole (CA) in Quintana Roo, Mexico, were characterized. BL and CA systems were studied along a longitudinal gradient (north to south) and a depth gradient (5-30 m), respectively. Microscopic observations, 16S rRNA amplicon sequencing, and shotgun metagenomics were used to characterize Cyanobacteria. Both systems showed similar metabolic/functional profiles but harbored completely different cyanobacterial taxa. BL was dominated by Nostocales, including a population of previously undescribed Chakia sp., while CA was dominated by an unknown taxon of Chroococcales, comprising 70% of relative abundance through all depths. Interestingly, cyanobacterial assemblages in microbialites exhibited phylogenetic overdispersion in most of the BL sites, while CA sites exhibited phylogenetic clustering, these differences were attributed to depth/light conditions and possibly different times of geological formation for BL and CA systems.

Prevalence of sensitization to lipid transfer proteins and profilins in a population of 430 patients in the south of Madrid.

BACKGROUND: Lipid transfer proteins (LTPs) and profilins are the most important panallergens in the management of patients who are allergic to pollen and plant food in our area. LTPs are highly stable proteins that can induce systemic symptoms after ingestion. Profilins are labile proteins that are present in pollens and vegetables. Considered markers of several types of pollen sensitization, they are responsible for cross-reactivity between pollens and vegetables. The objective of this study was to assess the frequency of sensitization to LTP and profilin using skin prick tests (SPTs) in patients referred to our allergy unit for any complaint (not only pollen and plant food allergy). METHODS: The study sample comprised 430 consecutive patients who were evaluated using their medical history and SPTs with pollen, date palm profilin, and peach extract enriched in Pru p 3 (30 g/mL) as an LTP marker. RESULTS: We found that 52 (12.1%) patients were sensitized to profilin and 53 (12.3%) to LTP. Pollen allergy was diagnosed in 53% and plant food allergy in 11%. In the LTP-sensitized group and the profilin-sensitized group, 37.7% and 34.6% of the patients had plant food allergy, respectively. Thirty-three patients (62.3%) were sensitized to LTP but had no symptoms after eating vegetables. CONCLUSIONS: To the best of our knowledge, this is the first study to analyze the real rate of sensitization to profilin and LTP in a population sensitized to allergens other than pollens and plant foods. Twelve percent of patients were sensitized to both profilin and LTP. A large proportion of LTP-sensitized patients had no symptoms at the time of the study.

Early Posttransplant Blood Transfusion and Risk for Worse Graft Outcomes.

INTRODUCTION: Blood transfusion is a risk factor for allosensitization. Nevertheless, blood transfusion posttransplant remains a common practice. We evaluated the effect of posttransplant blood transfusion on graft outcomes. METHODS: We included nonsensitized, first-time, kidney-alone recipients transplanted between 1 July 2015 and 31 December 2017. Patients were grouped based on receiving blood transfusion in the first 30 days posttransplant. The primary end point was a composite outcome of biopsy-proven acute rejection, death of any cause, or graft failure in the first year posttransplant. Secondary outcomes included the individual components of the primary outcome and the cumulative incidence of de novo donor-specific antibodies (DSAs). RESULTS: Two hundred seventy-three patients were included. One hundred twenty-seven (47%) received blood transfusion. Patients in the transfusion group were more likely to be older, have had a deceased donor, and have received induction with basiliximab. There was no difference between groups in the composite primary outcome (adjusted hazard ratio = [HR] 1.34; 95% confidence interval [CI], 0.83-2.17; P = 0.23). The cumulative incidence of de novo DSAs during the first year posttransplant was similar between groups (12.8% transfusion vs. 10.9% no transfusion, P = 0.48). CONCLUSION: Early transfusion of blood products in kidney transplant recipients receiving induction with lymphocyte depletion was not associated with an increased hazard of experiencing acute rejection, death from any cause, or graft loss.

APOL1 Risk Variants and Acute Kidney Injury in Black Americans with COVID-19.

BACKGROUND AND OBJECTIVES: Black Americans have a higher incidence of kidney disease compared with populations that do not have recent African ancestry. Two risk variants in the APOL1 are responsible for a portion of this higher risk. We sought to assess the odds of AKI conferred by APOL1 risk alleles in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Black Americans who tested positive for coronavirus disease 2019 (COVID-19) were genotyped to determine APOL1 risk allele status. We assessed the incidence of AKI, persistent AKI, and AKI requiring KRT within 21 days of the PCR-based diagnosis. Outcomes were adjusted for age, sex, body mass index, hypertension, eGFR, and use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. RESULTS: In total, 126 cases of SARS-CoV-2 infection were included within a 5-month period, with 16 (13%) and 110 (87%) cases with two and zero/one APOL1 high-risk alleles, respectively. AKI occurred in 11 (69%) patients with two APOL1 high-risk alleles and 39 (35%) patients with zero/one high-risk alleles (adjusted odds ratio, 4.41; 95% confidence interval, 1.11 to 17.52; P=0.04). Persistent AKI occurred in eight (50%) patients with two APOL1 high-risk alleles and 21 (19%) of those with zero/one high-risk alleles (adjusted odds ratio, 3.53; 95% confidence interval, 1.8 to 11.57; P=0.04). AKI KRT occurred in four (25%) of those with two APOL1 high-risk alleles and eight (7%) of those with zero/one high-risk alleles (adjusted odds ratio, 4.99; 95% confidence interval, 1.02 to 24.4, P=0.05). CONCLUSIONS: APOL1 high-risk alleles are associated with greater odds of AKI in Black American patients with COVID-19.

Lost in Transportation: Calcium Oxalate Crystals in Kidney Biopsy Specimens Fixed in Michel Medium May Disappear.

CONTEXT.­: Calcium oxalate (CaOx) deposits in a kidney biopsy specimen can be seen in acute or chronic kidney injury and in oxalate nephropathy. Although no established cutoff criteria to diagnose oxalate nephropathy versus incidental CaOx deposition in the kidney exist, these conditions require different treatment. We noticed a significant decrease in the number of CaOx deposits in the kidney biopsy cores that were fixed in Michel transport medium (MTM) as compared to their counterparts fixed in formalin. OBJECTIVE.­: To investigate the impact of different fixatives on the number of CaOx deposits in kidney biopsy specimens. DESIGN.­: Retrospective search for kidney biopsies with diagnosis of CaOx deposition was performed in our Renal Pathology Database between January 1, 2015 and October 15, 2018. RESULTS.­: Seventy-six biopsies with an increased number of CaOx deposits were identified. CaOx deposits were counted on slides from the frozen tissue (MTM fixed or fresh frozen) and from the formalin-fixed cores. The density of CaOx deposits was significantly higher in formalin-fixed cores (13.6 ± 10.0/cm) than in MTM-fixed cores (3.2 ± 5.1/cm; P < .001). CaOx density in the kidney biopsy specimens decreased progressively with increased fixation time in MTM. No significant differences in the CaOx density between formalin-fixed and fresh frozen tissue were observed. CONCLUSIONS.­: Our data demonstrate that fixation in MTM may result in a significant reduction in the number of CaOx deposits in a kidney biopsy specimen. This may make the diagnosis difficult, especially in small biopsy specimens with limited tissue in the formalin-fixed paraffin block.