Nephrotoxicity Associated with Cytoreductive Surgery Combined with Cisplatin-Based Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignant Disease: A Systematic Review and Meta-Analysis.

Background: Cisplatin is employed in hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) for peritoneal surface malignancies (PSMs). The main concern regarding intraperitoneal cisplatin administration is nephrotoxicity. Numerous reports in this context are available. Our objective was to conduct a systematic review and meta-analysis to assess cisplatin-based HIPEC-related nephrotoxicity (CHRN). Methods: A systematic literature review on CHRN after CRS for the treatment of PSMs was performed. The literature search was carried out using Medline, Cochrane, and Embase. The last day of the search was 23 October 2023. PRISMA guidelines were used. A meta-analysis was then conducted. The main endpoint was the incidence of acute and chronic renal impairment after CHRN. Secondary endpoints included the potential impact of several clinical variables on the primary endpoint and a critical appraisal of the different renal impairment scales employed. Results: Our study included 26 articles with a total sample of 1473 patients. The incidence of acute kidney injury (AKI) was 18.6% (95% CI: 13.6-25%, range of true effects 3-59%). For chronic kidney disease, it was 7% (95% CI: 3-15.3%, range of true effects 1-53%). The variables that statistically influenced these results were the scale used to measure renal insufficiency, the use of nephroprotective agents, and the presence of pre-existing renal disease. Conclusions: The reported incidence of renal impairment following cisplatin-based HIPEC is highly variable. The incidence of renal failure obtained in this meta-analysis should be used as a reference for subsequent reports on this topic. Further prospective studies are warranted to establish optimal and standardized management.

Acceptability of Long-Acting Injectable Antiretroviral Treatment for HIV Management: Perspectives of Patients and Physicians in Spain.

We assessed the prevalence and factors associated with HIV-infected patients' interest in trying long-acting injectable antiretroviral treatment (LAI-ART) along with its expected benefits and concerns, and evaluated physicians' opinions about LAI-ART. This study was set within the multi-center prospective CoRIS cohort, comprising HIV-positive adults, naïve to antiretroviral treatment (ART) at study entry, recruited from 2004 onward in 48 centers in Spain. In June 2022, we conducted a 2-day cross-sectional survey among patients across 34 CoRIS centers and sent an online questionnaire to all physicians prescribing ART in 39 CoRIS centers. Of the 271 patients included, 83.3% [95% confidence interval (CI)]: 78.0 - 87.0%) expressed interest in receiving LAI-ART. This interest was higher among men (adjusted odds ratio: 2.96; 95% CI: 1.4-6.12), those aged <50 years (2.41; 1.23 - 4.73), and individuals inconvenienced by oral ART (5.03; 1.47 - 17.15), daily intake (14.65; 3.44-62.46), carrying HIV pills constantly (7.19; 2.88 - 17.96), and taking multiple medications (3.94; 1.58 - 9.85). Among the 154 physicians surveyed, 45.5% believed LAI-ART would be the preferred option for patients. Although most physicians (92.9%) thought LAI-ART could improve patients' quality of life (QoL), concerns were raised by 37.7% and 44.2% of them regarding injection site pain and visit rescheduling, respectively. Interest in LAI-ART was higher among men, those aged <50 years, and individuals finding their oral ART inconvenient. Physicians believed LAI-ART could improve QoL and overcome treatment challenges, yet concerns were raised about its potential usage difficulties. Although most patients were interested in receiving LAI-ART, only less than half of the physicians considered it their preferred option, likely owing to concerns about missed visits and injection site pain.

Transition times across the HIV care continuum in Spain from 2005 to 2022: a longitudinal cohort study.

BACKGROUND: Ending AIDS by 2030 requires improvements across all stages of the HIV care continuum. We used a longitudinal approach to assess changes in the HIV care continuum in Spain and transition probabilities across different stages. METHODS: We used data from the prospective Cohort of the Spanish HIV/AIDS Research Network to analyse the time from diagnosis to linkage to care, linkage to care to antiretroviral therapy (ART), and ART to viral suppression in five calendar periods defined by milestones in ART, from 2005 to 2022. We used the Kaplan-Meier method and Cox proportional hazard models to estimate cumulative probabilities of stage transition within 1, 3, 6, and 12 months of stage eligibility, by period. FINDINGS: We included 18 529 participants. Comparing the initial (2005-09) and final (2020-22) periods, time to linkage to care decreased from a median of 6·0 weeks to 1·3 weeks, time to ART initiation from 15·9 weeks to 0·4 weeks, and time to viral suppression from 13·3 weeks to 7·1 weeks. Adjusted hazard ratios for the comparison between the last period and the initial period were 3·1 (95% CI 2·8-3·4) for linkage to care within 1 month, 11·4 (10·1-12·3) for ART initiation within 1 month, and 2·2 (1·2-2·4) for viral suppression within 3 months. The aggregate proportion of late diagnoses was 38·6%, increasing after 2012 to 46·4% in the 2020-22 period. Same-day ART initiation increased from 18% to 39% from 2005 to 2022. The overall incidence rate of virological failure was 1·05 failures per 1000 person-years and showed a non-significant decline throughout the study. INTERPRETATION: The great improvement in transition times through the HIV care cascade might put Spain on the verge of achieving the UNAIDS targets for HIV elimination. However, late diagnosis remains a challenge that should be addressed. FUNDING: Instituto de Salud Carlos III and Spanish AIDS Research Network.

High concentrations of Maraviroc do not alter immunological and metabolic parameters of CD4 T cells.

Maraviroc (MVC) is an antiretroviral drug capable of binding to CCR5 receptors and block HIV entry into target cells. Moreover, MVC can activate NF-kB pathway and induce viral transcription in HIV-infected cells, being proposed as a latency reversal agent (LRA) in HIV cure strategies. However, the evaluation of immunological and metabolic parameters induced by MVC concentrations capable of inducing HIV transcription have not been explored in depth. We cultured isolated CD4 T cells in the absence or presence of MVC, and evaluated the frequency of CD4 T cell subpopulations and activation markers levels by flow cytometry, and the oxidative and glycolytic metabolic rates of CD4 T cells using a Seahorse Analyzer. Our results indicate that a high concentration of MVC did not increase the levels of activation markers, as well as glycolytic or oxidative metabolic rates in CD4 T cells. Furthermore, MVC did not induce significant changes in the frequency and activation levels of memory cell subpopulations. Our data support a safety profile of MVC as a promising LRA candidate since it does not induce alterations of the immunological and metabolic parameters that could affect the functionality of these immune cells.

Ibrutinib and R-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma of non-GCB type: Phase II clinical trial of the Spanish GELTAMO group.

PURPOSE: This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem cell transplantation. Patients received an induction treatment consisting of 6 or 8 cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles. RESULTS: Sixty-four patients were included, 72% of them refractory to the last regimen. The ORR and CR rate after the 4th cycle were 53% (95% confidence interval [CI], 41-65) and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year PFS and OS were 18% (95% CI, 8 - 28) and 26% (95% CI, 14 - 37), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (44%), neutropenia (30%) and anemia (14%). Grade ≥3 infectious and cardiovascular TRAEs were reported in 6 (9%) and 1 (2%) patient, respectively. CONCLUSIONS: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.

Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.

BACKGROUND: Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown. METHODS: We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional in vitro experiments. RESULTS: This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation. CONCLUSION: Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis.

BACKGROUND: Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients. METHODS: We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5). RESULTS: By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group. CONCLUSION: Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary.

Real-life application of a stratification model for HIV care.

INTRODUCTION: HIV infection has become a chronic disease with a good long-term prognosis, necessitating a change in the care model. For this study, we applied a proposal for an Optimal Care Model (OCM) for people with HIV (PHIV), which includes tools for assessing patient complexity and their classification into profiles to optimize care provision. METHODS: Observational, cross-sectional, and retrospective study. Adult PHIV treated at the Tropical Medicine consultations at Ramón y Cajal Hospital from January 1 to June 30, 2023, were included. The complexity calculation and the stratification into profiles for each patient were done according to the OCM. RESULTS: Ninety-four participants were included, 76.6% cisgender men, with a median age of 41 years (range 23-76). Latin America and Africa were the main regions of origin (72.4%). 98% had an undetectable HIV viral load. The degree of complexity was 78.7% low, 11.7% medium, 1% high, and 8.5% extreme. The predominant profile was blue (64.9%), followed by lilac (11.7%), purple (6.3%), and green (4.3%). 7.4% were unclassifiable, of whom 57.2% had high/extreme complexity. Among the unclassifiable, mental health problems were the most common. CONCLUSIONS: The OCM tools for People Living with HIV (PLWH) allow for the classification and stratification of most patients in a consultation with a non-standard population. Patients who did not fit into the pre-established profiles presented high complexity. Creating a profile focused on mental health or mixed profiles could facilitate the classification of more patients.

Hipertensión portal no cirrótica por enfermedad vascular porto-sinusoidal: presentación de un caso y revisión de la literatura / Non-cirrhotic portal hypertension due to porto-sinusoidal vascular disease: Case presentation and literature review

La enfermedad vascular porto-sinusoidal es una causa infrecuente de hipertensión portal no cirrótica, fue descrita recientemente y es poco diagnosticada por el desconocimiento entre los médicos. Se considera en casos de hipertensión portal clínicamente significativa, en ausencia de cirrosis. El diagnóstico se basa en los hallazgos de la biopsia. El pronóstico de la enfermedad es mejor que el de los pacientes cirróticos, y el tratamiento es similar al de la hipertensión portal y al de las complicaciones que presentan los pacientes con cirrosis. Se presenta el caso de una paciente con várices esofágicas con estudios de imágenes no compatibles con cirrosis y hallazgos específicos en la biopsia de enfermedad vascular porto-sinusoidal. Este caso muestra el ejercicio diagnóstico en un caso de enfermedad vascular porto-sinusoidal de una paciente de Colombia, así como el resultado de las intervenciones terapéuticas y la evolución en el tiempo.

Porto-sinusoidal vascular disease is an uncommon cause of non-cirrhotic portal hypertension. It was recently described and is rarely diagnosed due to lack of knowledge among doctors. It is considered in cases of clinically significant portal hypertension in the absence of cirrhosis, and the diagnosis is based on biopsy findings. The prognosis of the disease is better than that of cirrhotic patients, and the treatment is similar to that of portal hypertension, including the management of complications associated with cirrhosis. We present the case of a patient with esophageal varices, whose imaging studies were not compatible with cirrhosis, alongside specific biopsy findings of porto-sinusoidal vascular disease. This case illustrates the diagnostic process in a patient from Colombia with portosinusoidal vascular disease, as well as the outcomes of therapeutic interventions and the patient´s evolution over time.

Mitochondrial Haplogroups and Weight Gain After Initiating ART in Patients with HIV.

We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1,019 treatment-naïve persons with HIV (PWH) who initiated first-line antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90 Kg and 0.98 Kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH.

Kikuchi–Fujimoto disease type lymph node reaction with increased plasmacytoid dendritic cells may appear as a side effect following COVID-19 vaccination: Report of a case and literature review / Linfadenitis de tipo Kikuchi-Fujimoto con expansión de células dendríticas plasmocitoides como evento adverso asociado a la vacunación por COVID-19. Reporte de un caso y revisión de la literatura

Subsequent to mass vaccination programs against COVID-19, diverse side effects have been described, both at the injection site, such as pain, redness and swelling, and systemic effects such as fatigue, headache, muscle or joint pain. On rare occasions, a lymphadenopathic syndrome may develop, raising the clinical suspicion of a lymphoproliferative disorder. We present the case of a 30-year-old woman who developed self-limiting left axillary lymphadenopathy following COVID-19 vaccination. To date, only seven similar cases with a complete clinicopathological description have been published, and fourteen cases have been notified to the European adverse events databases (Eudravigilance) in relationship with vaccination against COVID-19. It is important to be aware of this potential complication when a lymphadenopathic syndrome develops following vaccination, to avoid unnecessary treatment. (AU)

Tras la vacunación masiva frente a la COVID-19 se han comenzado a describir diversos efectos adversos incluyendo efectos locales en el lugar de la inyección, como dolor, enrojecimiento, hinchazón, etc., y efectos sistémicos como fatiga, dolor de cabeza, dolor muscular o articular. Más infrecuentemente se pueden desarrollar cuadros linfadenopáticos sospechosos clínicamente de proceso linfoproliferativo. Presentamos el caso de una mujer de 30 años que desarrolló linfadenopatía axilar izquierda tras la vacunación contra la COVID-19 con hallazgos histopatológicos de linfadenopatía necrotizante de tipo Kikuchi y resolución espontánea. Hasta el momento se han publicado 7 casos con descripción clinicopatológica completa en la literatura y notificado 14 casos en la Red Europea de Farmacovigilancia en relación con la vacunación. Es importante tener en cuenta esta entidad en linfadenopatías sospechosas de procesos linfoproliferativos en este contexto, para evitar un tratamiento innecesario. (AU)

Corrigendum: CD4/CD8 ratio and CD8+ T-cell count as prognostic markers for non-AIDS mortality in people living with HIV. A systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fimmu.2024.1343124.].

A Phase I/IIa Prospective, Randomized, Open-Label Study on the Safety and Efficacy of Nebulized Liposomal Amphotericin for Invasive Pulmonary Aspergillosis.

Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/µL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (-3.6 vs. -0.95, p: 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary.

Kikuchi–Fujimoto disease type lymph node reaction with increased plasmacytoid dendritic cells may appear as a side effect following COVID-19 vaccination: Report of a case and literature review / Linfadenitis de tipo Kikuchi-Fujimoto con expansión de células dendríticas plasmocitoides como evento adverso asociado a la vacunación por COVID-19. Reporte de un caso y revisión de la literatura

Subsequent to mass vaccination programs against COVID-19, diverse side effects have been described, both at the injection site, such as pain, redness and swelling, and systemic effects such as fatigue, headache, muscle or joint pain. On rare occasions, a lymphadenopathic syndrome may develop, raising the clinical suspicion of a lymphoproliferative disorder. We present the case of a 30-year-old woman who developed self-limiting left axillary lymphadenopathy following COVID-19 vaccination. To date, only seven similar cases with a complete clinicopathological description have been published, and fourteen cases have been notified to the European adverse events databases (Eudravigilance) in relationship with vaccination against COVID-19. It is important to be aware of this potential complication when a lymphadenopathic syndrome develops following vaccination, to avoid unnecessary treatment. (AU)

Tras la vacunación masiva frente a la COVID-19 se han comenzado a describir diversos efectos adversos incluyendo efectos locales en el lugar de la inyección, como dolor, enrojecimiento, hinchazón, etc., y efectos sistémicos como fatiga, dolor de cabeza, dolor muscular o articular. Más infrecuentemente se pueden desarrollar cuadros linfadenopáticos sospechosos clínicamente de proceso linfoproliferativo. Presentamos el caso de una mujer de 30 años que desarrolló linfadenopatía axilar izquierda tras la vacunación contra la COVID-19 con hallazgos histopatológicos de linfadenopatía necrotizante de tipo Kikuchi y resolución espontánea. Hasta el momento se han publicado 7 casos con descripción clinicopatológica completa en la literatura y notificado 14 casos en la Red Europea de Farmacovigilancia en relación con la vacunación. Es importante tener en cuenta esta entidad en linfadenopatías sospechosas de procesos linfoproliferativos en este contexto, para evitar un tratamiento innecesario. (AU)

CD4/CD8 ratio and CD8+ T-cell count as prognostic markers for non-AIDS mortality in people living with HIV. A systematic review and meta-analysis.

Background: In people living with HIV (PLHIV), the CD4/CD8 ratio has been proposed as a useful marker for non-AIDS events. However, its predictive ability on mortality over CD4 counts, and the role of CD8+ T-cell counts remain controversial. Methods: We conducted a systematic review and meta-analysis of published studies from 1996 to 2023, including PLHIV on antiretroviral treatment, and reporting CD4/CD8 ratio or CD8+ counts. The primary outcome was non-AIDS mortality or all-cause mortality. We performed a standard random-effects pairwise meta-analysis comparing low versus high CD4/CD8 ratio with a predefined cut-off point of 0.5. (CRD42020170931). Findings: We identified 2,479 studies for screening. 20 studies were included in the systematic review. Seven studies found an association between low CD4/CD8 ratio categories and increased mortality risk, with variable cut-off points between 0.4-1. Four studies were selected for meta-analysis, including 12,893 participants and 618 reported deaths. Patients with values of CD4/CD8 ratio below 0.5 showed a higher mortality risk (OR 3.65; 95% CI 3.04 - 4.35; I2 = 0.00%) compared to those with higher values. While the meta-analysis of CD8+ T-cell counts was not feasible due to methodological differences between studies, the systematic review suggests a negative prognostic impact of higher values (>1,138 to 1,500 cells/uL) in the long term. Conclusions: Our results support the use of the CD4/CD8 ratio as a prognostic marker in clinical practice, especially in patients with values below 0.5, but consensus criteria on ratio timing measurement, cut-off values, and time to event are needed in future studies to get more robust conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020170931, identifier CRD42020170931.

Strategies to Reduce the Use of Antibiotics in Fresh and Chilled Equine Semen.

The study assessed the impact of four equine semen processing techniques on sperm quality and microbial load immediately post-processing and after 48 h of refrigeration. The aim was to explore the potential reduction of prophylactic antibiotic usage in semen extenders. Semen from ten adult stallions was collected and processed under a strict hygiene protocol and divided into four aliquots: Simple Centrifugation with antibiotics (SC+), Simple Centrifugation (SC-), Single-Layer Colloidal Centrifugation (CC-), and Filtration (with SpermFilter®) (F-), all in extenders without antibiotics. Sperm motility, viability, and microbial load on three culture media were assessed. No significant differences were observed in the main in the sperm quality parameters among the four protocols post-processing and at 48 h (p < 0.05 or p < 0.1). Microbial loads in Columbia 5% Sheep Blood Agar and Schaedler vitamin K1 5% Sheep Blood Agar mediums were significantly higher (p < 0.10) for raw semen than for CS+, CC-, and F- post-processing. For Sabouraud Dextrose Agar medium, the microbial load was significantly higher (p < 0.10) in raw semen compared to CS+ and F-. No significant differences (p < 0.10) were found in 48 h chilled samples. Regardless of antibiotic presence, the evaluated processing methods, when combined with rigorous hygiene measures, maintained semen quality and reduced microbial load to the same extent as a traditional protocol using antibiotics.

Kikuchi-Fujimoto disease type lymph node reaction with increased plasmacytoid dendritic cells may appear as a side effect following COVID-19 vaccination: Report of a case and literature review.

Subsequent to mass vaccination programs against COVID-19, diverse side effects have been described, both at the injection site, such as pain, redness and swelling, and systemic effects such as fatigue, headache, muscle or joint pain. On rare occasions, a lymphadenopathic syndrome may develop, raising the clinical suspicion of a lymphoproliferative disorder. We present the case of a 30-year-old woman who developed self-limiting left axillary lymphadenopathy following COVID-19 vaccination. To date, only seven similar cases with a complete clinicopathological description have been published, and fourteen cases have been notified to the European adverse events databases (Eudravigilance) in relationship with vaccination against COVID-19. It is important to be aware of this potential complication when a lymphadenopathic syndrome develops following vaccination, to avoid unnecessary treatment.

From Castleman disease histopathological features to idiopathic multicentric Castleman disease: a multiparametric approach to exclude potential iMCD histopathological mimickers.

AIMS: International consensus diagnostic criteria for idiopathic multicentric Castleman disease (iMCD) includes lymph node Castleman disease (CD) histopathological features as major criteria. Our aim was to apply those criteria in a series of 42 cases with CD to find differences among unicentric CD, iMCD, HHV-8+multicentric CD (HHV-8+MCD) and POEMS/plasma cell neoplasia (PCN)-associated CD. METHODS: Available clinical and laboratory criteria were collected. Histopathological features (germinal centre hyperplasia/regression, plasmacytosis, hypervascularity and follicular dendritic cell (FDC) prominence) were graded and immunohistochemistry with antibodies against CD20, CD3, CD138, HHV-8, Ig isotype (IgG, IgG4, IgA, IgM, IgD), kappa, lambda was performed in all cases. RESULTS: Fourteen cases had hyaline-vascular type unicentric CD, 15 were HHV-8+MCD, 7 cases PCN/POEMS-associated CD and 5 cases were iMCD. One case was consistent with systemic lupus erythematosus (SLE) lymphadenopathy. Differences in grading of the CD-associated histopathological features showed that FDC proliferation was prominent in unicentric CD, hypervascularity was increased in HHV-8 positive MCD and germinal centre hyperplasia was restricted to iMCD cases and SLE. Monotypic plasma cells were readily identifiable in the lymph node biopsies in 43% of PCN/POEMS-associated CD. All three cases had lambda light chain restriction with IgA (two cases) and IgG (one case) isotypes. CONCLUSIONS: HHV-8+ MCD and PCN/POEMS-related CD are the major mimickers of iMCD in lymph node biopsies. Grading of the five histopathological features for CD might be useful to, in conjunction with complete ancillary testing, suggest for specific disease entities.

Feasibility of a selective targeted strategy of HIV testing in emergency departments: a before-after study.

BACKGROUND AND IMPORTANCE: The rates of hidden infection and late diagnosis of HIV still remain high in Western countries. Missed diagnostic opportunities represent the key point in changing the course of the epidemic. OBJECTIVE: To evaluate the feasibility and results of implementation of a selective strategy to test for HIV in the emergency department (ED) in patients with six pre-defined medical situations: sexually transmitted infections, herpes zoster, community-acquired pneumonia, mononucleosis syndrome, practice of chemsex (CS) or request of post-exposure prophylaxis. DESIGN: This quasi-experimental longitudinal study evaluated the pre- and post-implementation results of HIV testing in the six aforementioned clinical scenarios. SETTINGS AND PARTICIPANTS: Patients attended 34 Spanish EDs. INTERVENTION OR EXPOSURE: The intervention was an intensive educational program and pathways to facilitate and track orders and results were designed. We collected and compared pre- and post-implementation ED census and diagnoses, and HIV tests requested and results. OUTCOME MEASURES AND ANALYSIS: The main outcome was adherence to the recommendations. Secondary outcomes were to evaluate the effectiveness of the program by the rate of positive test and the new HIV diagnoses. Differences between first and second periods were assessed. The magnitude of changes (absolute and relative) was expressed with the 95% confidence interval (CI). MAIN RESULTS: HIV tests increasing from 7080 (0.42% of ED visits) to 13 436 (relative increase of 75%, 95% CI from 70 to 80%). The six conditions were diagnosed in 15 879 and 16 618 patients, and HIV testing was ordered in 3393 (21%) and 7002 (42%) patients (increase: 97%; 95% CI: 90-104%). HIV testing significantly increased for all conditions except for CS. The positive HIV test rates increased from 0.92 to 1.67%. Detection of persons with undiagnosed HIV increased from 65 to 224, which implied a 220% (95% CI: 143-322%) increase of HIV diagnosis among all ED comers and a 71% (95% CI: 30-125%) increase of positive HIV tests. CONCLUSION: Implementation of a strategy to test for HIV in selective clinical situations in the ED is feasible and may lead to a substantial increase in HIV testing and diagnoses.