Prevalence and genetic diversity of azole-resistant Malassezia pachydermatis isolates from canine otitis and dermatitis: a two-year study.

Despite previous reports on the emergence of Malassezia pachydermatis strains with decreased susceptibility to azoles, there is limited information on the actual prevalence and genetic diversity of azole-resistant isolates of this yeast species. We assessed the prevalence of azole resistance in M. pachydermatis isolates from cases of dog otitis or skin disease attended in a veterinary teaching hospital during a 2-year period and analyzed the ERG11 (encoding a lanosterol 14-α demethylase, the primary target of azoles) and whole genome sequence diversity of a group of isolates that displayed reduced azole susceptibility. Susceptibility testing of 89 M. pachydermatis isolates from 54 clinical episodes (1-6 isolates/episode) revealed low minimum inhibitory concentrations (MICs) to most azoles and other antifungals, but 11 isolates from six different episodes (i.e., 12.4% of isolates and 11.1% of episodes) had decreased susceptibility to multiple azoles (fluconazole, itraconazole, ketoconazole, posaconazole, ravuconazole, and/or voriconazole). ERG11 sequencing of these 11 azole-resistant isolates identified eight DNA sequence profiles, most of which contained amino acid substitutions also found in some azole-susceptible isolates. Analysis of whole genome sequencing (WGS) results revealed that the azole-resistant isolates from a same episode of otitis, or even different episodes affecting a same animal, were more genetically related to each other than to isolates from other dogs. In conclusion, our results confirmed the remarkable ERG11 sequence variability in M. pachydermatis isolates of animal origin observed in previous studies and demonstrate the value of WGS for disentangling the epidemiology of this yeast species.

We analyzed the prevalence and diversity of azole-resistant Malassezia pachydermatis isolates in a veterinary hospital. A low prevalence of multi-azole resistance (c.10% of isolates and cases) was found. Whole genome and ERG11 sequencing of resistant isolates revealed remarkable genetic diversity.

Prevalence of people living with multidrug-resistant HIV and limited treatment options in Spain.

OBJECTIVES: Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) with multidrug resistance (MDR; confirmed resistance to three or more [or resistance to two or more plus contraindication to one or more] core ART classes) and limited treatment options (LTOs) in Spain. METHODS: This was an observational, retrospective, multicentre, cross-sectional chart review study undertaken in five reference Spanish centres. Participants were people with HIV on ART with MDR and LTOs (detectable viral load [HIV-RNA >200 copies/mL], treatment-limiting drug-drug interaction [DDI], or intolerance precluding the use of one or more ART classes). Prevalence, demographic/clinical characteristics, and treatment options were assessed. Logistic regression analyses were used to identify MDR-associated variables. RESULTS: Of 14 955 screened people with HIV, 69 (0.46%) presented with MDR and 23 (0.15%) had LTOs. The population analysed was 73.9% male with a median age of 54.0 years; the median time since HIV diagnosis was 26.5 years, and median CD4+ cell count was 511.0 cells/µL. The only factor significantly associated with MDR (univariate analysis) was CD4+ cell count. Injection drug use was the most common transmission route. Comorbidities (mainly endocrine and cardiovascular disorders; 34.8% affecting HIV management) and concomitant treatments were frequent. No recent opportunistic infections were reported. Patients had been exposed to the following ART: nucleoside analogue reverse transcriptase inhibitors (100%), protease inhibitors (95.6%), non-nucleoside analogue reverse transcriptase inhibitors (87.0%), and integrase strand transfer inhibitors (82.6%). The available fully active drugs were dolutegravir (39.1%), bictegravir (30.4%), and raltegravir (21.7%). CONCLUSIONS: The prevalence of people with HIV with MDR and LTOs in Spain is very low, with approximately half of those studied not exhibiting virological suppression. Low CD4+ cell counts were associated with MDR. These findings may help address the impact and treatment needs of these patients and prevent clinical progression and transmission of MDR HIV.

Enhanced recovery after cardiac surgery: A literature review.

Enhanced recovery after cardiac surgery (ERACS) represents a constellation of evidence-based peri-operative methods aimed to reduce the physiological and psychological stress patients experience after cardiac surgery, with the primary objective of providing an expedited recovery to pre-operative functional status. The method involves pre-operative, intra-operative, and post-operative interventions as well as direct patient engagement to be successful. Numerous publications in regard to the benefits of enhanced recovery have been presented, including decreased post-operative complications, shortened length of stay, decreased overall healthcare costs, and higher patient satisfaction. Implementing an ERACS program undeniably requires a culture change, a methodical shift in the approach of these patients that ultimately allows the team to achieve the aforementioned goals; therefore, team-building, planning, and anticipation of obstacles should be expected.

Active surveillance of antimicrobial resistance in companion animals: A pilot study in a Spanish Veterinary Teaching Hospital.

The role of small animal veterinary hospitals in the onset and dissemination of antimicrobial-resistant organisms (AMROs) is still not clear, and the implementation of an internal surveillance systems is a cost-effective tool to better understand their impact. The aim of this study was to describe a pilot program of active surveillance in a Spanish Veterinary Teaching Hospital, developed to estimate the detection frequency of AMROs in the commensal flora of patients and in the environment. Surveillance was focused on Methicillin-resistant Staphylococci (MRS), third generation cephalosporins resistant gram-negative bacteria (3GCR-GNB), and carbapenems-resistant gram-negative bacteria (CR-GNB). Oral and perirectal swabs were collected in the same dogs and cats hospitalized > 48 h, at their admission and before their discharge. Out of 50 patients sampled, 24% (12/50) were carriers at admission of at least one of the three investigated AMROs. Twenty-eight percent of patients (14/50) acquired at least one AMRO during the hospital stay. MRS detection frequency at admission was 12% (6/50), while acquisition was 6% (3/50). 3GCR-GNB detection frequency was 14% at admission (7/50) and acquisition 22% (11/50), while CR-GNB detection frequency was 2% at admission (1/50) and acquisition 2% (1/50). Environmental surveillance (98 samples) showed a total detection frequency of 22.4% for MRS (22/98), 2% for 3GCR-GNB and CR-GNB (2/98). Clinical staff' shoe soles showed high detection frequency for MRS (50%). 3GCR Escherichia coli was the most isolated species in patients (n = 17). The results show how active surveillance can be used as a tool to assess the impact of AMROs in veterinary hospitals to subsequently build up tailored control plans based on specific issues.

Looking into the Eyes to See the Heart of Chronic Kidney Disease Patients.

In patients with chronic kidney disease (CKD), the main cause of morbidity and mortality is cardiovascular disease (CVD). Both coronary artery calcium scoring by computed tomography (CT) and optical coherence tomography (OCT) are used to identify patients at increased risk for ischemic heart disease, thereby indicating a higher cardiovascular risk profile. Our study aimed to investigate the utility of these techniques in the CKD population. In patients with CKD, OCT was used to measure the choroidal thickness (CHT) and the thickness of the peripapillary retinal nerve fiber layer (pRNFL). A total of 127 patients were included, including 70 men (55%) with an estimated glomerular filtration rate (eGFR) of 39 ± 30 mL/min/1.73 m2. Lower pRNFL thickness was found to be related to high-sensitivity troponin I (r = -0.362, p < 0.001) and total coronary calcification (r = -0.194, p = 0.032). In a multivariate analysis, pRNFL measurements remained associated with age (ß = -0.189; -0.739--0.027; p = 0.035) and high-sensitivity troponin I (ß = -0.301; -0.259--0.071; p < 0.001). Severe coronary calcification (Agatston score ≥ 400 HU) was related to a worse eGFR (p = 0.008), a higher grade of CKD (p = 0.036), and a thinner pRNFL (p = 0.011). The ROC curve confirmed that the pRNFL measurement could determine the patients with an Agatston score of ≥400 HU (AUC 0.638; 95% CI 0.525-0.750; p = 0.015). Our study concludes that measurement of pRNFL thickness using OCT is related to the markers associated with ischemic heart disease, such as coronary calcification and high-sensitivity troponin I, in the CKD population.

AI-driven remote sensing enhances Mediterranean seagrass monitoring and conservation to combat climate change and anthropogenic impacts.

Seagrasses are undergoing widespread loss due to anthropogenic pressure and climate change. Since 1960, the Mediterranean seascape lost 13-50% of the areal extent of its dominant and endemic seagrass-Posidonia oceanica, which regulates its ecosystem. Many conservation and restoration projects failed due to poor site selection and lack of long-term monitoring. Here, we present a fast and efficient operational approach based on a deep-learning artificial intelligence model using Sentinel-2 data to map the spatial extent of the meadows, enabling short and long-term monitoring, and identifying the impacts of natural and human-induced stressors and changes at different timescales. We apply ACOLITE atmospheric correction to the satellite data and use the output to train the model along with the ancillary data and therefore, map the extent of the meadows. We apply noise-removing filters to enhance the map quality. We obtain 74-92% of overall accuracy, 72-91% of user's accuracy, and 81-92% of producer's accuracy, where high accuracies are observed at 0-25 m depth. Our model is easily adaptable to other regions and can produce maps in in-situ data-scarce regions, providing a first-hand overview. Our approach can be a support to the Mediterranean Posidonia Network, which brings together different stakeholders such as authorities, scientists, international environmental organizations, professionals including yachting agents and marinas from the Mediterranean countries to protect all P. oceanica meadows in the Mediterranean Sea by 2030 and increase each country's capability to protect these meadows by providing accurate and up-to-date maps to prevent its future degradation.

Extending the Scope of the C-Functionalization of Cyclam via Copper(I)-Catalyzed Alkyne-Azide Cycloaddition to Bifunctional Chelators of Interest.

Cyclam, known for its potent chelation properties, is explored for diverse applications through selective N-functionalization, offering versatile ligands for catalysis, medical research, and materials science. The challenges arising from N-alkylation, which could decrease the coordination properties, are addressed by introducing a robust C-functionalization method. The facile two-step synthesis proposed here involves the click chemistry-based C-functionalization of a hydroxyethyl cyclam derivative using Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC). Boc-protecting groups prevent undesired copper coordination, resulting in compounds with a wide range of functionalities. The optimized synthesis conditions enable C-functional cyclams to be obtained easily and advantageously, with high application potential in the previously cited fields. The methodology has been extended to trehalose-based Siamese twin amphiphiles, enabling efficient gene delivery applications.

Toxic-Induced Encephalopathy Following Chemsex in a Young HIV-Positive Male: A Complex Case of Acute Cognitive Impairment with Anterograde Amnesia and Behavioral Alterations.

BACKGROUND: A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the 'chemsex' context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization. CLINICAL FINDING: After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3 mg/dl - elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3 weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1. CONCLUSIONS: The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.

Trehalose-polyamine/DNA nanocomplexes: impact of vector architecture on cell and organ transfection selectivity.

A novel family of precision-engineered gene vectors with well-defined structures built on trehalose and trehalose-based macrocycles (cyclotrehalans) comprising linear or cyclic polyamine heads have been synthesized through procedures that exploit click chemistry reactions. The strategy was conceived to enable systematic structural variations and, at the same time, ensuring that enantiomerically pure vectors are obtained. Notably, changes in the molecular architecture translated into topological differences at the nanoscale upon co-assembly with plasmid DNA, especially regarding the presence of regions with short- or long-range internal order as observed by TEM. In vitro and in vivo experiments further evidenced a significant impact on cell and organ transfection selectivity. Altogether, the results highlight the potential of trehalose-polyamine/pDNA nanocomplex monoformulations to achieve targeting transfection without the need for any additional cell- or organ-sorting component.

Methodology for Calculating the Damaged Surface and Its Relationship with Power Loss in Photovoltaic Modules by Electroluminescence Inspection for Corrective Maintenance.

Photovoltaic panels are exposed to various external factors that can cause damage, with the formation of cracks in the photovoltaic cells being one of the most recurrent issues affecting their production capacity. Electroluminescence (EL) tests are employed to detect these cracks. In this study, a methodology developed according to the IEC TS 60904-13 standard is presented, allowing for the calculation of the percentage of type C cracks in a PV panel and subsequently estimating the associated power loss. To validate the methodology, it was applied to a polycrystalline silicon module subjected to incremental damage through multiple impacts on its rear surface. After each impact, electroluminescence images and I-V curves were obtained and used to verify power loss estimates. More accurate estimates were achieved by assessing cracks at the PV cell level rather than by substring or considering the entire module. In this context, cell-level analysis becomes indispensable, as the most damaged cell significantly influences the performance of the photovoltaic model. Subsequently, the developed methodology was applied to evaluate the conditions of four photovoltaic panels that had been in operation, exemplifying its application in maintenance tasks. The results assisted in decision making regarding whether to replace or continue using the panels.

Multiomics plasma effects of switching from triple antiretroviral regimens to dolutegravir plus lamivudine.

INTRODUCTION: The DOLAM trial revealed that switching from triple antiretroviral therapy (three-drug regimen; 3DR) to dolutegravir plus lamivudine (two-drug regimen; 2DR) was virologically non-inferior to continuing 3DR after 48 weeks of follow-up. Weight increased with 2DR relative to 3DR but it did not impact on metabolic parameters. METHODS: Multiomics plasma profile was performed to gain further insight into whether this therapy switch might affect specific biological pathways. DOLAM (EudraCT 201500027435) is a Phase 4, randomized, open-label, non-inferiority trial in which virologically suppressed persons with HIV treated with 3DR were assigned (1:1) to switch to 2DR or to continue 3DR for 48 weeks. Untargeted proteomics, metabolomics and lipidomics analyses were performed at baseline and at 48 weeks. Univariate and multivariate analyses were performed to identify changes in key molecules between both therapy arms. RESULTS: Switching from 3DR to 2DR showed a multiomic impact on circulating plasma concentration of N-acetylmuramoyl-L-alanine amidase (Q96PD5), insulin-like growth factor-binding protein 3 (A6XND0), alanine and triglyceride (TG) (48:0). Correlation analyses identified an association among the up-regulation of these four molecules in persons treated with 2DR. CONCLUSIONS: Untargeted multiomics profiling studies identified molecular changes potentially associated with inflammation immune pathways, and with lipid and glucose metabolism. Although these changes could be associated with potential metabolic or cardiovascular consequences, their clinical significance remains uncertain. Further work is needed to confirm these findings and to assess their long-term clinical consequences.

Pandemic Grief and Suicidal Ideation in Latin American Countries: A Network Analysis.

This study aimed to characterize the network structure of pandemic grief symptoms and suicidal ideation in 2174 people from eight Latin American countries. Pandemic grief and suicidal ideation were measured using the Pandemic Grief Scale and a single item, respectively. Network analysis provides an in-depth characterization of symptom-symptom interactions within mental disorders. The results indicated that, "desire to die," "apathy" and "absence of sense of life" are the most central symptoms in a pandemic grief symptom network; therefore, these symptoms could be focal elements for preventive and treatment efforts. Suicidal ideation, the wish to die, and the absence of meaning in life had the strongest relationship. In general, the network structure did not differ among the participating countries. It identifies specific symptoms within the network that may increase the likelihood of their co-occurrence and is useful at the therapeutic level.

Falta de adherencia a ticagrelor frente a clopidogrel y riesgo de eventos en pacientes con SCA. Resultados del registro CREA-ARIAM / Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry

Introduction and objectives Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). Methods We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. Results Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,−0.99-1.24). Conclusions In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor (AU)

Introducción y objetivos Una baja adherencia al tratamiento antiagregante plaquetario doble (TAPD) condiciona peor pronóstico tras un síndrome coronario agudo (SCA). Se analizó si el riesgo de eventos adversos cardiovasculares mayores (MACE) tras la interrupción prematura del TAPD varía según el inhibidor del P2Y12. Métodos Análisis preespecificado de pacientes con SCA tratados con ticagrelor o clopidogrel entre 2015 y 2019 dentro de un registro prospectivo multicéntrico. Se categorizó la suspensión prematura como indicada por el médico o como interrupción por hemorragia, efectos secundarios o incumplimiento del paciente. La asociación entre la suspensión del TAPD y los MACE se analizó mediante modelos multivariantes de Cox dependientes del tiempo, con estimadores robustos ponderados por probabilidad inversa de censura. Resultados De 2.180 pacientes, 174 (8,3%) suspendieron el TAPD precozmente (126 por indicación médica y 48 por disrupción). Los pacientes incumplidores tenían más edad y más comorbilidad que los adherentes. Frente a la suspensión indicada por el médico, la disrupción del TAPD fue más precoz y frecuente con el ticagrelor que con el clopidogrel. La suspensión del TAPD condicionó mayor riesgo de MACE (HRajustada=1,32; IC95%, 1,10-1,76), principalmente en caso de la disrupción (HRajustada=1,47; IC95%, 1,22-1,73). Este riesgo aumentó exponencialmente en los 90 días posteriores al SCA y fue más evidente con ticagrelor (pinteracción<0,001). Tras considerar la duración del TAPD, esta interacción no resultó significativa en la escala aditiva (exceso de riesgo debido a interacción=0,12; IC95%, –0,99 a 1,24)(AU)

Insights into the spatial ecology of severely injured free-living felids: Iberian lynx, bobcat, and snow leopard.

Severe musculoskeletal diseases, such as those associated with congenital or traumatic events, that result in missing limbs may compromise the fitness and survival of free-living felids. Here we report the space use of four amputee individuals from three felid species captured from 2017 to 2022 in Missouri (USA), Toledo and Badajoz (Spain), and Suitai Khairkhan Mountain (Mongolia). We describe home ranges and daily travel distances post-release of free-living felids that had either suffered a traumatic amputation or following a surgical amputation. We compared these data with those reported in the literature for felids without amputations. Forelimb or hindlimb amputation did not affect the hunting, mating, or territory patrolling behavior of any of the individuals. However, we recorded significant differences in the daily movement before and after the traumatic event of the Iberian lynx forelimb amputee. We attribute this difference to the physical impairment, although we consider other variables that may have played a role. Nevertheless, all animals appeared to cope well with their limb loss, showing home ranges and daily distances within those recorded for their sex and species. Unless amputee felids represent a threat to domestic livestock or humans, our data suggest these individuals may remain free-living as they contribute to local population persistence and appear to maintain good general health and welfare.

Role of maraviroc and/or rapamycin in the liver of IL10 KO mice with frailty syndrome.

Cellular senescence and low-grade inflammation favor the acceleration of aging. The liver is an essential metabolic organ because changes related to its function are related to age-related diseases. The objective of this study was to evaluate the effects of maraviroc (MVC) and/or rapamycin (RAPA) on liver tissue in an experimental model of frailty syndrome in mice, since MVC and RAPA are two molecules able to decrease CCR5 expression, which is overexpressed in patients with frailty. Methods: Eighty male homozygous IL10KO mice were randomly assigned to one of 4 groups (n = 20): i) IL10KO group; ii) MVC group, iii) RAPA group, and iv) MVC-RAPA group. Liver samples were analyzed. Gene expression quantification and western blotting were also performed. The proinflammatory cytokines IL-6 and IL-18 were decreased in MVC and MVC/RAPA groups, IL-12 was decreased in RAPA and MVC/RAPA groups and TNF-α was decreased in all therapeutic groups. P21 was decreased in RAPA and MVC/RAPA groups, Galactosidase beta-1, was also significantly reduced in all therapeutic groups, as were NF-kB1, NF-kB2 and STAT3. In all groups, mTOR and CCL5 were significantly reduced. CCR5 expression was decreased in the MVC and MVC/RAPA groups. Conclusion: MVC and RAPA may protect against some factors involved in liver aging. More studies will be necessary to verify their clinical applications.

Analysis of the culturable gut yeast microbiota of dogs with digestive disorders.

Despite the increasing interest in studying the gut mycobiota of dogs, the association between fungal colonization and the development of digestive disorders in this species remains largely understudied. On the other hand, the high prevalence of antifungal-resistant yeasts detected in previous studies in samples from animals represents a major threat to public health. We analyzed the presence of culturable yeasts in 112 rectal swab samples obtained from dogs with digestive disorders attended in a veterinary teaching hospital. Our results revealed that Malassezia pachydermatis was frequently isolated from the studied dog population (33.9% of samples), and that the isolation of this yeast was significantly associated to the age of animals, but not to their sex, disease group, or the presence of vomits and/or diarrhea. In contrast, other yeast species were less prevalent (17.9% of samples in total), and their isolation was not significantly associated to any variable included in the analysis. Additionally, we observed that 97.5% of the studied M. pachydermatis isolates (n = 158, 1-6 per positive episode) displayed a minimum inhibitory concentration (MIC) value >4 µg/ml to nystatin, 31.6% had a MIC ≥32 µg/ml to fluconazole, and 27.2% had a MIC >4 µg/ml to amphotericin B. The antifungal susceptibility profiles of non-Malassezia (n = 43, 1-7 per episode) were more variable and included elevated MIC values for some antifungal-species combinations. These results confirm that the intestine of dogs is a reservoir of opportunistic pathogenic yeasts and suggest that the prevalence of M. pachydermatis colonization depends more on the age of animals than on any specific digestive disorder.

Mpox in people with past infection or a complete vaccination course: a global case series.

BACKGROUND: Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017-18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve the understanding of this disease in the setting of previous immunity. METHODS: In this global case series, international collaborators from nine countries provided data on individuals with PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were descriptive. FINDINGS: We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection and infection after vaccination. The median age of individuals was 36 years (IQR 30-45; range 21-58). Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a necrotising neck lesion. INTERPRETATION: The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other published cohorts during the 2022 outbreak-predominantly young, sexually active gay and bisexual men who have sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series both disease duration and severity appear to be reduced. FUNDING: None.

Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry.

INTRODUCTION AND OBJECTIVES: Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). METHODS: We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. RESULTS: Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,-0.99-1.24). CONCLUSIONS: In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor. Clinical trial registered at ClinicalTrials.gov (Identifier: NCT02500290).

Life expectancy of people with HIV on antiretroviral therapy in Spain.

OBJECTIVE: To estimate life expectancy of people with HIV (PWH) and describe causes of death. DESIGN: Antiretroviral therapy (ART)-naive adults from the CoRIS cohort starting ART in 2004-2019. METHODS: We calculated life expectancy at age 40 for men and women according to their ART initiation period, and stratified by transmission category, CD4 + cell count and AIDS diagnosis. We estimated life expectancy in 10-year age bands using life tables constructed from mortality rates, estimated through Poisson models. RESULTS: Life expectancy increased from 65.8 [95% confidence interval (CI) 65.0-66.6] in 2004-2008 to 72.9 (72.2-73.7) in 2014-2019 in men [general population comparators (GPC): 79.1 and 81.2 years, respectively] and from 65.8 (65.0-66.6) to 72.5 (71.8-73.3) in women (GPC: 84.9 and 86.4, respectively). Non-AIDS-related deaths accounted for 68% of deaths among men and 78% among women. Life expectancy was longer when starting ART with higher CD4 + cell counts and without AIDS. For men acquiring HIV through sex with men, starting ART in 2014-2019 without AIDS, life expectancy was 75.0 (74.2-75.7) with CD4 + cell count less than 200 cells/µl, rising to 78.1 (77.5-78.8) with CD4 + cell count at least 350 cells/µl. Corresponding figures were 70.1 (69.4-70.9) and 76.0 (75.3-76.7) for men acquiring HIV heterosexually (HTX) and 61.5 (60.7-62.3) and 69.0 (68.2-69.8) for those acquiring HIV through injection drug use (IDU). For women starting ART from 2014 without AIDS, life expectancy increased from 71.7 (71.0-72.4) to 77.3 (76.7-77.9) among HTX and from 63.7 (62.9-64.5) to 70.7 (70.0-71.5) among IDU. CONCLUSION: Our findings confirm the progressive improvement of life expectancy in PWH in Spain over the last decades, supporting the insurability of PWH on suppressive ART in our current setting and time.