Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, ...reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 μg/ml for C. dubliniensis and 2, 8, 2, and 16 μg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.
The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within ...clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.
Objective
To describe clinical effectiveness of belimumab for systemic lupus erythematosus (SLE) in real-world practice in Argentina.
Methods
This retrospective, observational study analysed medical ...record data of patients with SLE treated with belimumab in 15 centres in Argentina. Primary endpoint: overall clinical response (assessed on a scale similar to the 6-point Physician Global Assessment) at months 6, 12, 18 and 24, all versus index (belimumab initiation). Secondary endpoints: improvement in disease activity (SELENA-SLEDAI), SLE manifestations, and corticosteroid dose change.
Results
Records for 81 patients (91% female) were analysed. Clinical improvements were reported for 95%, 95%, 98% and 100% patients at 6, 12, 18, and 24 months post index, respectively. Mean SELENA-SLEDAI score decreased from 11.21 at index to 4.76, 3.77, 3.86 and 2.17 at 6, 12, 18, and 24 months post index, respectively. Number of flares decreased from 1.05 at index to 0.21, 0.09, 0.22 and 0.30 at 6, 12, 18, and 24 months post index, respectively. Mean corticosteroid dose was 14.59 mg/day at index, and 6.45, 5.18, 5.17 and 4.78 mg/day at 6, 12, 18, and 24 months post index, respectively.
Conclusions
Real-world patients with SLE treated with belimumab in Argentina demonstrated clinical improvements and reductions in corticosteroid dose.
Summary
We report the largest study on the prevalence and distribution of HCV genotypes in Spain (2000‐2015), and we relate them with clinical, epidemiological and virological factors. Patients from ...29 hospitals in 10 autonomous communities (Andalusia, Aragon, Castilla‐Leon, Catalonia, Galicia, Canary Islands, Madrid Community, Valencian Community, Murcia Region and Basque Country) have been studied. Annual distribution of HCV genotypes and subtypes, as well as gender, age, transmission route, HIV and/or HBV coinfection, and treatment details were recorded. We included 48595 chronically HCV‐infected patients with the following characteristics: median age 51 years (IQR, 44‐58), 67.9% male, 19.1% HIV‐coinfected, 23.5% HBV‐coinfected. Parenteral transmission route was the most frequent (58.7%). Genotype distribution was 66.9% GT1 (24.9% subtype 1a and 37.9% subtype 1b), 2.8% GT2, 17.3% GT3, 11.4% GT4 and 0.1% GT5 and 0.02% GT6. LiPA was the most widely HCV genotyping test used (52.4%). HCV subtype 1a and genotypes 3 and 4 were closely associated with male gender, parenteral route of infection and HIV and HBV coinfection; in contrast, subtype 1b and genotype 2 were associated with female gender, nonparenteral route and mono‐infection. Age was related to genotype distribution, and different patterns of distribution and biodiversity index were observed between different geographical areas. Finally, we describe how treatment and changes in transmission routes may have affected HCV genotype prevalence and distribution patterns. We present the most recent data on molecular epidemiology of hepatitis C virus in Spain. This study confirms that genotype distributions vary with age, sex, HIV and HBV coinfection and within geographical areas and epidemiological groups.
Abstract Parkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms ...underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET (18 F-DOPA Ki and11 C-DTBZ binding potential), as well as with TH-immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features.
Caregiving can be a stressful task with severe consequences on caregivers' health. Our aim was to evaluate the profile and the burden of caregivers of patients with home artificial nutrition (HAN) in ...our area.
We conducted a prospective observational study of patients who had started HAN over a period of a year (n=573) and their home caregivers (n=103). Epidemiological characteristics of the patients and the type of HAN were registered. Caregivers' profile data (gender, age and degree of kinship) and Zarit Burden Assessments were recorded.
Care recipients had a median age of 79.0 (IQR 87) years, neurological and oncological diseases in 50% and a high rate of mobility limitations (80%). Oral supplements with high-calorie formulas were predominant (60%). The usual caregiver profile was a patient's daughter with a mean age of 53.1 (s.d. 13.4) years acting as the primary caregiver. Burden was absent in 49.5%, light in 18.4% and intense in 32% of caregivers. Intense burden was more frequent in oral over enteral nutrition (42% versus 22.6%; P=0.036). Supplementary nutrition was also associated with higher caregiver burden scores compared with complete diets. In patients with functional limitations, a tendency toward a slightly higher burden was observed. No differences in caregiver burden were detected according to other patient or caregiver characteristics.
HAN type appears to be a factor influencing caregiver burden and therefore, evaluation of caregiver burden should be part of HAN programs.
Summary
Background
Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines are poorly characterized.
Objective
To describe and classify cutaneous reactions ...after SARS‐CoV‐2 vaccination.
Methods
A nationwide Spanish cross‐sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face‐to‐face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification.
Results
From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer‐BioNTech; 40·2%), mRNA‐1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site (‘COVID arm’, 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea‐like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA‐1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer‐BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA‐1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment.
Conclusions
Cutaneous reactions after SARS‐CoV‐2 vaccination are heterogeneous. Most are mild‐to‐moderate and self‐limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.
What is already known about this topic?
In clinical trials, COVID‐19 vaccines were associated with cutaneous adverse events, especially local injection site reactions.
Previous descriptions of cutaneous reactions beyond the injection site were case reports or mostly reported by non‐dermatologists and lacked clinical images.
What does this study add?
We describe and classify a large, representative sample of patients with unexplained skin manifestations after COVID‐19 vaccination, using consensus to define associated morphological patterns.
We describe six morphological reaction patterns and herpesvirus reactivations, and their association with demographic factors and the medical record, and provide illustrations to allow for easy recognition.
Linked Comment: V. Bataille and S. Puig. Br J Dermatol 2022; 186:15.
Plain language summary available online
Space Systems have been historically characterised by high performance, high reliability and high cost. Every new generation of space systems tends to improve performance, keep as much as possible ...reliability, speeding the lead time and lower the cost. Aggressive approach is nowadays followed by some of the players of the new space ecosystem where, for instance, reliability can be relaxed thanks for the in-orbit redundancy or robustness to failures by having a constellation with a high number of satellites. This push towards the technology and system limit requires to investigate new methods for the manufacturing of RF/Microwave parts. RF devices such as those based on waveguide structures, benefit from an additive manufacturing approach in terms of radio frequency (RF) performance and compactness. However each manufacturing approach comes with specific features and limitations which need to be well understood and, in some cases, even taking advantage of them. This paper provides a short review of some of the RF/Microwave parts already manufactured using this technology. The paper will focus mainly on metal 3D printing parts since this technology is, at the moment, well accepted by the space community.