Background
The impact of coronavirus disease 2019 (COVID‐19) in haematological patients (HP) has not been comprehensively reported.
Methods
We analysed 39 patients with SARS‐CoV‐2 infection and ...haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non‐cancer patients with COVID‐19. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome.
Results
The most frequent haematological diseases were lymphoma (30%) and multiple myeloma (30%). Eighty‐seven % HP developed moderate or severe disease. Patients with haematological malignancies had a significantly higher mortality rate compared to non‐cancer patients (35.9% vs 13.2%; P = .003 (odds ratio 6.652). The worst outcome was observed in chronic lymphocytic leukaemia patients. Only age >70 years and C reactive protein >10 mg/dl at admission were associated with higher risk of death (odds ratio 34.86, P = .003 and 13.56,P = .03). Persistent viral sheddind was detected in 5 HP. Active chemotherapy, viral load at diagnosis and COVID‐19 therapy were not predictors of outcome.
Conclusion
Mortality of COVID‐19 is significantly higher in patients with haematological malignancies compared to non‐cancer patients. The impact of persistent viral shedding must be considered in order to re‐start therapies and maintain infectious control measures.
In cases of treatment failure in acute myeloid leukemia (AML), the utility of mutational profiling in primary refractoriness and relapse is not established. We undertook a perspective study using ...next-generation sequencing (NGS) of clinical follow-up samples (n=91) from 23 patients with AML with therapeutic failure to cytarabine plus idarubicin or fludarabine. Cases of primary refractoriness to treatment were associated with a lower number of DNA variants at diagnosis than cases of relapse (median 1.67 and 3.21, respectively, p=0.029). The most frequently affected pathways in patients with primary refractoriness were signaling, transcription and tumor suppression, whereas methylation and splicing pathways were mainly implicated in relapsed patients. New therapeutic targets, either by an approved drug or within clinical trials, were not identified in any of the cases of refractoriness (0/10); however, 8 potential new targets were found in 5 relapsed patients (5/13) (p=0.027): 1 IDH2, 3 SF3B1, 2 KRAS, 1 KIT and 1 JAK2. Sixty-five percent of all variants detected at diagnosis were not detected at complete response (CR). Specifically, 100% of variants in EZH2, RUNX1, VHL, FLT3, ETV6, U2AF1, PHF6 and SF3B1 disappeared at CR, indicating their potential use as markers to evaluate minimal residual disease (MRD) for follow-up of AML. Molecular follow-up using a custom NGS myeloid panel of 32 genes in the post-treatment evaluation of AML can help in the stratification of prognostic risk, the selection of MRD markers to monitor the response to treatment and guide post-remission strategies targeting AML, and the selection of new drugs for leukemia relapse.
Purpose
To evaluate the impact of trabecular micro bypass stents (iStent Inject) on refractive outcomes with toric intraocular lens (IOL) in glaucomatous eyes.
Methods
We identified glaucomatous eyes ...receiving a toric IOL between October 2017 and December 2020. Eyes with iStent implantation were included in the study group and eyes undergoing isolated phacoemulsification served as controls. Corrected and uncorrected visual acuity, manifest refraction, intraocular pressure (IOP), and number of hypotensive drugs three months after surgery were evaluated.
Results
26 eyes comprised the study group and 41 eyes the control group. Mean postoperative refractive cylinder was 0.26D in the control and 0.11D in the iStent group, with 63% and 85% of eyes with a cylinder of 0 and 85% and 92% of eyes with a cylinder ≤ 0.5D respectively. The mean absolute difference between target and outcome spherical equivalent was 0.26D in the control and 0.22D in the iStent group, with all eyes within 0.75D of target. LogMar uncorrected postoperative vision in eyes targeted for emmetropia was 0.04 in the control and 0.03 in the iStent group. There was a statistically significant reduction in IOP and number of hypotensive drugs in both groups, with a mean decrease in IOP of 8.6% in the control and 15.7% in the iStent group. The number of hypotensive drugs dropped from 1.63 ± 0.80 to 1.34 ± 0.91 in the control group and from 2.12 ± 0.65 to 0.44 ± 0.71 in the iStent group.
Conclusion
Toric IOLs provide predictable refractive outcomes in glaucomatous eyes undergoing combined phacoemulsification with iStent implantation, reducing postoperative spectacle dependence.
The omicron (B.1.1.529) variant of SARS-CoV-2 has increased capacity to elude immunity and cause breakthrough infections. The aim of this study was to estimate the effectiveness of mRNA-based vaccine ...boosters (third dose) against infection with the omicron variant by age, sex, time since complete vaccination, type of primary vaccine, and type of booster.
In this nationwide cohort study, we linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) to select community-dwelling individuals aged 40 years or older, who completed their primary vaccine schedule at least 3 months before the start of follow-up, and had not tested positive for SARS-CoV-2 since the start of the pandemic. On each day between Jan 3, and Feb 6, 2022, we matched individuals who received a booster mRNA vaccine and controls of the same sex, age group, postal code, type of vaccine, time since primary vaccination, and number of previous tests. We estimated risk of laboratory-confirmed SARS-CoV-2 infection using the Kaplan-Meier method and compared groups using risk ratios (RR) and risk differences. Vaccine effectiveness was calculated as one minus RR.
Between Jan 3, and Feb 6, 2022, 3 111 159 matched pairs were included in our study. Overall, the estimated effectiveness from day 7 to 34 after a booster was 51·3% (95% CI 50·2–52·4). Estimated effectiveness was 52·5% (51·3–53·7) for an mRNA-1273 booster and 46·2% (43·5–48·7) for a BNT162b2 booster. Effectiveness was 58·6% (55·5–61·6) if primary vaccination had been with ChAdOx1 nCoV-19 (Oxford–AstraZeneca), 55·3% (52·3–58·2) with mRNA-1273 (Moderna), 49·7% (48·3–51·1) with BNT162b2 (Pfizer–BioNTech), and 48·0% (42·5–53·7) with Ad26.COV2.S (Janssen). Estimated effectiveness was 43·6% (40·0–47·1) when the booster was administered between 151 days and 180 days after complete vaccination and 52·2% (51·0–53·3) if administered more than 180 days after primary scheduled completion.
Booster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster.
None.
CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores ...the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations.
Eleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death.
After a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression.
This is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results.
Background
Lack of specific protocols for neonatal donation contributes to the rarity of neonatal donors. In this study, we evaluate the impact of the implementation of a neonatal donation protocol ...in our NICU.
Methods
In this single‐center study, we conducted a retrospective chart review of neonatal deaths in our NICU from January 2013 to January 2022. The study was divided into two periods: before and after the implementation of a neonatal donation protocol. The referral rates of potential neonatal donors to the OPO in the two periods were compared using the chi‐square test. A p value < .05 was considered statistically significant.
Results
Sixty‐four infants were reviewed. Seven (10.9%) met the inclusion criteria for potential neonatal donors after DCC. The referral rate of potential neonatal donors increased from 2.5% to 16.7% after the implementation of this protocol (p = .041), and one infant (4.1%) became an effective heart‐valve donor.
Conclusion
The implementation of a local neonatal donation protocol could have contributed to increase the referral rate of potential neonatal donors in our NICU. Following the implementation of a local neonatal donation protocol, we were able to perform a heart‐valve donation for the first time in our unit.
The right to die is an international dilemma. Some countries and states already have laws regulating one of the most common applications of this right, the active voluntary euthanasia. The evidence ...from these countries highlights the importance of a bioethical framework to limit some of its applications. In this regard, the evaluation of attitudes towards euthanasia in medical personnel will allow to understand the attitudes of these professionals and how they can deal with such requests, whether this assisted death is decided by the patients or their surroundings. Consequently, the aim of this study was to develop a brief scale to evaluate attitudes, as well as to determine their significance according to the gender and seniority of the professionals in this situation. A double design strategy was followed. On the one hand, a psychometric design with an exploratory and confirmatory factor analysis and, on the other, a descriptive analytical design for the comparison of groups. A six-item scale (AE-PM) and two factors were extracted. The first focuses on attitudes towards euthanasia to alleviate suffering for medical reasons and the second one to alleviate the patient’s emotional suffering. The scale (AHE-PM) is useful for the rapid exploration of attitudes towards euthanasia in physicians, a professional group with limited free time, who may also encounter relatively frequent requests for active voluntary euthanasia. The two factors obtained allow attitudes to be assessed from a bioethical perspective, providing information on the application under apparent medical justification and in situations based on the patient’s subjective emotional suffering.
Rare cancers epidemiology is better known compared to the other rare diseases. Thanks to the long history of the European population-based cancer registries and to the EUROCARE huge database, the ...burden of rare cancers has been estimated the European (EU28) population. A considerable fraction of all cancers is represented by rare cancers (24%). They are a heterogeneous group of diseases, but they share similar problems: uncertainty of diagnosis, lack of therapies, poor research opportunities, difficulties in clinical trials, lack of expertise and of centres of reference. This paper analyses the major epidemiological indicators of frequency (incidence and prevalence) and outcome (5-year survival) of all rare cancers combined and of selected rare cancers that will be in depth treated in this monographic issue. Source of the results is the RARECAREnet search tool, a database publicly available. Disparities both in incidence and survival, and consequently in prevalence of rare cancers were reported across European countries. Major differences were shown in outcome: 5-year relative survival for all rare cancers together, adjusted by age and case-mix, varied from 55% or more (Italy, Germany, Belgium and Iceland) and less than 40% (Bulgaria, Lithuania and Slovakia). Similarly, for all the analyzed rare cancers, a large survival gap was observed between the Eastern and the Nordic and Central European regions. Dramatic geographical variations were assessed for curable cancers like testicular and non epithelial ovarian cancers. Geographical difference in the annual age-adjusted incidence rates for all rare cancers together varied between >140 per 100,000 (Italy, Scotland, France, Germany, and Switzerland) and <100 (Finland, Portugal, Malta, and Poland). Prevalence, the major indicator of public health resources needs, was about 7–8 times larger than incidence. Most of rare cancers require complex surgical treatment, thus a multidisciplinary approach is essential and treatment should be provided in centres of expertise and/or in networks including expert centres. Networking is the most appropriate answer to the issues pertaining to rare cancers. Actually, in Europe, an opportunity to improve outcome and reduce disparities is provided by the creation of the European Reference Networks for rare diseases (ERNs). The Joint Action of rare cancers (JARC) is a major European initiative aimed to support the mission of the ERNs. The role of population based cancer registries still remains crucial to describe rare cancers management and outcome in the real word and to evaluate progresses made at the country and at the European level.
Abstract
Objectives
To describe current resistance to the β-lactams empirically recommended in the guidelines in bloodstream infection (BSI) episodes caused by Gram-negative bacilli (GNB).
Methods
...Retrospective, multicentre cohort study of the last 50 BSI episodes in haematological patients across 14 university hospitals in Spain. Rates of inappropriate empirical antibiotic therapy (IEAT) and impact on mortality were evaluated.
Results
Of the 700 BSI episodes, 308 (44%) were caused by GNB, mainly Escherichia coli (141; 20.1%), Klebsiella spp. (56; 8%) and Pseudomonas aeruginosa (48; 6.9%). Among GNB BSI episodes, 80 (26%) were caused by MDR isolates. In those caused by Enterobacterales, 25.8% were ESBL producers and 3.5% were carbapenemase producers. Among P. aeruginosa BSI episodes, 18.8% were caused by MDR isolates. Overall, 34.7% of the isolated GNB were resistant to at least one of the three β-lactams recommended in febrile neutropenia guidelines (cefepime, piperacillin/tazobactam and meropenem). Despite extensive compliance with guideline recommendations (91.6%), 16.6% of BSI episodes caused by GNB received IEAT, which was more frequent among MDR GNB isolates (46.3% versus 6.1%; P < 0.001). Thirty day mortality was 14.6%, reaching 21.6% in patients receiving IEAT.
Conclusions
Current resistance to empirical β-lactams recommended in febrile neutropenia guidelines is exceedingly high and IEAT rates are greater than desired. There is an urgent need to adapt guidelines to current epidemiology and better identify patients with a high risk of developing MDR GNB infection.
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