Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 946
Filtrar
1.
Curr Opin Psychol ; 60: 101882, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39278166

RESUMEN

Ego depletion theory proposes that self-regulation depends on a limited energy resource (willpower). The simple initial theory has been refined to emphasize conservation rather than resource exhaustion, extended to encompass decision making, planning, and initiative, and linked to physical bodily energy (glucose). Recent challenges offered alternative explanations (which have largely failed) and questioned replicability (which has now been well established). Methods have improved, particularly with emphasis on longer, stronger manipulations to ensure fatigue. New work extends ego depletion into workplace settings and sports. Interpersonal conflict may be both a major cause and consequence. New questions include the possibility of chronic ego depletion (e.g., in burnout), protective factors and coping strategies, individual differences, and recovery processes.

2.
medRxiv ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39228727

RESUMEN

Objective: Routine use of whole genome sequencing (WGS) has been shown to help identify transmission of pathogens causing healthcare-associated infections (HAIs). However, the current gold standard of short-read, Illumina-based WGS is labor and time-intensive. In light of recent improvements in long-read Oxford Nanopore Technologies (ONT) sequencing, we sought to establish a low resource utilization approach capable of providing accurate WGS-based comparisons of HAI pathogens within a time frame allowing for infection prevention and control (IPC) interventions. Methods: WGS was prospectively performed on antimicrobial-resistant pathogens at increased risk of potential healthcare transmission using the ONT MinION sequencer with R10.4.1 flow cells and Dorado basecalling algorithm. Potential transmission was assessed via Ridom SeqSphere+ for core genome multilocus sequence typing and MINTyper for reference-based core genome single nucleotide polymorphisms using previously published cut-off values. The accuracy of our ONT pipeline was determined relative to Illumina-based WGS data generated from the same genomic DNA sample. Results: Over a six-month period, 242 bacterial isolates from 216 patients were sequenced by a single operator. Compared to the Illumina gold-standard data, our ONT pipeline achieved a Q score of 60 for assembled genomes, even with a coverage rate of as low as 40X. The mean time from initiating DNA extraction to complete genetic analysis was 2 days (IQR 2-3.25 days). We identified five potential transmission clusters comprising 21 isolates (8.7% of all sequenced strains). Combining ONT WGS data with epidemiological data, >70% (15/21) of the isolates originated from patients with potential healthcare transmission links. Conclusions: Via a stand-alone ONT pipeline, we detected potentially transmitted HAI pathogens rapidly and accurately, aligning closely with epidemiological data. Our low-resource method has the potential to assist in the efficient detection and deployment of preventative measures against HAI transmission.

3.
Open Forum Infect Dis ; 11(8): ofae422, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39086466

RESUMEN

Background: Patients with B-cell lymphoma and acute lymphoblastic leukemia (ALL) who receive chimeric antigen receptor T-cell (CAR-T) therapy may experience clinically significant cytomegalovirus infection (CS-CMVi). However, risk factors for CS-CMVi are not well defined. The aims of our study were to identify risk factors for CS-CMVi and the association between CS-CMVi and nonrelapse mortality (NRM) in lymphoma and ALL patients after CAR-T therapy. Methods: We performed a retrospective single-center cohort analysis of CAR-T recipients between January 2018 and February 2021 for treatment of lymphoma and ALL. We collected data on demographics, oncologic history, CAR-T therapy-related complications, and infectious complications within 1 year of therapy. Results: Of 230 patients identified, 22 (10%) had CS-CMVi. At 1 year following CAR-T therapy, 75 patients (33%) developed relapsed disease and 95 (41%) died; NRM at 1 year was 37%. On Cox regression analysis, Asian or Middle Eastern race (adjusted hazard ratio [aHR], 13.71 [95% confidence interval {CI}, 5.41-34.74]), treatment of cytokine release syndrome/immune effector cell-associated neurotoxicity syndrome with steroids (aHR, 6.25 [95% CI, 1.82-21.47]), lactate dehydrogenase at time of CAR-T therapy (aHR, 1.09 [95% CI, 1.02-1.16]), and CMV surveillance (aHR, 6.91 [95% CI, 2.77-17.25]) were independently associated with CS-CMVi. CS-CMVi was independently associated with NRM at 1 year after CAR-T therapy (odds ratio, 2.49 [95% CI, 1.29-4.82]). Conclusions: Further studies of immunologic correlatives and clinical trials to determine the efficacy of prophylactic strategies are needed to understand the role of CS-CMVi and post-CAR-T mortality.

4.
Open Forum Infect Dis ; 11(8): ofae425, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39091643

RESUMEN

Background: Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit. Methods: We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies. This is a secondary analysis of an expanded cohort that evaluated the clinical utility of plasma mcfDNA sequencing across prespecified and adjudicated outcomes. We examined the percentage of participants for whom plasma mcfDNA sequencing identified a probable cause of pneumonia or clinically relevant nonpneumonia infection. We then assessed potential changes in antimicrobial therapy based on plasma mcfDNA sequencing results and the potential for early mcfDNA testing to avoid bronchoscopy and its associated adverse events. Results: Of 223 participants, at least 1 microbial detection by plasma mcfDNA sequencing was adjudicated as a probable cause of pneumonia in 57 (25.6%) and a clinically relevant nonpneumonia infection in 88 (39.5%). A probable cause of pneumonia was exclusively identified by plasma mcfDNA sequencing in 23 (10.3%) participants. Antimicrobial therapy would have changed for 41 (18.4%) participants had plasma mcfDNA results been available in real time. Among the 57 participants with a probable cause of pneumonia identified by plasma mcfDNA sequencing, bronchoscopy identified no additional probable cause of pneumonia in 52 (91.2%). Conclusions: Plasma mcfDNA sequencing could improve management of both pneumonia and other concurrent infections in immunocompromised patients with suspected pneumonia.

5.
Microorganisms ; 12(8)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39203518

RESUMEN

Vancomycin-resistant enterococci (VRE) commonly colonize the gut of individuals with hematologic malignancies or undergoing hematopoietic cell transplant (HCT) and may cause bacteremia. In 2012, we identified VRE isolates from patients and patients' rooms and showed transmission networks of highly genetically related daptomycin-resistant (DR)-VRE strains. This is a follow-up study performing whole-genome sequencing (WGS) and phylogenetic analyses on 82 clinical VRE strains isolated from stools and blood cultures of patients with leukemia and HCT between 2015 and 2019. Here, we observed transmission of highly genetically related strains between rooms on the same or on different floors, including a DR-VRE strain identified in 2012. Eleven of twenty-eight patients with DR-VRE were never exposed to daptomycin, suggesting horizontal transmission. Fifteen of the twenty-eight patients with DR-VRE died within 30 days of positive blood cultures. Amongst those, one DR-VRE strain belonging to ST1471 had the virulence gene bopD responsible for biofilm formation. Additionally, to our knowledge, this is the first report of a DR-VRE strain belonging to ST323 in the United States. In summary, our study demonstrated the emergence and persistence of VRE strains, especially DR-VRE, in our hospital. Adding WGS to routine infection control measures may timely identify potential horizontal VRE transmission including multi-drug-resistant isolates.

6.
J Clin Med ; 13(16)2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39200962

RESUMEN

Background: Pelvic organ prolapse (POP) affects many women and is often managed with pessary treatment, yet predicting the success of fitting remains challenging. This study aims to identify anatomical parameters associated with successful and unsuccessful pessary treatment using dynamic magnetic resonance imaging (dMRI). Methods: A cross-sectional study in Maastricht University Medical Centre (MUMC+), the Netherlands. Sixteen women with a cystocele and/or descensus uteri minimal POP-Q stage 2, using pessary treatment, were included. All women underwent a dynamic MRI of the pelvic floor at rest, during contraction and on Valsalva. The anatomical parameters evaluated included various lengths and angles. The association between the anatomical parameters and pessary fitted is assessed using partial least squares regression. The predictive accuracy was tested using cross-validation based on the partial least squares model with the most important variables. Results: Seven of the sixteen women (43.8%) were in the non-fitting group (due to movement, rotation or expulsion of the pessary), and nine women (56.3%) were in the fitting group. Participants in the non-fitting group had a significantly lower body mass index (BMI). Variables such as total vaginal length (TVL) and certain angles were highly predictive of pessary fitting success, with variable importance of projection (VIP) scores indicating their importance. The prediction models showed accuracies ranging from 53.3% to 80.0%. Conclusions: In this explorative study, TVL, cervical length (CL), sacrococcygeal angle and pubococcygeal angle were key variables associated with pessary fitting success. These findings offer valuable insights for optimizing pessary fitting procedures and the development of new pessaries.

7.
Gynecol Oncol ; 188: 169-183, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38970844

RESUMEN

BACKGROUND: Evidence on the optimal follow-up schedule after endometrial cancer is lacking. The study aim was to compare satisfaction with care between women who received reduced follow-up care and women who received usual guideline-directed follow-up care for three years after surgery. METHODS: The ENSURE (ENdometrial cancer SURvivors' follow-up carE) trial was a non-inferiority randomized controlled multicenter trial in 42 hospitals in the Netherlands. The intervention arm received reduced follow-up care (4 visits/3 years), while the control group received usual follow-up care (8-11 visits/3 years). Primary outcome was overall satisfaction with care, PSQIII score, over three years follow-up, with a non-inferiority margin of 6. Mixed linear regression, intention-to-treat and per-protocol analyses (presented below) were used. RESULTS: Among 316 women included, overall satisfaction with care was not lower in the reduced follow-up (mean 82; SD = 15) compared with the usual follow-up group (mean 80; SD = 15) group (B = 1.80(-2.09;5.68)). At 6, 12 and 36 months, more women (93/94/90%) in the reduced follow-up group were satisfied with their follow-up schedule than in the usual follow-up group (79/79/82%; p < 0.001; p < 0.001; p = 0.050). CONCLUSIONS AND RELEVANCE: Women with low-risk, early-stage endometrial cancer who received reduced follow-up care were no less satisfied with their care than women receiving usual follow-up care. Compared with usual follow-up, women in the reduced follow-up group had fewer clinical visits and, at the same time, more often reported being satisfied with their follow-up schedule. Findings suggest that reduced follow-up care may be the new standard, but should be tailored to meet additional needs where indicated.


Asunto(s)
Cuidados Posteriores , Neoplasias Endometriales , Satisfacción del Paciente , Humanos , Femenino , Neoplasias Endometriales/terapia , Neoplasias Endometriales/psicología , Persona de Mediana Edad , Anciano , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Países Bajos , Estudios de Seguimiento
8.
Clin Infect Dis ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39041385

RESUMEN

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2017. Since then, there have been major developments, including registration of new antiviral agents. Therefore, the Transplant Associated Virus Infections Forum, which consists of scientists, clinicians, regulators, and industry representatives, has produced an updated version of these definitions that incorporates recent knowledge with the aim of supporting clinical research and drug development. This also includes an update regarding the definition of resistant and refractory CMV infections previously published in 2019. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts among clinicians, scientists, regulators, and industry representatives can provide a platform for this work.

9.
Arch Rehabil Res Clin Transl ; 6(2): 100338, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39006114

RESUMEN

Objective: To determine whether chronic pain persists after complete spinal cord injury (SCI). Design: Prospective observational study regarding the outcome of pre-existent chronic pain of inpatients admitted with new clinically diagnosed complete cervical SCI. For patients who acknowledged chronic pain of ≥3 years duration before the SCI, further questions explored whether they still experienced that pain, whether they were experiencing current posttraumatic pain, and whether they had any past exposure to opioids. The included patients were identified during the initial consultation in the trauma center for treatment of the SCI. Setting: Level I trauma center. Participants: From a total of 49 participants with acute cervical SCI with clinically diagnosed complete motor and sensory tetraplegia admitted between 2018 and 2020, 7 were selected on the basis of a history of chronic pain. Intervention: Collected complete history and performed physical examination with serial follow-ups during the acute hospital stay until death or discharge. Main Outcome Measures: The primary outcome was a finding of chronic pain experienced before new clinical diagnosis of complete SCI, compared with whether or not that pain continued after the SCI injury. The secondary outcome was the relation of persistent pain with opioid use; it was formulated after data collection. Results: Among 49 patients with clinically diagnosed complete cervical SCIs, 7 had experienced prior chronic pain. Four participants experienced a continuation of the prior pain after their complete tetraplegia (4/7), whereas 3 participants did not (3/7). All the participants with continued pain had been previously treated with opioids, whereas those whose pain ceased had not received chronic opioid therapy. Conclusions: There may be a unique form of chronic pain that is based in the brain, irrespective of peripheral pain or spinal mechanisms. Otherwise healthy people with longstanding antecedent chronic pain whose pain persists after acute clinically complete SCI with tetraplegia may provide a new model for evaluation of brain-based pain. Opioids may be requisite for this type of pain.

10.
Oncologist ; 29(9): e1231-e1234, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-38920311

RESUMEN

INTRODUCTION: High-grade serous ovarian cancer (HGSOC) is characterized by high mortality and prevalent recurrences. This study investigates the prognostic value of phosphoglycerate dehydrogenase (PHGDH) in HGSOC which has been linked to metabolic reprogramming and recurrences in other cancers. METHODS: Data from 306 patients with advanced-stage HGSOC treated between 2008 and 2015 were analyzed. PHGDH expression levels were determined using immunohistochemistry and categorized as "low" or "high." RESULTS: PHGDH-high was associated with higher FIGO stage and increased use of neoadjuvant chemotherapy. Patients with PHGDH-high tumors had significantly worse survival than PHDH-low, even after adjusting for confounding factors.


Asunto(s)
Cistadenocarcinoma Seroso , Neoplasias Ováricas , Fosfoglicerato-Deshidrogenasa , Humanos , Femenino , Fosfoglicerato-Deshidrogenasa/metabolismo , Fosfoglicerato-Deshidrogenasa/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/tratamiento farmacológico , Persona de Mediana Edad , Pronóstico , Anciano , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/enzimología , Adulto , Biomarcadores de Tumor/metabolismo , Clasificación del Tumor , Anciano de 80 o más Años
11.
Artículo en Inglés | MEDLINE | ID: mdl-38945270

RESUMEN

BACKGROUND: Herpesviruses represent common and significant infectious complications after allogeneic haematopoietic cell transplantation (HCT). In the last decade, major advances in the prevention and treatment of these infections were accomplished. OBJECTIVES: The aim of this paper is to review the recent advances in the prophylaxis and treatment of herpesvirus infections after allogeneic HCT, to assess the persisting challenges, and to offer future directions for the prevention and management of these infections. SOURCES: We searched PubMed for relevant literature regarding specific herpesviruses complicating allogeneic HCT through March 2024. CONTENT: The largest advances in this past decade were witnessed for cytomegalovirus (CMV) with the advent of letermovir for primary prophylaxis and the development of maribavir as an option for refractory and/or resistant CMV infections in transplant recipients. For varicella zoster virus, prevention of reactivation with the recombinant zoster vaccine offers an additional prophylactic intervention. Pritelivir is being explored for the treatment of drug-resistant or refractory Herpes simplex virus infections. Although rituximab is now an established option for preemptive therapy for Epstein-Barr virus, Human Herpesvirus-6 remains the most elusive virus of the herpesvirus family, with a lack of evidence supporting the benefit of any agent for prophylaxis or for optimal preemptive therapy. IMPLICATIONS: Although considerable advances have been achieved for the treatment and prevention of herpes virus infections, most notably with CMV, the coming years should hold additional opportunities to tame the beast in these herpesviruses postallogeneic HCT, with the advent of new antivirals, cell-mediated immunity testing, and cytotoxic T lymphocytes infusions.

12.
J Behav Ther Exp Psychiatry ; 85: 101963, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38739973

RESUMEN

BACKGROUND AND OBJECTIVES: Sadistic pleasure - gratuitous enjoyment from inflicting pain on others - has devastating interpersonal and societal consequences. The current knowledge on non-sexual, everyday sadism - a trait that resides within the general population - is scarce. The present study therefore focussed on personality correlates of sadistic pleasure. It investigated the relationship between the Dark Triad traits, and both dispositional and state-level sadistic pleasure. METHODS: N = 120 participants filled out questionnaires to assess their level of Dark Triad traits, psychopathy subfactors, and dispositional sadism. Then, participants engaged in an animal-directed task in which they were led to believe that they were killing bugs; and in a human-directed task where they could ostensibly noise blasts another participant. The two behavioral tasks were administered within-subjects, in randomized order. Sadistic pleasure was captured by increases in reported pleasure from pre-to post-task. RESULTS: All Dark Triad traits related to increased dispositional sadism, with psychopathy showing the strongest link. The coldheartedness psychopathy subscale showed a unique combination with both self-reported sadism and increased pleasure following bug grinding. LIMITATIONS: Predominantly female and student sample, limiting generalizability of findings. CONCLUSIONS: Out of all Dark Triad components, psychopathy showed the strongest link with gaining pleasure from hurting others. The results underscore the differential predictive value of psychopathy's subcomponents for sadistic pleasure. Coldheartedness can be considered especially disturbing because of its unique relationship to deriving joy from irreversible harm-infliction (i.e. killing bugs). Our findings further establish psychopathy - and especially its coldheartedness component - as the most adverse Dark Triad trait.


Asunto(s)
Trastorno de Personalidad Antisocial , Placer , Sadismo , Humanos , Masculino , Femenino , Sadismo/fisiopatología , Placer/fisiología , Adulto , Adulto Joven , Trastorno de Personalidad Antisocial/fisiopatología , Adolescente , Personalidad/fisiología , Encuestas y Cuestionarios , Persona de Mediana Edad
13.
Open Forum Infect Dis ; 11(5): ofae235, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38798895

RESUMEN

Background: Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established. Methods: An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: period 1 (before time-out: January 2007-June 2010) and period 2 (after time-out: July 2010-March/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1000 patient-days were also assessed. Results: Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: -0.89 days (95% confidence interval [CI], -1.38 to -.41); linezolid: -0.89 days (95% CI, -1.27 to -.52); meropenem: -0.97 days (95% CI, -1.39 to -.56); tigecycline: -1.41 days (95% CI, -2.19 to -.63); P < .001 for each comparison. Days of therapy/1000 patient-days decreased significantly for meropenem (-43.49; 95% CI, -58.61 to -28.37; P < .001), tigecycline (-35.47; 95% CI, -44.94 to -26.00; P < .001), and daptomycin (-9.47; 95% CI, -15.25 to -3.68; P = .002). Discussion: A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records.

15.
Perspect Psychol Sci ; : 17456916241252085, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38752984

RESUMEN

We identify points of conflict and consensus regarding (a) controversial empirical claims and (b) normative preferences for how controversial scholarship-and scholars-should be treated. In 2021, we conducted qualitative interviews (n = 41) to generate a quantitative survey (N = 470) of U.S. psychology professors' beliefs and values. Professors strongly disagreed on the truth status of 10 candidate taboo conclusions: For each conclusion, some professors reported 100% certainty in its veracity and others 100% certainty in its falsehood. Professors more confident in the truth of the taboo conclusions reported more self-censorship, a pattern that could bias perceived scientific consensus regarding the inaccuracy of controversial conclusions. Almost all professors worried about social sanctions if they were to express their own empirical beliefs. Tenured professors reported as much self-censorship and as much fear of consequences as untenured professors, including fear of getting fired. Most professors opposed suppressing scholarship and punishing peers on the basis of moral concerns about research conclusions and reported contempt for peers who petition to retract papers on moral grounds. Younger, more left-leaning, and female faculty were generally more opposed to controversial scholarship. These results do not resolve empirical or normative disagreements among psychology professors, but they may provide an empirical context for their discussion.

16.
J Clin Med ; 13(5)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38592057

RESUMEN

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.

17.
Clin Microbiol Infect ; 30(6): 803-809, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38460821

RESUMEN

OBJECTIVES: Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. METHODS: We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D-/R-, R+/LTV-, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D-/R- group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. RESULTS: The analysis included 1071 consecutive allo-HCT recipients: 131 D-/R-, 557 R+/LTV-, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D-/R- group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV- and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV-, R+/LTV+, and D-/R- groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12-2.99, p 0.017) for R+/LTV- compared with D-/R- and 1.05 (95% CI 0.62-1.77, p 0.85) for R+/LTV + compared with D-/R-. DISCUSSION: CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.


Asunto(s)
Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Profilaxis Pre-Exposición , Trasplante Homólogo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Acetatos/farmacología , Acetatos/uso terapéutico , Causas de Muerte , Citomegalovirus/aislamiento & purificación , Trasplante de Células Madre Hematopoyéticas/mortalidad , Incidencia , Modelos de Riesgos Proporcionales , Quinazolinas/farmacología , Quinazolinas/uso terapéutico , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo/mortalidad , Resultado del Tratamiento
18.
Virus Evol ; 10(1): vead086, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38361816

RESUMEN

Respiratory syncytial virus (RSV) infection in immunocompromised individuals often leads to prolonged illness, progression to severe lower respiratory tract infection, and even death. How the host immune environment of the hematopoietic stem cell transplant (HCT) adults can affect viral genetic variation during an acute infection is not understood well. In the present study, we performed whole genome sequencing of RSV/A or RSV/B from samples collected longitudinally from HCT adults with normal (<14 days) and delayed (≥14 days) RSV clearance who were enrolled in a ribavirin trial. We determined the inter-host and intra-host genetic variation of RSV and the effect of mutations on putative glycosylation sites. The inter-host variation of RSV is centered in the attachment (G) and fusion (F) glycoprotein genes followed by polymerase (L) and matrix (M) genes. Interestingly, the overall genetic variation was constant between normal and delayed clearance groups for both RSV/A and RSV/B. Intra-host variation primarily occurred in the G gene followed by non-structural protein (NS1) and L genes; however, gain or loss of stop codons and frameshift mutations appeared only in the G gene and only in the delayed viral clearance group. Potential gain or loss of O-linked glycosylation sites in the G gene occurred both in RSV/A and RSV/B isolates. For RSV F gene, loss of N-linked glycosylation site occurred in three RSV/B isolates within an antigenic epitope. Both oral and aerosolized ribavirin did not cause any mutations in the L gene. In summary, prolonged viral shedding and immune deficiency resulted in RSV variation, especially in structural mutations in the G gene, possibly associated with immune evasion. Therefore, sequencing and monitoring of RSV isolates from immunocompromised patients are crucial as they can create escape mutants that can impact the effectiveness of upcoming vaccines and treatments.

19.
J Neurooncol ; 167(1): 99-109, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38351343

RESUMEN

INTRODUCTION: Recent studies have identified that glioblastoma IDH-wildtype consists of different molecular subgroups with distinct prognoses. In order to accurately describe and classify gliomas, the Visually AcceSAble Rembrandt Images (VASARI) system was developed. The goal of this study was to evaluate the VASARI characteristics in molecular subgroups of IDH-wildtype glioblastoma. METHODS: A retrospective analysis of glioblastoma IDH- wildtype with comprehensive next-generation sequencing and pre-operative and post-operative MRI was performed. VASARI characteristics and 205 genes were evaluated. Multiple comparison adjustment by the Bejamin-Hochberg false discovery rate (BH-FDR) was performed. A 1:3 propensity score match (PSM) with a Caliper of 0.2 was done. RESULTS: 178 patients with GBM IDH-WT met the inclusion criteria. 4q12 amplified patients (n = 20) were associated with cyst presence (30% vs. 12%, p = 0.042), decreased hemorrhage (35% vs. 62%, p = 0.028), and non-restricting/mixed (35%/60%) rather than restricting diffusion pattern (5%), meanwhile, 4q12 non-amplified patients had mostly restricting (47.4%) rather than a non-restricting/mixed diffusion pattern (28.4%/23.4%). This remained statistically significant after BH-FDR adjustment (p = 0.002). PSM by 4q12 amplification showed that diffusion characteristics continued to be significantly different. Among RB1-mutant patients, 96% had well-defined enhancing margins vs. 70.6% of RB1-WT (p = 0.018), however, this was not significant after BH-FDR or PSM. CONCLUSIONS: Patients with glioblastoma IDH-wildtype harboring 4q12 amplification rarely have restricting DWI patterns compared to their wildtype counterparts, in which this DWI pattern is present in ~ 50% of patients. This suggests that some phenotypic imaging characteristics can be identified among molecular subtypes of IDH-wildtype glioblastoma.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Estudios Retrospectivos , Glioma/genética , Pronóstico , Isocitrato Deshidrogenasa/genética , Mutación , Ubiquitina-Proteína Ligasas/genética , Proteínas de Unión a Retinoblastoma/genética
20.
J Prev (2022) ; 45(3): 391-403, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38393546

RESUMEN

This research analyzed data from the Youth Asset Study (YAS), a 4-year longitudinal investigation designed to examine the prospective influence of youth assets, which are believed to influence behavior at the individual, family, and community levels, on youth risk behaviors. The purpose was to determine if specific youth assets (e.g., responsible choices, family communication, community involvement) differentially protected adolescents from alcohol, tobacco, and other drug use (ATODU) according to family structure (one-parent and two-parent households). Five waves of data were collected annually over four years from a racially/ethnically diverse sample of adolescents (N = 722, 51.5% male, baseline mean age = 14.1 years). Pearson chi-square tests for independence were used to test for significant differences in the prevalence of assets between one-parent and two-parent households. Generalized linear mixed models were used to identify prospective associations between 17 youth assets and ATODU while stratifying by family structure and controlling for sociodemographic characteristics. Compared to adolescents living in one-parent households, adolescents living in two-parent households were significantly more likely to possess six of 17 assets. Among adolescents living in one-parent households, those who possessed any one of eight youth assets were significantly less likely to use ATODU. Among adolescents living in one-parent households, those with any one of seven assets were significantly less likely to use ATODU. Family- and community-level assets had the most significant asset/ATODU associations for adolescents living in one-parent households (AORs ranged from 0.23 to 0.61). Individual-level assets had the most significant asset/ATODU associations for adolescents living in two-parent households (AORs ranged from 0.38 to 0.60). The results suggest that developing asset-based interventions tailored to the adolescents' family structure may be useful in preventing adolescents from engaging in ATODU.


Asunto(s)
Composición Familiar , Trastornos Relacionados con Sustancias , Humanos , Adolescente , Masculino , Femenino , Trastornos Relacionados con Sustancias/epidemiología , Estudios Longitudinales , Conducta del Adolescente/psicología , Estudios Prospectivos , Asunción de Riesgos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/psicología , Estructura Familiar
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA