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1.
Circulation ; 147(10): 812-823, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36700426

RESUMO

BACKGROUND: Benefit from cardiac resynchronization therapy (CRT) varies by QRS characteristics; individual randomized trials are underpowered to assess benefit for relatively small subgroups. METHODS: The authors analyzed patient-level data from pivotal CRT trials (MIRACLE [Multicenter InSync Randomized Clinical Evaluation], MIRACLE-ICD [Multicenter InSync ICD Randomized Clinical Evaluation], MIRACLE-ICD II [Multicenter InSync ICD Randomized Clinical Evaluation II], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure], BLOCK-HF [Biventricular Versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block], COMPANION [Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure], and MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy]) using Bayesian Hierarchical Weibull survival regression models to assess CRT benefit by QRS morphology (left bundle branch block [LBBB], n=4549; right bundle branch block [RBBB], n=691; and intraventricular conduction delay [IVCD], n=1024) and duration (with 150-ms partition). The continuous relationship between QRS duration and CRT benefit was also examined within subgroups defined by QRS morphology. The primary end point was time to heart failure hospitalization (HFH) or death; a secondary end point was time to all-cause death. RESULTS: Of 6264 patients included, 25% were women, the median age was 66 [interquartile range, 58 to 73] years, and 61% received CRT (with or without an implantable cardioverter defibrillator). CRT was associated with an overall lower risk of HFH or death (hazard ratio [HR], 0.73 [credible interval (CrI), 0.65 to 0.84]), and in subgroups of patients with QRS ≥150 ms and either LBBB (HR, 0.56 [CrI, 0.48 to 0.66]) or IVCD (HR, 0.59 [CrI, 0.39 to 0.89]), but not RBBB (HR 0.97 [CrI, 0.68 to 1.34]; Pinteraction <0.001). No significant association for CRT with HFH or death was observed when QRS was <150 ms (regardless of QRS morphology) or in the presence of RBBB. Similar relationships were observed for all-cause death. CONCLUSIONS: CRT is associated with reduced HFH or death in patients with QRS ≥150 ms and LBBB or IVCD, but not for those with RBBB. Aggregating RBBB and IVCD into a single "non-LBBB" category when selecting patients for CRT should be reconsidered. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT00271154, NCT00251251, NCT00267098, and NCT00180271.


Assuntos
Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Humanos , Feminino , Idoso , Masculino , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/terapia , Bloqueio de Ramo/complicações , Terapia de Ressincronização Cardíaca/efeitos adversos , Teorema de Bayes , Ensaios Clínicos Controlados Aleatórios como Assunto , Desfibriladores Implantáveis/efeitos adversos , Resultado do Tratamento , Eletrocardiografia
2.
Br J Haematol ; 204(6): 2365-2377, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38577874

RESUMO

Allogeneic haematopoietic cell transplantation (allo-HCT) remains an option for tyrosine kinase inhibitor-resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high-risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry-based study of 1686 CML patients undergoing first allo-HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo-HCT was 46 years (IQR 36-55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse-free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non-relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft-versus-host disease (GvHD)-free/relapse-free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Pessoa de Meia-Idade , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Adulto , Masculino , Feminino , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/etiologia , Transplante Homólogo , Sistema de Registros , Doadores de Tecidos , Doadores não Relacionados
3.
Artigo em Inglês | MEDLINE | ID: mdl-38898360

RESUMO

PURPOSE: To assess the reliability of excising residual breast cancer lesions after neoadjuvant systemic therapy (NAST) using a previously localized paramagnetic seed (Magseed®) and the subsequent use of contrast-enhanced spectral mammography (CESM) to evaluate response. METHODS: Observational, prospective, multicenter study including adult women (> 18 years) with invasive breast carcinoma undergoing NAST between January 2022 and February 2023 with non-palpable tumor lesions at surgery. Radiologists marked tumors with Magseed® during biopsy before NAST, and surgeons excised tumors guided by the Sentimag® magnetometer. CESMs were performed before and after NAST to evaluate tumor response (Response Evaluation Criteria for Solid Tumors [RECIST]). We considered intraoperative, surgical, and CESM-related variables and histological response. RESULTS: We analyzed 109 patients (median [IQR] age of 55.0 [46.0, 65.0] years). Magseed® was retrieved from breast tumors in all surgeries (100%; 95% CI 95.47-100.0%) with no displacement and was identified by radiology in 106 patients (97.24%), a median (IQR) of 176.5 (150.0, 216.3) days after marking. Most surgeries (94.49%) were conservative; they lasted a median (IQR) of 22.5 (14.75, 40.0) min (95% CI 23.59-30.11 min). Most dissected tumor margins (93.57%) were negative, and few patients (5.51%) needed reintervention. Magseed® was identified using CESM in all patients (100%); RECIST responses correlated with histopathological evaluations of dissected tumors using the Miller-Payne response grade (p < 0.0001) and residual lesion diameter (p < 0.0001). Also 69 patients (63.3%) answered a patient's satisfaction survey and 98.8% of them felt very satisfied with the entire procedure. CONCLUSION: Long-term marking of breast cancer lesions with Magseed® is a reliable and feasible method in patients undergoing NAST and may be used with subsequent CESM.

4.
Am Heart J ; 267: 81-90, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984672

RESUMO

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials. METHODS: Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n = 6,369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite end point of HFH or all-cause mortality or all-cause mortality alone was assessed. RESULTS: The median age was 67 years with 2436 (38%) being 70+; 1,554 (24%) were women; 2,586 (41%) had nonischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay in time to the composite end point (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66-0.85, P = .002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69-0.96, P = .017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either end point (P > .1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite end point (P for interaction = .027) with a similar but nonsignificant trend for mortality (P for interaction = .35). CONCLUSION: Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT.


Assuntos
Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Humanos , Feminino , Idoso , Masculino , Teorema de Bayes , Resultado do Tratamento , Insuficiência Cardíaca/terapia , Modelos de Riscos Proporcionais
5.
Cytometry A ; 105(5): 368-375, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38327134

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy is a breakthrough in hematologic malignancies, such as acute B lymphoblastic leukemia (B-ALL). Monitoring this treatment is recommended, although standardized protocols have not been developed yet. This work compares two flow cytometry monitoring strategies and correlates this technique with qPCR method. CAR-T cells were detected by two different flow-cytometry protocols (A and B) in nine blood samples from one healthy donor and five B-ALL patients treated with Tisagenlecleucel (Kymriah®, USA). HIV-1 viral load allowed CAR detection by qPCR, using samples from seven healthy donors and nine B-ALL patients. CAR detection by protocol A and B did not yield statistically significant differences (1.9% vs. 11.8% CD3 + CAR+, p = 0.07). However, protocol B showed a better discrimination of the CD3 + CAR+ population. A strong correlation was observed between protocol B and qPCR (r = 0.7, p < 0.0001). CD3 + CAR+ cells were detected by flow cytometry only when HIV-1 viral load was above 104 copies/mL. In conclusion, protocol B was the most specific flow-cytometry procedure for the identification of CAR-T cells and showed a high correlation with qPCR. Further efforts are needed to achieve a standardized monitoring approach.


Assuntos
Citometria de Fluxo , HIV-1 , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Linfócitos T , Carga Viral , Humanos , Citometria de Fluxo/métodos , Imunoterapia Adotiva/métodos , HIV-1/imunologia , HIV-1/genética , Carga Viral/métodos , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Complexo CD3 , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia
6.
Cytotherapy ; 26(1): 25-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37897472

RESUMO

BACKGROUND AIMS: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment. METHODS: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population. RESULTS: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. CONCLUSIONS: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia. TRIAL REGISTRATION: NCT04578210.


Assuntos
COVID-19 , Linfopenia , Humanos , SARS-CoV-2 , COVID-19/terapia , Células T de Memória , Resultado do Tratamento , Linfopenia/terapia , Antivirais
7.
Vox Sang ; 119(1): 27-33, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37986640

RESUMO

BACKGROUND AND OBJECTIVES: The efficacy of COVID-19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas-19 clinical trial showed that CP reduces the risk of progression to severe COVID-19 at 28 days. Here, we aim to study ConPlas-19 donors and characteristics that associate with high anti-SARS-CoV-2 antibody levels. MATERIALS AND METHODS: Four-hundred donors were enrolled in ConPlas-19. The presence and titres of anti-SARS-CoV-2 antibodies were evaluated by EUROIMMUN anti-SARS-CoV-2 S1 IgG ELISA. RESULTS: A majority of 80.3% of ConPlas-19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti-SARS-CoV-2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24-3.42), with more than 7 days of COVID-19 symptoms (RR 1.89; 95% CI 1.05-3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16-5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91-3.06). CONCLUSION: SARS-CoV-2 CP candidate donors' age, duration of COVID-19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID-19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks.


Assuntos
COVID-19 , SARS-CoV-2 , Feminino , Humanos , Masculino , Anticorpos Neutralizantes , Anticorpos Antivirais , Doadores de Sangue , COVID-19/terapia , Soroterapia para COVID-19 , Imunização Passiva/métodos , Imunoglobulina G , Ensaios Clínicos como Assunto
8.
Eur J Haematol ; 112(6): 910-916, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38333914

RESUMO

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a procedure with high morbidity and mortality. Identifying patients for maximum benefit and risk assessment is crucial in the decision-making process. This has led to the development of predictive risk models for HSCT in adults, which have limitations when applied to pediatric population. Our goal was to develop an automatic learning algorithm to predict survival in children with malignant disorders undergoing HSCT. METHODS: We studied allogenic HSCTs performed on children with malignant disorders at a third-level hospital between 1991 and 2021. Survival was analyzed using the Kaplan-Meier method, log-rank test for the univariate analysis, and Cox regression for the multivariate analysis. A prognostic index was constructed based on these findings. Lastly, we constructed a predictive model using a random forest algorithm to forecast 1-year survival after HSCT. RESULTS: We analyzed 229 HSCTs in 201 patients with a median follow-up of 1.64 years. Variables that impacted on the multivariate analysis were older age (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.12-1.76, p = .003), oldest period of HSCT (HR 0.46, 95% CI 0.29-0.73, p < .001), and mismatched donor (HR 2.65, 95% CI 1.51-4.65, p = .001). Our prognostic index was associated with 3-year overall survival (OS; p < .001). A random forest was developed using as variables: diagnosis, age, year of HSCT, time from diagnosis to HSCT, disease stage, donor type, and conditioning. This achieved 72% accuracy in predicting 1-year OS. CONCLUSIONS: Our index and random forest was effective in predicting 1-year survival. However, further validation in diverse populations is necessary to establish their generalizability.


Assuntos
Inteligência Artificial , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Criança , Pré-Escolar , Adolescente , Prognóstico , Lactente , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais
9.
Eur J Clin Microbiol Infect Dis ; 43(3): 533-540, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38236366

RESUMO

PURPOSE: To describe a cohort with a high risk of recurrence who received bezlotoxumab during the first episode of Clostridioides difficile infection (CDI) and to compare this cohort with patients with similar characteristics who did not receive the monoclonal antibody. METHODS: A prospective and multicentre study of patients with a high risk of recurrence (expected recurrence rate>35%) who were treated with bezlotoxumab during their first episode of CDI was conducted. A propensity score-matched model 1:2 was used to compare both cohorts that were weighed according to basal characteristics (hospital-acquisition, creatinine value, and fidaxomicin as a CDI treatment). RESULTS: Sixty patients (mean age:72 years) were prospectively treated with bezlotoxumab plus anti-Clostridioides antibiotic therapy. Vancomycin (48 patients) and fidaxomicin (12 patients) were prescribed for CDI treatment, and bezlotoxumab was administered at a mean of 4.2 (SD:2.1) days from the beginning of therapy. Recurrence occurred in nine out of 54 (16.7%) evaluable patients at 8 weeks. Forty bezlotoxumab-treated patients were matched with 69 non-bezlotoxumab-treated patients. Recurrence rates at 12 weeks were 15.0% (6/40) in bezlotoxumab-treated patients vs. 23.2% (16/69) in non-bezlotoxumab-treated patients (OR:0.58 [0.20-1.65]). No adverse effects were observed related to bezlotoxumab infusion. Only one of 9 patients with previous heart failure developed heart failure. CONCLUSION: We observed that patients treated with bezlotoxumab in a real-world setting during a first episode of CDI having high risk of recurrence, presented low rate of recurrence. However, a significant difference in recurrence could not be proved in comparison to the controls. We did not detect any other safety concerns.


Assuntos
Anticorpos Amplamente Neutralizantes , Infecções por Clostridium , Insuficiência Cardíaca , Humanos , Idoso , Fidaxomicina/uso terapêutico , Estudos Prospectivos , Recidiva , Antibacterianos/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Infecções por Clostridium/microbiologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico
10.
Dig Dis Sci ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877333

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure, but it poses challenges in patients with surgically altered gastrointestinal anatomy (SAGA). Alternative techniques like single-balloon enteroscopy (SBE), double-balloon enteroscopy (DBE), or push enteroscopy (PE) have been used, albeit with potential complications. Limited Latin American data exists on ERCP complications in SAGA patients. Our goal is to describe complications of ERCP in SAGA at a national referral institution. METHODS: Retrospective, single-center cohort study. All SAGA ERCP procedures performed at the Gastrointestinal Endoscopy Department of the National Institute of Medical Sciences and Nutrition Salvador Zubirán from January 2008 to May 2023 were included. Extracted data from records included procedure specifics, endoscope type, success, and complications. Complications were evaluated during procedure and 28-day post-procedure and classified using the AGREE system. RESULTS: A total of 266 procedures in 174 patients were included, 74% were women, and the median age was 44 years. Predominant modified anatomy was Roux-en-Y biliary reconstruction (79%), followed by Whipple procedure (13%) and subtotal gastrectomy with Roux-en-Y reconstruction (6.0%). The main indications were cholangitis with stricture (31%), stricture (19%), and cholangitis (19%). DBE was used in 89%, PE in 7.5%, and SBE in 3.4%. Success rates were 77% endoscopic, 72% technical, and 69% therapeutic; in 30%, the procedure was unsuccessful. Complications happened in 18% of cases, most commonly cholangitis (7.5%), followed by perforation (2.6%) and hemorrhage (1.9%). According to the AGREE classification, 10.9% were grades 1 and 2, 6.4% were grade 3, and 0.4% were grade 4 complications. No significant differences emerged between groups with and without complications. Procedures increased over time, but complications and unsuccessful procedures remained stable. CONCLUSION: ERCP complications align with international data, often not requiring invasive treatment. Enhanced exposure to such cases correlates with fewer complications and failures. Prospective studies are essential to identify complication and failure predictors.

11.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33536339

RESUMO

Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatiotemporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, normalized distance from 18F-fluorodeoxyglucose (18F-FDG) hotspot to centroid (NHOC), based on the separation from the location of the activity (proliferation) hotspot to the tumor centroid. The NHOC metric can be computed for patients using 18F-FDG PET-computed tomography (PET/CT) images where the voxel of maximum uptake (standardized uptake value [SUV]max) is taken as the activity hotspot. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non-small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NHOC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers additional insights into the evolutionary mechanisms behind tumor progression, provides a different PET/CT-based biomarker, and reveals that an activity hotspot closer to the tumor periphery is associated to a worst patient outcome.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Modelos Teóricos , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/genética , Feminino , Fluordesoxiglucose F18/farmacologia , Heterogeneidade Genética/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prognóstico
12.
Anaerobe ; 85: 102816, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38145709

RESUMO

The aim of this study was to describe the in vitro activity of delafloxacin against 230 anaerobic isolates and compare it with the activity of other antimicrobials used against infections caused by anaerobic microorganisms. Minimal inhibitory concentrations (MICs) were lower for delafloxacin than for all other antibiotics tested with the exception of piperacillin-tazobactam and meropenem against Gram-positive anaerobic cocci. Only two (0.8 %) isolates of Bacteroides spp. showed a MIC ≥4 µg/mL. With some exceptions, the present results show lower MICs for delafloxacin in comparison to the other antibiotics used against anaerobes.


Assuntos
Anti-Infecciosos , Infecções Bacterianas , Fluoroquinolonas , Cocos Gram-Positivos , Humanos , Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Bactérias Anaeróbias , Testes de Sensibilidade Microbiana
13.
J Allergy Clin Immunol ; 152(4): 997-1009.e11, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37301410

RESUMO

BACKGROUND: Inborn errors of immunity (IEI) are a group of monogenic diseases that confer susceptibility to infection, autoimmunity, and cancer. Despite the life-threatening consequences of some IEI, their genetic cause remains unknown in many patients. OBJECTIVE: We investigated a patient with an IEI of unknown genetic etiology. METHODS: Whole-exome sequencing identified a homozygous missense mutation of the gene encoding ezrin (EZR), substituting a threonine for an alanine at position 129. RESULTS: Ezrin is one of the subunits of the ezrin, radixin, and moesin (ERM) complex. The ERM complex links the plasma membrane to the cytoskeleton and is crucial for the assembly of an efficient immune response. The A129T mutation abolishes basal phosphorylation and decreases calcium signaling, leading to complete loss of function. Consistent with the pleiotropic function of ezrin in myriad immune cells, multidimensional immunophenotyping by mass and flow cytometry revealed that in addition to hypogammaglobulinemia, the patient had low frequencies of switched memory B cells, CD4+ and CD8+ T cells, MAIT, γδ T cells, and centralnaive CD4+ cells. CONCLUSIONS: Autosomal-recessive human ezrin deficiency is a newly recognized genetic cause of B-cell deficiency affecting cellular and humoral immunity.


Assuntos
Linfócitos T CD8-Positivos , Citoesqueleto , Humanos , Citoesqueleto/metabolismo , Membrana Celular/metabolismo , Imunidade Humoral
14.
J Pediatr Nurs ; 76: 114-123, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38377918

RESUMO

INTRODUCTION: Establishing an adequate bond and attachment between a mother and child is essential for preventing pathologies and developing this relationship in the future. PURPOSE: To identify the factors related to a disturbance of the mother-child bond or attachment. METHODS: A cross-sectional descriptive study was carried out with women with a biological child between 6 weeks and 18 months of age. The Mother-Child Bond-Attachment Questionnaire (VAMF, for its name in Spanish) was administered to measure the bond and postnatal attachment together with a questionnaire containing sociodemographic, psychosocial, and health variables referring to the mother and the newborn. RESULTS: 1114 women participated. The multivariate analysis showed that skin-to-skin contact (aOR = 0.58; 95% CI: 0.37, 0.90) and breastfeeding (aOR = 0.55; 95% IC: 0.35, 0.86) reduce the probability of presenting a bond disturbance. Anxiety during pregnancy, childbirth, and the puerperium (aOR = 3.95; 95% CI: 2.57, 6.05) and postpartum complications (aOR = 1.60; 95% CI: 1.03, 2.48) increase the chance of having a bond disturbance. Skin-to-skin contact (aOR = 0.61; 95% CI: 0.38, 1.00), breastfeeding (aOR = 0.47; 95% CI: 0.27, 0.80,) and an older age of the infant (months) (aOR = 0.77: 95% CI: 0.72, 0.82) reduces the probability of presenting an attachment disturbance. CONCLUSIONS: Skin-to-skin contact and breastfeeding are associated with a lower probability of impaired bonding and attachment. Anxiety states during pregnancy, childbirth, and the puerperium, and complications after childbirth increase the probability of developing a bond disorder. The older the age of the infant, the lower the frequency of having an impaired attachment. IMPLICATIONS TO PRACTICE: Identifying the factors associated with the establishment of the mother-child bond and attachment is essential for the development of prevention strategies and early identification of cases that may present alterations and avoid their consequences on the health of the mother and child.


Assuntos
Aleitamento Materno , Relações Mãe-Filho , Apego ao Objeto , Humanos , Feminino , Estudos Transversais , Adulto , Lactente , Inquéritos e Questionários , Aleitamento Materno/psicologia , Aleitamento Materno/estatística & dados numéricos , Recém-Nascido , Gravidez , Espanha , Mães/psicologia , Adulto Jovem , Análise Multivariada
15.
BMC Nurs ; 23(1): 202, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38528510

RESUMO

BACKGROUND: There are recommendations based on scientific evidence on care in the second stage of labor, but it is not known to what degree the professionals comply with these recommendations. OBJECTIVE: The aim of this study is to examine the variability in clinical practices among midwives during the second stage of labor, including positions, mobility, practices, and the maximum time allowed before initiating active pushing, and to assess their adherence to clinical practice guidelines. METHODS: A cross-sectional observational study. A self-designed questionnaire was developed and distributed online through scientific societies. The main variables studied were professional and work environment characteristics, maternal positions and mobility, practices during this stage, maximum time to start active pushing and duration of the second stage of labor. Descriptive statistics were calculated using SPSS 24.0. RESULTS: Regarding the woman's position during childbirth, 80.3% (245) of midwives frequently or always allow the woman to choose her birthing position. Furthermore, 44.6% (136) of professionals prefer using side-lying positions for the mother. Regarding drinking fluids during childbirth, 51.1% (156) of midwives allowed the woman to drink the amount of liquids she wanted, whereas 11.1% (34) said that they would allow them to do so however, this was against the protocol of their hospital. When inquiring about the Kristeller maneuver, it was reported to be excessively performed in 35.1% (107) of cases for fetal bradycardia, 33.1% (101) for maternal exhaustion, and 38.4% (117) to avoid instrumental birth. Finally, a great variability was observed in the time criteria used for the initiation of active pushing and the maximum duration of the second stage of labor. CONCLUSIONS: Certain practices, such as the Kristeller maneuver, are overused among midwives, with great variability in the use of certain procedures, the waiting times to initiate pushing and completion of the second stage of labor. Further training and awareness campaigns are needed for professionals to apply evidence-based care.

16.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38218430

RESUMO

It is widely acknowledged that inflammatory bowel disease (IBD) is associated with a high prevalence of sexual dysfunction (SD). However, there is a notable paucity of specific literature in this field. This lack of information impacts various aspects, including the understanding and comprehensive care of SD in the context of IBD. Furthermore, patients themselves express a lack of necessary attention in this area within the treatment of their disease, thus creating an unmet need in terms of their well-being. The aim of this position statement by the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) is to provide a review on the most relevant aspects and potential areas of improvement in the detection, assessment, and management of SD in patients with IBD and to integrate the approach to sexual health into our clinical practice. Recommendations are established based on available scientific evidence and expert opinion. The development of these recommendations by GETECCU has been carried out through a collaborative multidisciplinary approach involving gastroenterologists, gynecologists, urologists, surgeons, nurses, psychologists, sexologists, and, of course, patients with IBD.

17.
Nurs Health Sci ; 26(2): e13116, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38566393

RESUMO

To understand the experience, training, and needs of midwives in their approach to perinatal grief. A descriptive cross-sectional study was carried out using an online questionnaire with 26 questions related to institutional management and individual clinical practices in the care of a perinatal loss was developed by a team of midwives from the Hospital "La Mancha-Centro" of Alcazar de San Juan (Ciudad Real). Strobe checklist was followed. A total of 267 midwives participated. A total of 92.1% (246) of the centers had specific protocols for action, but each professional applied their own criteria. The presence of a perinatal psychology team was nonexistent according to 88% (235) of those surveyed. Regarding their training and professional experience, 16.5% (44) of the midwives had never received training. Only 4.1% (11) of the midwives felt very prepared to care for women with a perinatal loss. Among the factors associated with greater application of recommended practices in the face of perinatal death by midwives were being a woman, having prior training on care during perinatal death, and a greater perception of preparation (p < 0.05). The perception of lack of preparation on the part of midwives in the accompaniment of these families was high.


Assuntos
Tocologia , Morte Perinatal , Gravidez , Humanos , Feminino , Recém-Nascido , Criança , Estudos Transversais , Ansiedade , Inquéritos e Questionários , Assistência Perinatal/métodos
18.
Rev Invest Clin ; 76(1): 18-28, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38262366

RESUMO

Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.


Assuntos
Hemocromatose , Sobrecarga de Ferro , Hepatopatias , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Hemocromatose/complicações , Hemocromatose/epidemiologia , Hemocromatose/patologia , Estudos Retrospectivos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/complicações , Hepatopatias/complicações , Hepatopatias/metabolismo , Hepatopatias/patologia , Fígado/metabolismo
19.
Gac Med Mex ; 160(1): 76-85, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753554

RESUMO

BACKGROUND: Chromosomal abnormalities are present in 50 to 60% of miscarriages and in 6 to 19% of stillbirths. Although microarrays are preferred for studying chromosomal abnormalities, many hospitals cannot offer this methodology. OBJECTIVE: To present the results of the cytogenetic analysis of 303 products of conception (POC), which included 184 miscarriages, 49 stillbirths and 17 cases of undefined age. MATERIAL AND METHODS: Karyotyping, fluorescence in situ hybridization, short tandem repeats and microarrays were used, depending on the type of loss and available sample. RESULTS: In 29 POCs we found maternal tissue and were eliminated from the analyses. Informative results were obtained in 250 (91.2 %)/274 cases; the karyotyping success rate was 80.7%; that of single nucleotide polymorphism microarrays, 94.5%; and that of fluorescence in situ hybridization and short tandem repeat, 100%. Cytogenetic abnormalities were observed in 57.6% of miscarriages and in 24.5% of stillbirths; 94% of total anomalies were numerical and 6% were submicroscopic. CONCLUSIONS: Karyotyping with simultaneous short tandem repeat study to rule out contamination of maternal cells is effective for studying miscarriages; in stillbirths, microarrays are recommended.


ANTECEDENTES: Las alteraciones cromosómicas están presentes en 50 a 60 % de los abortos espontáneos y en 6 a 19 % de los mortinatos. Aunque se prefieren los microarreglos para estudiarlos, numerosos hospitales no pueden ofrecerlos. OBJETIVO: Presentar los resultados del estudio citogenético de 303 productos de la concepción (POC), 184 se obtuvieron de abortos espontáneos, 49 fueron mortinatos y en 17 no se identificó la de edad gestacional. MATERIAL Y MÉTODOS: Se empleó cariotipo, hibridación in situ con fluorescencia, secuencias cortas repetidas en tándem y microarreglos, según el tipo de pérdida y la muestra disponible. RESULTADOS: En 29 POC se encontró tejido materno, por lo que fueron eliminados de los análisis. En 250 (91.2 %)/274 casos se obtuvieron resultados informativos; la tasa de éxito del cariotipo fue de 80.7 %; la de los microarreglos de SNP, de 94.5 %; y la de la hibridación fluorescente in situ y la repetición corta en tándem, de 100 %. Se observaron anomalías citogenéticas en 57.6 % de los abortos espontáneos y en 24.5 % de los mortinatos; 94 % de las anomalías fueron numéricas y 6 %, submicroscópicas. CONCLUSIONES: El cariotipo en conjunto con el estudio de secuencias cortas repetidas en tándem para descartar contaminación de células maternas es efectivo para estudiar abortos espontáneos; los microarreglos se recomiendan en los mortinatos.


Assuntos
Aborto Espontâneo , Aberrações Cromossômicas , Hibridização in Situ Fluorescente , Cariotipagem , Humanos , Feminino , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/genética , México/epidemiologia , Gravidez , Cariotipagem/métodos , Natimorto/genética , Natimorto/epidemiologia , Adulto , Análise Citogenética/métodos , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Adulto Jovem
20.
Ann Surg ; 277(1): e235-e244, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34171860

RESUMO

OBJECTIVE: We aimed to assess whether native spleen preservation during visceral transplantation (VT) affects graft-versus-host-disease (GVHD) incidence. SUMMARY BACKGROUND DATA: GVHD is one of the most severe and frequently lethal hematological complications after VT procedures. Because there is no specific treatment for GVHD, it is imperative to develop a strategy to reduce donor lymphocyte engraftment and proliferation. METHODS: Our study included both clinical and experimental data. A total of 108 patients were divided into 3 groups: a native spleen preservation group, a native spleen removal with no donor spleen group, and a donor spleen included (allogeneic spleen) group. We also used an allogeneic VT rat model, in which recipients were divided into 2 groups: a native spleen preservation (+SP) group and a native spleen removal (-S) group. Skin rash appearance, histopathological changes, chimerism, and spleen effects on circulating allogeneic T-cells were assessed. RESULTS: The patients with native spleen preservation showed a lower rate of GVHD ( P <.001) and better survival ( P <.05) than those in the other groups. Skin and histological signs of GVHD were lower in the rats in the +SP group ( P <.05). The donor T-cell frequency in the bloodstream and skin was also significantly reduced when the native spleen was preserved ( P <.01 and P <.0001, respectively). CONCLUSIONS: The clinical and experimental data indicate that recipient spleen preservation protects against GVHD after VT, and donor cell clearance from the bloodstream by spleen macrophages could be the underlying mechanism. Therefore, spleen preservation should be considered in VT procedures, whenever possible.


Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro , Ratos , Animais , Camundongos , Baço , Transplante Homólogo , Linfócitos T , Camundongos Endogâmicos C57BL
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