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BACKGROUND: Drug-drug interactions between antiretroviral treatment (ART) and cytostatics may have a negative impact in the prognosis of people with HIV (PWH) and cancer. OBJECTIVE: The objective of this study is to evaluate the impact of the implementation of interdisciplinary management and the type of ART in PWH diagnosed with lymphoid neoplasms. METHODS: This is a multicentric, retrospective observational cohort study including PWH diagnosed with lymphoid neoplasm who started first-line chemotherapy between 2008 and 2020. Demographic, clinical and therapeutic variables were obtained from the electronic medical records and associated with 5-year progression-free survival (PFS) and overall survival (OS) using Cox proportional hazard models. RESULTS: A total of 118 individuals were included. Boosted ART was being used in 55 (46.6%) cases at the time of neoplasm diagnosis. The Infectious Diseases or the Pharmacy Department was consulted before starting chemotherapy in 79/118 (66.9%) cases. Interdisciplinary management resulted in fewer subjects taking boosted ART (17.7% versus 71.8%, Pâ<â0.001) and more subjects using unboosted integrase strand transfer inhibitor-based ART (74.7% versus 7.7%, Pâ<â0.001). The use of boosted ART with chemotherapy was associated with worse 5-year PFS (Pâ=â0.003) and 5-year OS (Pâ=â0.016). There was a trend towards better 5-year PFS and OS when interdisciplinary management was implemented, with significant differences for individuals receiving boosted ART at neoplasm diagnosis (Pâ=â0.0246 and Pâ=â0.0329, respectively). CONCLUSIONS: Our findings underscore the significant impact of the type of ART on the prognosis of PWH undergoing chemotherapy. Encouraging collaborative management between oncologists, pharmacists and HIV teams for these patients enhances PFS and OS rates.
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INTRODUCTION: Rapid initiation of ART after HIV diagnosis is recommended for individual and public health benefits. However, certain clinical and ART-related considerations hinder immediate initiation of therapy. METHODS: An open-label, single-arm, single-centre 48-week prospective clinical trial involving ART-naïve HIV-diagnosed adults who started bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) within a week from the first hospital visit, before the availability of baseline laboratory and genotype results. The primary aim was to determine the proportion of people with at least one condition that would hinder immediate initiation of any recommended ART regimen other than BIC/FTC/TAF. Clinicaltrials.gov: NCT04416906. RESULTS: We included 100 participants: 79% men, 64% from Latin America, median age 32 years. According to European AIDS Clinical Society (EACS) and US Department of Health and Human Services 2023 guidelines, 11% (95%CI 6; 19) of participants had at least one condition that made any ART different from BIC/FTC/TAF less appropriate for a rapid ART strategy. Seventy-nine percent of the people started BIC/FTC/TAF within the first 48 hours of their first hospital visit. There were 16 early discontinuations (11 lost to follow-up). By week 48, 92% (95%CI 86; 98) of the participants of the ITT population with observed data achieved viral suppression. Eight grade 3-4 adverse events (AEs), five serious AEs and six ART-related AEs were identified. Adherence remained high. CONCLUSIONS: BIC/FTC/TAF is an optimal treatment for rapid initiation of ART. However, additional strategies to improve retention in care must be implemented.
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Alanina , Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Piridonas , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Masculino , Adulto , Estudos Prospectivos , Feminino , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Piridonas/administração & dosagem , Alanina/uso terapêutico , Alanina/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Piperazinas/administração & dosagem , Amidas/administração & dosagem , Amidas/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/administração & dosagem , Adenina/efeitos adversos , Combinação de Medicamentos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Pessoa de Meia-Idade , Adulto Jovem , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the 'chemsex' context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization. CLINICAL FINDING: After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3 mg/dl - elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3 weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1. CONCLUSIONS: The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.
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BACKGROUND: Decreasing medication burden with raltegravir plus lamivudine in virologically suppressed persons with HIV (PWH) maintained efficacy and was well tolerated at 24 weeks, but more comprehensive data over longer follow-up are required. METHODS: Prospective 48 week extension phase of the raltegravir plus lamivudine arm from a previous 24 week pilot randomized clinical trial in which virologically suppressed PWH were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. In this 48 week extension phase, raltegravir was dosed at 1200 mg/day and lamivudine 300 mg/day. Primary outcome was the proportion of PWH with treatment failure at Week 48. Secondary outcomes were changes in ultrasensitive plasma HIV RNA, HIV DNA in CD4 cells, serum IL-6, ultrasensitive C-reactive protein and sCD14, body composition, sleep quality, quality of life and adverse effects. RESULTS: Between May 2018 and June 2019, 33 PWH were enrolled. One participant experienced virological failure without resistance mutations and re-achieved sustained virological suppression without therapy discontinuation, and two others discontinued therapy due to adverse effects. Treatment failure was 9% (95% CI 2%-24%) and 3% (95% CI 0%-17%) in the ITT and on-treatment populations. There were significant changes between baseline and Week 48 in serum cytokines but not in other secondary outcomes. CONCLUSIONS: Switching to raltegravir and lamivudine in PWH with virological suppression maintains efficacy and is well tolerated. This maintenance regimen might be a cost-effective option for PWH at risk of drug-drug interactions or needing to avoid specific toxicities of certain antiretroviral drugs or their negative impact on comorbidities.
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Fármacos Anti-HIV , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Humanos , Raltegravir Potássico/efeitos adversos , Lamivudina/efeitos adversos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Quimioterapia Combinada , Carga Viral , Resultado do TratamentoRESUMO
BACKGROUND: Time intervals and number of prior consultations in primary care (PC) are recognised metrics of diagnostic timeliness of cancer and are interrelated. However, whether and how the two measures correlate with each other in the emergency diagnostic pathway is unknown. We investigated the association between the number of prereferral consultations and the length of intervals from PC presentation to cancer diagnosis following emergency referral to hospital. METHODS: Patients were eligible if they first consulted in PC and were diagnosed with cancer following emergency or nonemergency referral to hospital. We analysed for differences in PC and diagnostic intervals and number of consultations between emergency and nonemergency presenters and determined their associations by cancer type. Differences in presenting symptoms and stage at diagnosis between populations and according to number of consultations were also examined. RESULTS: There were 796 emergency and 865 nonemergency presenters with comparable sociodemographic and comorbidity data. Correlation analysis in emergency presenters revealed a strong positive association between number of consultations and intervals for seven of 13 different cancers, including cancers characterised by high proportions of > 3 consultations and long intervals (pancreatic, lung, and colorectal cancer) and vice versa for others (e.g., endometrial, cervical, or oesophageal cancer). Additionally, emergency presenters with > 3 consultations were more likely than those with 1-2 to report nonspecific symptoms (60 vs. 40%, respectively) and to be diagnosed at a later stage. CONCLUSION: System level interventions are needed to reduce unnecessary delays in the emergency diagnostic pathway, particularly in cancer patients with multiple prereferral consultations. The findings also suggest opportunities to reduce the proportion of emergency diagnoses by targeting symptomatic individuals pre-presentation.
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Detecção Precoce de Câncer , Neoplasias Esofágicas , Humanos , Diagnóstico Tardio , Encaminhamento e Consulta , Atenção Primária à SaúdeRESUMO
Subjective ultrasound assessment by an expert examiner is meant to be the best option for the differentiation between benign and malignant adnexal masses. Different ultrasound scores can help in the classification, but whether one of them is significantly better than others is still a matter of debate. The main aim of this work is to compare the diagnostic performance of some of these scores in the evaluation of adnexal masses in the same set of patients. This is a retrospective study of a consecutive series of women diagnosed as having a persistent adnexal mass and managed surgically. Ultrasound characteristics were analyzed according to IOTA criteria. Masses were classified according to the subjective impression of the sonographer and other ultrasound scores (IOTA simple rules -SR-, IOTA simple rules risk assessment -SRRA-, O-RADS classification, and ADNEX model -with and without CA125 value-). A total of 122 women were included. Sixty-two women were postmenopausal (50.8%). Eighty-one women had a benign mass (66.4%), and 41 (33.6%) had a malignant tumor. The sensitivity of subjective assessment, IOTA SR, IOTA SRRA, and ADNEX model with or without CA125 and O-RADS was 87.8%, 66.7%, 78.1%, 95.1%, 87.8%, and 90.2%, respectively. The specificity for these approaches was 69.1%, 89.2%, 72.8%, 74.1%, 67.9%, and 60.5%, respectively. All methods with similar AUC (0.81, 0.78, 0.80, 0.88, 0.84, and 0.75, respectively). We concluded that IOTA SR, IOTA SRRA, and ADNEX models with or without CA125 and O-RADS can help in the differentiation of benign and malignant masses, and their performance is similar to the subjective assessment of an experienced sonographer.
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COVID-19/terapia , Hospitais Públicos/organização & administração , Hospitais de Ensino/organização & administração , Hospitais Urbanos/organização & administração , Transferência de Pacientes , Idoso , Feminino , Número de Leitos em Hospital , Humanos , Masculino , Pessoa de Meia-Idade , Quarentena , SARS-CoV-2 , Índice de Gravidade de Doença , EspanhaRESUMO
Alternatives to conventional hospitalization are needed to increase health systems resilience in the face of COVID-19 pandemic. Herein, we describe the characteristics and outcomes of 63 patients admitted to a single HaH during the peak of COVID-19 in Barcelona. Our results suggest that HaH seems to be a safe and efficacious alternative to conventional hospitalization for accurately selected patients with COVID-19.
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COVID-19/terapia , Serviços Hospitalares de Assistência Domiciliar/estatística & dados numéricos , Adulto , COVID-19/diagnóstico , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Espanha/epidemiologia , Resultado do TratamentoRESUMO
Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and -positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes.
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Carcinoma Ductal de Mama/metabolismo , Linfonodos/metabolismo , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Humanos , Imuno-Histoquímica , Metástase Linfática/fisiopatologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The introduction of high-throughput techniques is increasingly providing abundant information on molecular alterations requiring validation at the posttranscriptional level. Protein expression is now efficiently evaluated in large series of tumors included in tissue microarrays. We propose, describe and validate a technique to elaborate paraffin-embedded cell line microarrays (PECLIMA) from fixed cell cultures, which can be processed like standard surgical pathology biopsies prior to immunophenotyping. Our results show a reliable protein immunoexpression profiling in six widely used cell lines under different fixation conditions. This technique permits the simultaneous analysis of multiple antigens in multiple cell lines under different experimental conditions. Additional features of these arrays are long-term storage, their suitability for a variety of techniques including immunocytochemistry and in situ hybridization and their low cost.