Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
Cancer Control ; 31: 10732748241274190, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39150340

RESUMO

The treatment of metastatic castration-sensitive prostate cancer (mCSPC) has seen remarkable breakthroughs over the last few years. Diagnostic and therapeutic advances have given rise to debates about risk stratification and optimal first-line treatment selection, as well as to concerns about potential overtreatment in a disease state with a highly heterogeneous clinical behavior. Here, we use case reports from our practice to review the clinical trials exploring intensified triplet regimens combining androgen deprivation therapy with second-generation androgen receptor signaling inhibitors and docetaxel, and we offer our recommendations on how to best select candidates for these novel combinations. Furthermore, the growing adoption of PET imaging with increasingly sensitive and prostate tissue-specific tracers replacing conventional staging technologies has led to the identification of a subset of low-volume mCSPC with nodal metastases which would otherwise not be considered abnormal by RECIST criteria. We describe our PSA-adapted approach to treatment in this unique population with non-measurable low-volume mCSPC which has not been specifically investigated in any phase III clinical trials. We also discuss ongoing clinical trials evaluating treatment de-escalation strategies. Finally, we review how local treatment modalities directed at the prostate or distant sites of disease in oligometastatic CSPC may benefit patients, and how we incorporate metastasis-directed therapy in the management of mCSPC.


Assuntos
Metástase Neoplásica , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Antagonistas de Androgênios/uso terapêutico , Docetaxel/uso terapêutico , Docetaxel/administração & dosagem
2.
Lung ; 201(3): 309-314, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37300706

RESUMO

PURPOSE: Ventilator weaning protocols rely in part on objective indices to best predict extubation failure in the critically ill. We investigated static respiratory system compliance (RC) as a predictor of extubation failure, in comparison to extubation readiness using rapid shallow breathing index (RSBI). MATERIAL AND METHODS: This was a cross-sectional, multi-institutional study of mechanically ventilated patients admitted between 12/01/2017 and 12/01/2019. All patients older than 18 years with a documented spontaneous breathing trial and extubation trial were included. RC and RSBI were calculated prior to the extubation trial. The primary outcome was extubation failure-defined as need for reintubation within 72 h from time of extubation. RESULTS: Of the 2263 patients, 55.8% were males with a mean age of 68 years. The population consisted mostly of Caucasians (73%) and African Americans (20.4%). 274 (12.1%) patients required reintubation within 72 h. On multivariate logistic regression after adjusting for age, sex, body mass index (BMI), admission Sequential Organ Failure Assessment (SOFA) score, number of ventilator days, and the P/F ratio on the day of extubation, RC remained the strongest predictor for extubation failure at 24 h (aOR 1.45; 95% CI 1.00-2.10) and 72 h (aOR 1.58; 95% CI 1.15-2.17). There was no significant association between RSBI and extubation failure at 24 (aOR 1.00; 95% CI 0.99-1.01) or at 72 h (aOR 1.00; 95% CI 0.99-1.01). CONCLUSION: RC measured on the day of extubation is a promising physiological discriminant to potentially risk stratify patients with acute respiratory failure for extubation readiness. We recommend further validation studies in prospective cohorts.


Assuntos
Extubação , Insuficiência Respiratória , Idoso , Feminino , Humanos , Masculino , Extubação/métodos , Estudos Transversais , Estudos Prospectivos , Respiração Artificial , Insuficiência Respiratória/terapia , Sistema Respiratório , Desmame do Respirador/métodos
3.
Eur J Haematol ; 109(3): 282-288, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35617049

RESUMO

INTRODUCTION: Sickle trait (Hb SA) or sickle disease (Hb SS) carries increased risk of venous thromboembolism (VTE). Hb SS patients are young and lack common comorbid conditions that qualify them for VTE prophylaxis (VTEP). METHODS: Retrospective, multicenter analysis of Hb SS/Hb SA adult patients between January 2013 and December 2018. RESULTS: There were 803 Hb SA (525 patients) and 1020 Hb SS admissions (262 patients). VTEP use was similar between Hb SA and controls (42% vs. 46%; p-value = .06) and Hb SS and controls (45% vs. 42%; p-value = .13). Hb SS/Hb SA patients more frequently received more than half of prescribed doses of VTEP. In multivariate analysis, increasing age and longer hospitalizations were positive predictors. Odds of VTEP use varied with treatment site for Hb SS patients, whereas comorbid conditions, admission hemoglobin and platelet count were not predictive. By contrast, in Hb SA patients, comorbid conditions, higher admission hemoglobin, and higher admission platelet counts raised the odds of VTEP being offered. CONCLUSIONS: VTEP is underused in Hb SS/Hb SA patients. There may be a trend toward offering more VTEP in Hb SS disease, but not in Hb SA patients, where VTEP prescribing is driven by comorbid conditions rather than genotype. Patient compliance does not appear to play a major role, but intercenter variability suggests provider education may improve VTEP use.


Assuntos
Anemia Falciforme , Traço Falciforme , Tromboembolia Venosa , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Anticoagulantes/uso terapêutico , Hospitalização , Humanos , Estudos Retrospectivos , Traço Falciforme/complicações , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
4.
Eur J Haematol ; 106(5): 689-696, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33569825

RESUMO

BACKGROUND: Data on the safety of apixaban compared to warfarin in hemodialysis (HD) patients are accumulating, but the impact of concomitant antiplatelet use is unknown. OBJECTIVES: Compare hemorrhagic risk and impact of antiplatelets in HD patients receiving oral anticoagulants (OAC). METHODS: Retrospective, multi-center study of HD patients started on OAC inpatient over 5 years. RESULTS: 707 patients were included: 563 received warfarin, and 144 received apixaban. 197 had bleeding, most in the warfarin group (173 [30.1%] vs 24 [16.7%] in the apixaban group), P-value < .01). However, with concomitant antiplatelet use, frequencies were similar (31.4% vs 25.0%; P-value = .292). Cumulative incidence using bleeding as event of interest and death as competing risk showed higher rates of bleeding with warfarin. In a multivariate model, apixaban was associated with a lower hemorrhagic risk (hazard ratio [HR] 0.55 [95% confidence interval {CI} 0.35-0.86}). Apixaban showed lower hemorrhagic risk alone (HR 0.24, 95% CI 0.10-0.55) and similar risk when administered with antiplatelets (HR 0.93, 95% CI 0.55-1.56). CONCLUSIONS: Apixaban is associated with less bleeding in HD patients compared to warfarin, but concomitant antiplatelet use may negate the safety advantage. Prospective trials are warranted to determine the impact of antiplatelets on apixaban safety.


Assuntos
Anticoagulantes/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Diálise Renal , Varfarina/efeitos adversos , Administração Oral , Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Inibidores do Fator Xa/administração & dosagem , Feminino , Pesquisas sobre Atenção à Saúde , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Medição de Risco , Varfarina/administração & dosagem
5.
Eur J Haematol ; 106(2): 165-174, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33043484

RESUMO

BACKGROUND: Hypercoagulability may contribute to COVID-19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. OBJECTIVES: We evaluated the impact on survival of different AC doses in COVID-19 patients. METHODS: Retrospective, multi-center cohort study of consecutive COVID-19 patients hospitalized between March 13 and May 5, 2020. RESULTS: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated different 25-day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS-weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. CONCLUSIONS: Higher doses of AC were associated with lower mortality in hospitalized COVID-19 patients. Prospective evaluation of efficacy and risk of AC in COVID-19 is warranted.


Assuntos
Anticoagulantes , Tratamento Farmacológico da COVID-19 , COVID-19 , Hemorragia , Mortalidade Hospitalar , Unidades de Terapia Intensiva , SARS-CoV-2/metabolismo , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , COVID-19/sangue , COVID-19/complicações , COVID-19/mortalidade , Intervalo Livre de Doença , Feminino , Hemorragia/sangue , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida
6.
J Intensive Care Med ; 36(9): 1018-1024, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34074160

RESUMO

PURPOSE: We sought to identify clinical factors that predict extubation failure (reintubation) and its prognostic implications in critically ill COVID-19 patients. MATERIALS AND METHODS: Retrospective, multi-center cohort study of hospitalized COVID-19 patients. Multivariate competing risk models were employed to explore the rate of reintubation and its determining factors. RESULTS: Two hundred eighty-one extubated patients were included (mean age, 61.0 years [±13.9]; 54.8% male). Reintubation occurred in 93 (33.1%). In multivariate analysis accounting for death, reintubation risk increased with age (hazard ratio [HR] 1.04 per 1-year increase, 95% confidence interval [CI] 1.02 -1.06), vasopressors (HR 1.84, 95% CI 1.04-3.60), renal replacement (HR 2.01, 95% CI 1.22-3.29), maximum PEEP (HR 1.07 per 1-unit increase, 95% CI 1.02 -1.12), paralytics (HR 1.48, 95% CI 1.08-2.25) and requiring more than nasal cannula immediately post-extubation (HR 2.19, 95% CI 1.37-3.50). Reintubation was associated with higher mortality (36.6% vs 2.1%; P < 0.0001) and risk of inpatient death after adjusting for multiple factors (HR 23.2, 95% CI 6.45-83.33). Prone ventilation, corticosteroids, anticoagulation, remdesivir and tocilizumab did not impact the risk of reintubation or death. CONCLUSIONS: Up to 1 in 3 critically ill COVID-19 patients required reintubation. Older age, paralytics, high PEEP, need for greater respiratory support following extubation and non-pulmonary organ failure predicted reintubation. Extubation failure strongly predicted adverse outcomes.


Assuntos
Extubação , COVID-19 , Idoso , Estudos de Coortes , Estado Terminal/terapia , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
7.
EClinicalMedicine ; 68: 102413, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38273886

RESUMO

Background: Standardized, high-quality PRO data reporting is crucial for patient centered care in the field of oncology, especially in clinical trials that establish standard of care. This study evaluated PRO endpoint design, conduct and reporting methods in FDA approved drugs for GU malignancies. Methods: A systematic review of the FDA archives identified GU cancer drug approvals from Feb 2007 to July 2022. ClinicalTrials.gov and PubMed were used to retrieve relevant data. PRO data was screened, and analytic tools, interpretation methods in the published papers and study protocols were reviewed. Compliance with PRO reporting standards were assessed using PRO Endpoint Analysis Score (PROEAS), a 24-point scoring scale from Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium (SISAQOL). Findings: We assessed 40 trial protocols with 27,011 participants, resulting in 14 renal cell cancer (RCC), 16 prostate cancer (PC), and 10 urothelial cancer (UC) approvals. PRO data was published for 27 trials, with 23 PRO publications (85%) focusing solely on PRO data, while 4 (15%) included PRO data in the original paper. Median time between primary clinical and secondary paper with PRO data was 10.5 months (range: 9-25 months). PROs were not planned as primary endpoints for any study but 14 (52%) reported them as secondary, 10 (37%) as exploratory outcomes, and 3 (11%) lacked any clarity on PRO data as endpoint. Mean PROEAS score of all GU cancers was 11.10 (range: 6-15), RCC (11.86, range: 6-15), UC (11.50, range: 9-14), and PC (10.56, range: 6-15). None met all the SISAQOL recommendations. Interpretation: Low overall PROEAS score and delays in PRO data publication in GU cancer drug trials conducted in the past decade emphasize the need for improvement in quality of design and conduct of PRO endpoint in future trials and accelerated publication of PRO endpoints, using standardized analysis, and prespecified hypothesis driven endpoint. These improvements are essential for facilitating interpretation and application of PRO study findings to define patient care. Funding: None.

8.
JCO Clin Cancer Inform ; 8: e2400044, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39058967

RESUMO

PURPOSE: Patients with advanced renal cell carcinoma (RCC) face significant challenges, stemming both from the complexities of the disease itself and the adverse effects of treatments. This study evaluated the feasibility and acceptability of a mobile health (mHealth) application tailored for education and symptom management of patients with advanced RCC receiving combined immune checkpoint inhibitor and tyrosine kinase inhibitor (ICI-TKI) therapy. METHODS: The primary end points were acceptability and feasibility. Acceptability was defined as the proportion of patients approached who consented to participate, setting a benchmark of at least 50% for this metric. Feasibility was gauged by the completion rate of the intervention among the participants; it required at least 50% of participants to fully complete the intervention and at least 70% to finish half of the administered questionnaires. The secondary end points included knowledge assessment and patient-reported outcomes (PROs). PROs were evaluated using validated instruments. To discern the changes between pre- and post-educational module quiz scores, we used the Wilcoxon signed-rank test. Time-course data of PROs were visualized using line plots and then compared using paired t-tests. RESULTS: From November 2022 to July 2023, 20 of 22 (90%) patients approached for the study consented and enrolled. Of the enrolled patients, 60% completed all questionnaires and knowledge assessments at every time point and 75% completed at least half of the surveys and questionnaires. Significant pre/post differences were noted in two of six quizzes in the knowledge assessment. This study population did not experience a significant change in PRO scores after starting therapy. CONCLUSION: The mHealth application designed for education and symptom management in patients with advanced RCC undergoing combination ICI-TKI has proven to be both acceptable and feasible, meeting previous research benchmarks.


Assuntos
Carcinoma de Células Renais , Estudos de Viabilidade , Inibidores de Checkpoint Imunológico , Neoplasias Renais , Aplicativos Móveis , Inibidores de Proteínas Quinases , Smartphone , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Masculino , Neoplasias Renais/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Educação de Pacientes como Assunto/métodos , Telemedicina , Adulto , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários
9.
Clin Lymphoma Myeloma Leuk ; 24(6): 400-406, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38429222

RESUMO

BACKGROUND: Hypomethylating agent + venetoclax is an effective frontline combination for acute myeloid leukemia, but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored. Outcomes have been poor for this population, with no standard treatment. PATIENTS AND METHODS: We retrospectively analyzed 72 Ven-naïve patients who received hypomethylating agents + venetoclax at relapse following alloHCT and aimed to evaluate the rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, CR/CRi duration, and overall survival. We leveraged our larger sample to analyze the impact of cytogenetic/molecular features on the odds of CR/CRi. RESULTS: CR/CRi was achieved among 32 of 67 (48%) patients, and MRD negativity was recorded among 10 of 12. NPM1 and IDH 1 or 2 mutations increased the odds of CR/CRi, as did increasing time from alloHCT to relapse. Fourteen patients subsequently received donor lymphocyte infusions or a second alloHCT. Responses lasted a median of 17.8 months (95% CI, 7.2 months to not reached), and responders had a greater median overall survival of 19.7 months (95% CI, 7.6-51.5 months) compared to 2.9 months among nonresponders (95% CI, 1.8-4.4 months; log-rank P < .01). Treatment was well tolerated, but prolonged cytopenias were common and most patients required reduction in the number of venetoclax days per cycle. CONCLUSION: These data support the efficacy of this combination in the alloHCT relapse setting where we report responses among nearly half of patients, with possibly greater benefit for NPM1 and IDH 1/2-mutated cases. These responses can be durable and profound as evidenced by conversion to MRD negativity.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Nucleofosmina , Sulfonamidas , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Masculino , Feminino , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Retrospectivos , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva
10.
Cancers (Basel) ; 16(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38275860

RESUMO

Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in the density of immune effector cells in node-negative tumors and a progressive rise in inhibitory immune players such as type 2 macrophages and upregulation of the PD-L1 checkpoint in men with N1 and N2-3 disease. There were no differences in immune cell densities with HPV status.

11.
J Natl Cancer Inst ; 116(6): 966-973, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38366627

RESUMO

INTRODUCTION: This study investigated the efficacy and safety of neoadjuvant chemotherapy for locally advance penile squamous cell carcinoma for which current evidence is lacking. METHODS: Included patients had locally advanced penile squamous cell carcinoma with clinical lymph node metastasis treated with at least 1 dose of neoadjuvant chemotherapy prior to planned consolidative lymphadenectomy. Objective response rates were assessed using Response Evaluation Criteria in Solid Tumors v1.1. The primary and secondary outcomes were overall survival and progression-free survival, estimated by the Kaplan-Meier method. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events v5.0. RESULTS: A total of 209 patients received neoadjuvant chemotherapy for locally advanced and clinically node-positive penile squamous cell carcinoma. The study population consisted of 7% of patients with stage II disease, 48% with stage III, and 45% with stage IV. Grade 2 treatment-related adverse events occurred in 35 (17%) patients, and no treatment-related mortality was observed. Of the patients, 201 (97%) completed planned consolidative lymphadenectomy. During follow-up, 106 (52.7%) patients expired, with a median overall survival of 37.0 months (95% confidence interval [CI] = 23.8 to 50.1 months) and median progression-free survival of 26.0 months (95% CI = 11.7 to 40.2 months). Objective response rate was 57.2%, with 87 (43.2%) having partial response and 28 (13.9%) having a complete response. Patients with objective response to neoadjuvant chemotherapy had a longer median overall survival (73.0 vs 17.0 months, P < .01) compared with those who did not. The lymph node pathologic complete response rate was 24.8% in the cohort. CONCLUSION: Neoadjuvant chemotherapy with lymphadenectomy for locally advanced penile squamous cell carcinoma is well tolerated and active to reduce the disease burden and improve long-term survival outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Escamosas , Excisão de Linfonodo , Terapia Neoadjuvante , Neoplasias Penianas , Humanos , Masculino , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/patologia , Neoplasias Penianas/mortalidade , Neoplasias Penianas/cirurgia , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Adulto , Estadiamento de Neoplasias , Metástase Linfática , Estudos Retrospectivos , Quimioterapia Adjuvante , Idoso de 80 Anos ou mais
12.
Cancers (Basel) ; 15(14)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37509374

RESUMO

PSCC is a rare cancer, with approximately half of all cases related to HPV. While HPV and p16 IHC testing have proven their prognostic value for oropharyngeal cancer, this is not yet established for PSCC. The current level of evidence exploring the relation between PSCC and HPV is moderate, so we conducted a systematic review following PRISMA guidelines to evaluate the prognostic role of HPV and p16 IHC in PSCC clinical outcomes. We searched the PubMed, Embase, and Cochrane databases and identified 34 relevant studies that met our inclusion criteria. Of these, 33 were retrospective cohort studies, and one was a cross-sectional study. Nine studies reported that HPV-positive and p16-positive PSCC had better overall survival (OS) and disease-free survival (DFS). This study highlights the need for a meta-analysis to determine the role of routine HPV status or p16 staining testing as part of the initial diagnosis and staging of PSCC patients worldwide.

13.
Cancers (Basel) ; 14(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35406500

RESUMO

Prostate cancer (PC) remains the most common malignancy and the second most common cause of cancer death in men. As a result of highly variable biological behavior and development of resistance to available agents under therapeutic pressure, optimal management is often unclear. Traditional surgical biopsies, even when augmented by genomic studies, may fail to provide adequate guidance for clinical decisions as these can only provide a snapshot of a dynamic process. Additionally, surgical biopsies are cumbersome to perform repeatedly and often involve risk. Liquid biopsies (LB) are defined as the analysis of either corpuscular (circulating tumor cells, extracellular vesicles) or molecular (circulating DNA or RNA) tumor-derived material. LB could more precisely identify clinically relevant alterations that characterize the metastatic potential of tumors, predict response to specific treatments or actively monitor for the emergence of resistance. These tests can potentially be repeated as often as deemed necessary and can detect real-time response to treatment with minimal inconvenience to the patient. In the current review, we consider common clinical scenarios to describe available LB assays in PC as a platform to explore existing evidence for their use in guiding decision making and to discuss current limitations to their adoption in the clinic.

14.
Cancers (Basel) ; 14(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36358643

RESUMO

Background: We hypothesize that cancer survival can be improved through adapting treatment strategies to cancer evolutionary dynamics and conducted a phase 1b study in metastatic castration sensitive prostate cancer (mCSPC). Methods: Men with asymptomatic mCSPC were enrolled and proceeded with a treatment break after achieving > 75% PSA decline with LHRH analog plus an NHA. ADT was restarted at the time of PSA or radiographic progression and held again after achieving >50% PSA decline. This on-off cycling of ADT continued until on treatment imaging progression. Results: At data cut off in August 2022, only 2 of the 16 evaluable patients were off study due to imaging progression at 28 months from first dose of LHRH analog for mCSPC. Two additional patients showed PSA progression at 12.4 and 20.5 months and remain on trial. Since none of the 16 patients developed imaging progression at 12 months, the study succeeded in its primary objective of feasibility. The secondary endpoints of median time to PSA progression and median time to radiographic progression have not been reached at a median follow up of 26 months. Conclusions: It is feasible to use an individual's PSA response and testosterone levels to guide intermittent ADT in mCSPC.

15.
iScience ; 25(5): 104322, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35502320

RESUMO

We compared three hospitalized patient cohorts and conducted mechanistic studies to determine if lipotoxicity worsens COVID-19. Cohort-1 (n = 30) compared COVID-19 patients dismissed home to those requiring intensive-care unit (ICU) transfer. Cohort-2 (n = 116) compared critically ill ICU patients with and without COVID-19. Cohort-3 (n = 3969) studied hypoalbuminemia and hypocalcemia's impact on COVID-19 mortality. Patients requiring ICU transfer had higher serum albumin unbound linoleic acid (LA). Unbound fatty acids and LA were elevated in ICU transfers, COVID-19 ICU patients and ICU non-survivors. COVID-19 ICU patients (cohort-2) had greater serum lipase, damage-associated molecular patterns (DAMPs), cytokines, hypocalcemia, hypoalbuminemia, organ failure and thrombotic events. Hypocalcemia and hypoalbuminemia independently associated with COVID-19 mortality in cohort-3. Experimentally, LA reacted with albumin, calcium and induced hypocalcemia, hypoalbuminemia in mice. Endothelial cells took up unbound LA, which depolarized their mitochondria. In mice, unbound LA increased DAMPs, cytokines, causing endothelial injury, organ failure and thrombosis. Therefore, excessive unbound LA in the circulation may worsen COVID-19 outcomes.

16.
TH Open ; 5(1): e73-e80, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33585788

RESUMO

Recognition of the adverse events of inferior vena cava filters (VCFs) has prompted the Food and Drug Administration (FDA) to issue safety warnings (2010 and 2014), advocating for removal, once the risk of pulmonary embolism has abated. Despite an initial increase in retrieval rates, these remain low (25-30% at 1 year in 2014). We retrospectively investigated retrieval trends in adults with VCFs placed between 2015 and 2018 at a single institution. The rate of retrievable VCF removal accounting for the competing risk of death was the main outcome. There were 494 VCFs placed (305 retrievable). The cumulative incidence of retrieval remained low (21% at 1 year), even after the second FDA warning (2014). Patients who resumed anticoagulation (AC) at any time were more likely to have retrieval (hazard ratio [HR] = 3.6, p < 0.01) and had higher retrieval rates at every time point (31.4 vs. 7.6% at 1 year). Advanced age (HR = 0.98 per year, p = 0.004), stroke (HR = 0.28, p = 0.028), and active malignancy (HR = 0.42, p = 0.006) predicted nonretrieval. Device-related complications were infrequent (<1%) but thrombotic complications occurred early and were more common for nonretrieved VCFs (17 vs. 12%, p = 0.29). Revision of guidelines to recommend active surveillance for the ability to tolerate AC in the immediate postimplantation period may improve retrieval rates.

17.
Open Heart ; 8(1)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34031215

RESUMO

OBJECTIVE: Bioprosthetic valve thrombosis (BPVT) is increasingly recognised as a major cause of prosthetic dysfunction in the first years postimplantation. How early abnormal gradients can be detected prior to diagnosis and how fast they normalise with anticoagulant therapy is unknown. We set forth to (1) evaluate patterns of increase in gradients prior to BPVT diagnosis and (2) characterise time-course of response to anticoagulation. METHODS: Patients treated with warfarin for BPVT (1999-2019) with clinically significant reduction of mean gradients (≥25%) were identified retrospectively. Recovery was defined as gradient decrease ≥50%, to postimplantation or to normal-range gradients per position, model and size. Time-to-BPVT (implantation-BPVT diagnosis), potential diagnostic delay (first abnormal gradient by position, model and size-BPVT diagnosis) and time-to-recovery (BPVT diagnosis-complete resolution) were recorded. RESULTS: 77 patients were identified; 32 (42%) aortic (23 surgical-12 porcine, 11 pericardial; 9 transcatheter); 24 (31%) mitral; 21 (27%) tricuspid. Median time-to-BPVT was 24, 21 and 10 months, respectively. Potential diagnostic delay was median 21 months for aortic, 4 months for mitral, but 0 for tricuspid. Recovery was significantly faster in mitral than aortic (median 2.5 vs 4.8 months, p=0.038) and tricuspid (median 5.9 months, p=0.025) positions. Porcine aortic valves responded faster than pericardial aortic valves (median 2.9 vs 20.3 months, p=0.004). CONCLUSION: Gradients start to increase months before the clinical BPVT diagnosis. Recovery is faster in mitral and surgical aortic porcine valves; a longer warfarin trial seems indicated in tricuspid and surgical aortic pericardial valves.


Assuntos
Bioprótese/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Diagnóstico Tardio , Cardiopatias/tratamento farmacológico , Próteses Valvulares Cardíacas/efeitos adversos , Trombose/tratamento farmacológico , Varfarina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Animais , Anticoagulantes/uso terapêutico , Ecocardiografia , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Humanos , Pessoa de Meia-Idade , Desenho de Prótese , Falha de Prótese , Estudos Retrospectivos , Suínos , Trombose/diagnóstico , Trombose/etiologia
18.
BMJ Case Rep ; 13(8)2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843450

RESUMO

Hypercalcaemia in malignancy is most commonly caused by paraneoplastic secretion of parathyroid hormone-related protein or osteolytic metastases. Very rarely (<1% of cases), the mechanism behind increased serum calcium is increased production of calcitriol (1,25-dihydroxyvitamin D) and even rarer is the occurrence of this phenomenon in solid malignancies, with few such instances reported in the literature. We present a case of a neuroendocrine malignancy originating in the oesophagus associated with calcitriol-induced hypercalcaemia, a phenomenon that has not been previously described. We review the pathophysiology of calcitriol-induced hypercalcaemia and previously reported cases of solid tumours with this presentation.


Assuntos
Calcitriol/biossíntese , Carcinoma Neuroendócrino/metabolismo , Neoplasias Esofágicas/metabolismo , Hipercalcemia/etiologia , Calcitriol/fisiologia , Carcinoma Neuroendócrino/secundário , Neoplasias Esofágicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade
19.
BMJ Case Rep ; 13(1)2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31900300

RESUMO

A 28-year-old primigravida was evaluated for complaints of difficulty urinating and pelvic pain of 6-weeks duration. She denied fever, night sweats, weight loss or fatigue. Pelvic ultrasonography revealed a single fetal pole with cardiac activity and a 7 cm mass in the anterior vagina which encased the urethra. The diagnosis of diffuse large B-cell lymphoma germinal centre type was made on analysis of biopsied pelvic mass. Whole body MRI revealed the disease was limited to the vagina. The patient received six cycles of Rituximab-cyclophosphamide, doxorubicin, vincristine and prednisone with significant improvement in her symptoms. Serial ultrasounds over the subsequent months showed appropriate development of the fetus. Whole body MRI after treatment showed decreased size and decreased signal of the primary pelvic mass compatible with favourable treatment response. Challenges in the management of this rare presentation of lymphoma are discussed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Neoplasias Vaginais/tratamento farmacológico , Adulto , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Disuria , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Imageamento por Ressonância Magnética , Dor Pélvica , Prednisona/uso terapêutico , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Rituximab/uso terapêutico , Ultrassonografia , Neoplasias Vaginais/diagnóstico por imagem , Vincristina/uso terapêutico
20.
TH Open ; 4(3): e263-e270, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32995704

RESUMO

A hypercoagulable state has been described in coronavirus disease 2019 (COVID-19) patients. Others have reported a survival advantage with prophylactic anticoagulation (pAC) and therapeutic anticoagulation (tAC), but these retrospective analyses have important limitations such as confounding by indication. We studied the impact of tAC and pAC compared with no anticoagulation (AC) on time to death in COVID-19. We performed a cross-sectional analysis of 127 deceased COVID-19 patients and compared time to death in those who received tAC ( n = 67), pAC ( n = 47), and no AC ( n = 13). Median time to death was longer with higher doses of AC (11 days for tAC, 8 days for pAC, and 4 days for no AC, p < 0.001). In multivariate analysis, AC was associated with longer time to death, both at prophylactic (hazard ratio [HR] = 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p < 0.001) and therapeutic doses (HR = 0.15; 95% CI: 0.07 to 0.32; p < 0.001) compared with no AC. Bleeding rates were similar among tAC and remaining patients (19 vs. 18%; p = 0.877). In deceased COVID-19 patients, AC was associated with a delay in death in a dose-dependent manner. Randomized trials are required to prospectively investigate the benefit and safety of higher doses of AC in this population.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA