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1.
Support Care Cancer ; 32(2): 93, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38193937

RESUMO

OBJECTIVES: Studies that focus on the feasibility of using erlotinib plus chemoradiation to treat locally advanced head and neck cancer have given hints of improved survival outcomes compared to chemoradiation alone. However, the influence of this treatment regimen on the quality of life of the patients has not been documented. We conducted a study of this triple combination and now have documented follow-up survival data as well as long-term quality of life (QoL) measures. METHODS: Three sets of QoL questionnaires were given to patients with a diagnosis of head and neck cancer at two time points, pre- and post-treatment, to assess differences in quality of life after receiving chemotherapy with intra-arterial (IA) cisplatin (150 mg/m2), concomitant radiation (70 Gy), and oral erlotinib (150 mg/day). Additionally, patients were followed for a total of 5 years. RESULTS: Treatment had a detrimental effect on appearance, taste, and saliva domain scores in their QoL questionnaires. Nonetheless, fewer patients reported pain and anxiety. SIGNIFICANCE OF RESULTS: The combination of erlotinib with chemoradiation produced similar adverse effects on the QoL scores of patients with head and neck cancer as compared to chemoradiation alone.


Assuntos
Neoplasias de Cabeça e Pescoço , Qualidade de Vida , Humanos , Cisplatino/efeitos adversos , Cloridrato de Erlotinib/efeitos adversos , Ansiedade , Neoplasias de Cabeça e Pescoço/terapia
2.
J Neurochem ; 156(4): 513-523, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33107040

RESUMO

We have previously demonstrated hippocampal hyperglutamatergic signaling occurs prior to plaque accumulation in AßPP/PS1 mice. Here, we evaluate 2-Amino-6-(trifluoromethoxy) benzothiazole (riluzole) as an early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to substantial Beta amyloid (Aß) plaque accumulation and cognitive decline. Male AßPP/PS1 mice, a model of progressive cerebral amyloidosis, were treated with riluzole from 2-6 months of age. Morris water maze, in vivo electrochemistry, and immunofluorescence were performed to assess cognition, glutamatergic neurotransmission, and pathology, respectively, at 12 months. Four months of prodromal riluzole treatment in AßPP/PS1 mice resulted in long-lasting procognitive effects and attenuated glutamatergic tone that was observed six months after discontinuing riluzole treatment. Riluzole-treated AßPP/PS1 mice had significant improvement in long-term memory compared to vehicle-treated AßPP/PS1 mice that was similar to normal aging C57BL/6J control mice. Furthermore, basal glutamate concentration and evoked-glutamate release levels, which were elevated in vehicle-treated AßPP/PS1 mice, were restored to levels observed in age-matched C57BL/6J mice in AßPP/PS1 mice receiving prodromal riluzole treatment. Aß plaque accumulation was not altered with riluzole treatment. This study supports that interventions targeting the glutamatergic system during the early stages of AD progression have long-term effects on disease outcome, and importantly may prevent cognitive decline. Our observations provide preclinical support for targeting glutamate neurotransmission in patients at risk for developing AD. Read the Editorial Highlight for this article on page 399.


Assuntos
Precursor de Proteína beta-Amiloide , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Ácido Glutâmico/metabolismo , Presenilina-1 , Riluzol/uso terapêutico , Precursor de Proteína beta-Amiloide/genética , Animais , Disfunção Cognitiva/genética , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Presenilina-1/genética , Riluzol/farmacologia
3.
World J Urol ; 39(10): 3807-3813, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33966128

RESUMO

OBJECTIVES: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment. METHODS: Eighteen patients were consented for the study, five of which were screen failures. Six doses of pembrolizumab were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated from the time of consent through 30 days following pembrolizumab treatment. Clinical activity was determined using cystoscopy and biopsy of suspicious lesions. RESULTS: Treatment-related adverse events included one grade 4 adverse event (AEs) (adrenal insufficiency). There were nine grade 3 AEs (chest discomfort, pulmonary embolism, arthritis, wrist edema, injection site reaction, bilateral wrist pain, cardiomyopathy, hypokalemia, urinary tract infection). There were 49 grade 1 and 30 grade 2 AEs (88% of AEs). Eleven patients finished the treatment, and two patients died during the study. Of 13 patients treated, nine patients (69%) had no evidence of disease at 3 months following BCG treatment. CONCLUSIONS: We report for the first time that combining BCG and pembrolizumab in treating HGNMIBC is safe allowing complete treatment of most patients. A phase III trial has opened to test the efficacy of this combination in HGNMIBC (KEYNOTE-676).


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravenosa , Administração Intravesical , Insuficiência Adrenal/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Artralgia/induzido quimicamente , Artrite/induzido quimicamente , Carcinoma de Células de Transição/patologia , Cardiomiopatias/induzido quimicamente , Dor no Peito/induzido quimicamente , Cistoscopia , Edema/induzido quimicamente , Feminino , Humanos , Hipopotassemia/induzido quimicamente , Reação no Local da Injeção , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Neoplasia Residual , Embolia Pulmonar/induzido quimicamente , Neoplasias da Bexiga Urinária/patologia , Infecções Urinárias/induzido quimicamente , Articulação do Punho
4.
J Low Genit Tract Dis ; 25(2): 106-112, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33631781

RESUMO

OBJECTIVES: The aims of the study were to identify unmet basic needs (BNs) among women referred to colposcopy, to assess patient acceptability/satisfaction with assistance from a navigator to address unmet BNs, and to estimate adherence to colposcopy. METHODS: Women were recruited between September 2017 and January 2019 from 2 academic colposcopy centers, one serving a rural and one an urban area. Basic needs were assessed by phone before colposcopy appointments and considered unmet if unlikely to resolve in 1 month. Colposcopy adherence prestudy and poststudy implementation was abstracted over 4-6 months from administrative records. After a lead-in phase of 25 patients at each site, a BN navigator was offered to new participants with 1 or more unmet BNs. Primary outcome was adherence to initial appointment. RESULTS: Among 100 women, 59% had 1 or more unmet BNs, with similar prevalence between urban and rural sites. Adherence to initial colposcopy was 83% overall, 72% at the rural clinic, and 94% at the urban clinic (p = .006). These adherence rates were improved from 4 months before study launch (30/59 [51%] rural clinic and 68/137 [50%] urban clinic). Although acceptability of BN navigation was greater than 96% and women felt that it helped them get to their colposcopy visit, having a navigator was not associated with adherence. Women reporting no unmet BNs had the lowest adherence compared with women with 1 or more unmet BNs, regardless of navigator assistance (p = .03). CONCLUSIONS: Disadvantaged women who need colposcopy have unmet BNs and value navigator assistance for initial appointments. However, when appointment scheduling includes telephone reminders and inquiring about BNs, a navigator may not add value.


Assuntos
Colposcopia/psicologia , Colposcopia/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Neoplasias do Colo do Útero/psicologia , Adulto , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/psicologia , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Projetos Piloto , Relações Profissional-Paciente , Estudos Prospectivos , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal
5.
BJU Int ; 125(6): 905-910, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31837098

RESUMO

OBJECTIVE: To examine the correlation between urinary and faecal microbial profiles and the different aspects of lower urinary tract symptoms (LUTS) in men, as there is accumulating evidence that variations in the human microbiota may promote different benign disease conditions. PATIENTS AND METHODS: We extracted total DNA from urine and faecal samples of a group of men, under an Institutional Review Board-approved protocol. At the same time, International Prostate Symptom Score (IPSS) data were collected. We then amplified the extracted DNA and sequenced it using bacterial 16S ribosomal RNA gene high-throughput next-generation sequencing platform, and analysed the microbial profiles for taxonomy to examine the correlation between the different operational taxonomy units (OTUs) and LUTS represented by the total IPSS, the different symptom levels of the IPSS (mild, moderate, and severe) and its subcomponents of storage, nocturia, voiding, and bother. RESULTS: We included 30 patients (60 samples; one urine and one faecal per patient). In all, 48 faecal OTUs showed a significant correlation with one or more of the IPSS components; 27 with nocturia, 19 with bother, 16 with storage symptoms, and nine with voiding symptoms. The most substantial negative (protective) correlation was between Lachnospiraceae Blautia, a bacteria that increases the availability of gut anxiolytic and antidepressant short-chain fatty acids, and bother (correlation coefficient 0.702; P = 0.001). The abundance of L. Blautia continued to have a protective correlation against LUTS when looking at the different levels of IPSS severity (moderate and severe vs mild, correlation coefficient 0.6132; P = 0.002). Ten unique urinary OTUs showed significant correlation with LUTS; eight with nocturia, one with bother, three with storage, and one with voiding, but no faecal OUT had more than a low correlation with the outcomes of interest in this study. CONCLUSIONS: Our prospective work finds a plausible correlation between L. Blautia and LUTS. Additional studies are needed to determine if the correlations found in the present research are applicable to the general population of patients affected by LUTS.


Assuntos
Bactérias , Fezes/microbiologia , Sintomas do Trato Urinário Inferior , Microbiota/genética , Urina/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/microbiologia , Masculino , Estudos Prospectivos , Hiperplasia Prostática
6.
Can J Urol ; 27(1): 10106-10117, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32065868

RESUMO

INTRODUCTION: The role of organized sleep in overall health and quality-of-life (QoL) is critical. Nocturia necessarily disrupts the normal sleep cycle and negatively impacts one's health, work productivity, and QoL. We investigated, for the first time in an exploratory pilot, the effectiveness of mirabegron for improving sleep disturbance and nocturia. MATERIALS AND METHODS: This was a prospective, open-label 12-week trial evaluating the efficacy of mirabegron in 34 men and women with disordered sleep and lower urinary tract symptoms (LUTS). Subjects received mirabegron 25 mg daily for 4 weeks, then increased to 50 mg. Subjects completed the Patient-Reported Outcome Measurement Information System Sleep Disturbance Short Form (PROMIS-SDSF), Jenkins Sleep Scale (JSS), International Prostate Symptom Score (IPSS), voiding diaries, and QoL questionnaires. RESULTS: PROMIS-SDSF scores decreased from 26.5 points to 19.3, representing a categorical improvement from clinically 'mild' to 'none to slight' sleep disturbance (p < 0.001). JSS scores also decreased from 14.1 to 8.3 (p < 0.001). IPSS decreased from 21.0 to 12.4, denoting a categorical improvement from 'severe' to 'moderate' LUTS (p < 0.001). Voiding diaries revealed 1.9 fewer voids per day (p < 0.01) and 0.8 fewer nighttime voids (p < 0.05). QoL improved from 0% in subjects who selected 'mostly satisfied,' 'pleased,' or 'delighted' to 29.6% at follow up. CONCLUSIONS: Mirabegron use improves nocturia and produces rapid, durable, and clinically significant improvement in sleep disturbance and LUTS in males and females with urinary symptoms associated with disordered sleep.


Assuntos
Acetanilidas/farmacologia , Acetanilidas/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Noctúria/tratamento farmacológico , Transtornos do Sono-Vigília/tratamento farmacológico , Sono/efeitos dos fármacos , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Idoso , Feminino , Humanos , Sintomas do Trato Urinário Inferior/complicações , Masculino , Pessoa de Meia-Idade , Noctúria/complicações , Estudos Prospectivos , Sono/fisiologia , Transtornos do Sono-Vigília/complicações , Resultado do Tratamento
7.
PLoS Genet ; 13(10): e1007074, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29069084

RESUMO

Heterochromatin contains a significant part of nuclear DNA. Little is known about the mechanisms that govern heterochromatic DNA stability. We show here that in the yeast Saccharomyces cerevisiae (i) DNA mismatch repair (MMR) is required for the maintenance of heterochromatic DNA stability, (ii) MutLα (Mlh1-Pms1 heterodimer), MutSα (Msh2-Msh6 heterodimer), MutSß (Msh2-Msh3 heterodimer), and Exo1 are involved in MMR at heterochromatin, (iii) Exo1-independent MMR at heterochromatin frequently leads to the formation of Pol ζ-dependent mutations, (iv) MMR cooperates with the proofreading activity of Pol ε and the histone acetyltransferase Rtt109 in the maintenance of heterochromatic DNA stability, (v) repair of base-base mismatches at heterochromatin is less efficient than repair of base-base mismatches at euchromatin, and (vi) the efficiency of repair of 1-nt insertion/deletion loops at heterochromatin is similar to the efficiency of repair of 1-nt insertion/deletion loops at euchromatin.


Assuntos
Reparo de Erro de Pareamento de DNA , DNA Fúngico/química , Heterocromatina , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Sequência de Bases , Dano ao DNA , DNA Fúngico/genética , Exodesoxirribonucleases/genética , Genes pol , Histona Acetiltransferases/genética , Proteínas MutL/genética , Proteína MutS de Ligação de DNA com Erro de Pareamento/genética , Homologia de Sequência
8.
Cancer Immunol Immunother ; 68(6): 991-997, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30997535

RESUMO

OBJECTIVES: Advanced age and female sex have been associated with worse outcomes in patients undergoing radical cystectomy for muscle-invasive bladder cancer. A reduced immune response has been implicated as a mechanism. The objective of our study was to analyze the expression patterns of various cellular proteins active in bladder cancer immune pathways, and assess the correlation between age, sex, and the expression of these immune markers. METHODS: We obtained surgical tissue samples from equally distributed male/female patients with/without lymph node metastasis who had undergone radical cystectomy for urothelial carcinoma (UC) of the bladder (n = 50). Immunohistochemistry (IHC) for CD3 (cluster of differentiation), CD4, CD8, CD56, LAG-3 (lymphocyte-activation gene), TIM-3 (T-cell immunoglobulin and mucin-domain), PD-1 (programmed death) and PD-L1 molecules was performed and scored by a single pathologist (high versus low). Spearman's correlation and Chi square tests investigated the association between age, sex, and IHC results. RESULTS: Mean age at surgery was 67 years (range 50-78 years); all patients were Caucasians. The following percent of patients scored high for a stain: 18% CD3, 10% CD4, 0% CD8, 0% CD56, 20% LAG-3, 4% TIM-3, 0% PD-1 and 0% PD-L1. There was no association between patients' age, sex, and the expression of any of the immune markers (p > 0.05 for all). CONCLUSIONS: The association between advanced age, female sex, and worse outcomes in bladder cancer may be independent of the immune pathways active in the disease that we examined in this study.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Linfócitos do Interstício Tumoral/metabolismo , Músculos/metabolismo , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Antígenos CD/biossíntese , Antígeno B7-H1/biossíntese , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Receptor de Morte Celular Programada 1/biossíntese , Transdução de Sinais/imunologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo
9.
BJU Int ; 123(3): 401-410, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30537407

RESUMO

In an effort to improve the quality of statistics in the clinical urology literature, statisticians at European Urology, The Journal of Urology, Urology and BJU International came together to develop a set of guidelines to address common errors of statistical analysis, reporting, and interpretation. Authors should 'break any of the guidelines if it makes scientific sense to do so', but would need to provide a clear justification. Adoption of the guidelines will in our view not only increase the quality of published papers in our journals but improve statistical knowledge in our field in general.


Assuntos
Pesquisa Biomédica/normas , Bioestatística , Fidelidade a Diretrizes , Publicações Periódicas como Assunto/normas , Urologia/estatística & dados numéricos , Pesquisa Biomédica/estatística & dados numéricos , Políticas Editoriais , Humanos , Publicações Periódicas como Assunto/estatística & dados numéricos , Pesquisadores
10.
J Neurooncol ; 141(3): 523-531, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30644009

RESUMO

PURPOSE: Fluorescence-guided surgery (FGS) with the use of 5-aminolevulinic acid (5-ALA) leads to more extensive resection of high-grade glioma (HGG) and longer overall survival (OS) of patients compared to conventional resection. The purpose of this study is to investigate the effect of 5-ALA dosages on residual tumor volume (RTV) and OS in patients with glioblastoma. METHODS: A retrospective cohort study for patients who participated in a phase I and II dose-escalation clinical trial on 5-ALA for resection of HGG. A total of 25 patients were found to have newly diagnosed glioblastoma on histology and enrolled in our study. Patients receiving low doses of 5-ALA (10-30 mg/kg) (n = 6) were compared to those receiving high doses (40-50 mg/kg) (n = 19). Pre- and post-operative contrast enhanced T1W MRI were evaluated with volumetric analysis. RESULTS: Median RTV was 0.69 cm3 and 0.00 cm3 in the low and high dose groups respectively (p = 0.975). A gross total resection (GTR) was more likely in the high dose group, though this was not statistically significant. No significant difference was found in median OS between the high and low dose groups (p = 0.6787). CONCLUSIONS: High doses of 5-ALA FGS are associated with less RTV and greater probability of GTR. 5-ALA dose was not associated with OS. Further studies with a larger patient cohort are warranted.


Assuntos
Ácido Aminolevulínico , Neoplasias Encefálicas/cirurgia , Corantes Fluorescentes , Glioblastoma/cirurgia , Imagem Óptica , Cirurgia Assistida por Computador , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Meios de Contraste , Relação Dose-Resposta a Droga , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasia Residual , Imagem Óptica/métodos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Pharmacogenet Genomics ; 27(7): 264-269, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28562428

RESUMO

BACKGROUND: Alterations in nuclear pore complex (NPC) genes have been previously associated with response to chemotherapy. Using agnostic exome sequencing, we envisioned that new alleles in NPC genes, predictive of sensitivity to platinum treatment, could be discovered. METHODS: Twenty-two platinum-sensitive and six platinum-resistant ovarian cancer patients were tested. Platinum sensitivity was defined as disease-free survival greater than 6 months. Next-generation sequencing of exomes was used to compare platinum-sensitive and platinum-resistant patients. Single nucleotide variants (SNVs) associated with platinum sensitivity in NPC genes (n=30 genes) were identified. RESULTS: SNVs in three NPC genes were associated with response to platinum on univariate analysis. SNV rs79419059 (10T>C) in Nucleoporin 107 (Nup107) was associated with platinum resistance (P=0.0061), whereas rs2302811 (3662-4A>G) in Nucleoporin 188 (Nup188) and rs77246077 (3420-67T>A) in Nucleoporin 214 (Nup214) were associated with platinum sensitivity (P=0.0483 and 0.0091, respectively). Controlling for other confounders, multivariate age-adjusted Cox proportional hazard analysis showed rs79419059 to be significantly associated with platinum resistance (odds ratio: 4.519, 95% confidence interval: 1.317-15.501, P=0.0457). CONCLUSION: We identified a variant in the 3'-UTR region Nup107 unique to sensitivity to platinum in ovarian cancer. With validation of this variant, it is possible that a new marker predictive of patient response may be identified.


Assuntos
Antineoplásicos/uso terapêutico , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade
14.
J Reprod Immunol ; 163: 104241, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38492533

RESUMO

Epithelial ovarian cancer (OC) is the deadliest female reproductive cancer; an estimated 13,270 women will die from OC in 2023. Platinum-based chemotherapy resistance mechanisms contribute to poor OC 5-year survival rates. Peripheral inflammation is linked to various disease states and we previously identified unique peritoneal microbial features predictive of OC. We hypothesized that unique peripheral immune profiles and peritoneal microbial features may be predictive of disease-free interval (time to recurrence) and response to chemotherapy in participants with OC. We also investigated self-rated health (SRH) scores in the context of peripheral inflammation as a potential screening tool for OC. Blood and peritoneal fluid were collected from participants with OC or a benign adnexal mass (BPM). Lymphocyte populations were analyzed using Fluorescence Activated Cell Sorting, serum cytokine levels were analyzed using the Human Th17 Magnetic Bead Panel assay and peritoneal fluid microbial features were analyzed using Next Generation Sequencing (NGS). Participants completed a standardized questionnaire on self-rated physical and emotional health. Participants were classified into three chemotherapy response categories: platinum-refractory, platinum-resistant or platinum-sensitive. A significant positive correlation was found between elevated inflammatory status on the day of surgery and longer disease-free interval. SRH measures did not correlate with immune status in participants with OC or a BPM. We identified a correlation between peritoneal microbial features and chemotherapy response. We conclude that immune dysbiosis may be useful in predicting OC recurrence. The immune findings reported here set the framework for additional studies utilizing immune profiles to predict platinum-based chemotherapy responsiveness in OC.


Assuntos
Disbiose , Humanos , Feminino , Pessoa de Meia-Idade , Disbiose/imunologia , Adulto , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Idoso , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/imunologia , Prognóstico , Microbiota/imunologia , Microbiota/efeitos dos fármacos , Citocinas/metabolismo , Citocinas/sangue , Líquido Ascítico/imunologia , Líquido Ascítico/microbiologia
15.
Clin Genitourin Cancer ; 22(3): 102059, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38554570

RESUMO

OBJECTIVE: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).


Assuntos
Anticorpos Monoclonais Humanizados , Vacina BCG , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Masculino , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Administração Intravesical , Pessoa de Meia-Idade , Feminino , Recidiva Local de Neoplasia/tratamento farmacológico , Seguimentos , Resultado do Tratamento , Urinálise , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Neoplasias não Músculo Invasivas da Bexiga
16.
J Int Med Res ; 51(6): 3000605231179317, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37389562

RESUMO

OBJECTIVE: Aldo-keto reductase family 1 member B10 (AKR1B10) is a protein that is produced and secreted by a significant number of breast cancers. However, a potential confounder to the use of AKR1B10 as a tumor marker is its elevation in patients given cytotoxic chemotherapy. We therefore conducted a prospective study to analyze AKR1B10 levels in patients with breast cancer receiving neoadjuvant cytotoxic chemotherapy. METHODS: The study enrolled 10 patients from November 2015 to July 2017. All patients had locally advanced, but non-metastatic, breast cancer, and they received neoadjuvant chemotherapy followed by surgery. Serum AKR1B10 levels and tumor imaging were assessed before, during, and after chemotherapy. RESULTS: No increase in serum AKR1B10 levels was noted in patients receiving chemotherapy whose levels were elevated at diagnosis. CONCLUSION: The findings are complex, but the overall data suggest that AKR1B10 is suitable as a tumor marker in patients with elevated levels at the time of diagnosis.


Assuntos
Membro B10 da Família 1 de alfa-Ceto Redutase , Neoplasias da Mama , Humanos , Feminino , Estudos Prospectivos , Neoplasias da Mama/tratamento farmacológico , Transporte Biológico , Biomarcadores Tumorais
17.
J Am Acad Orthop Surg ; 31(2): e107-e117, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36580056

RESUMO

INTRODUCTION: Perioperative cefazolin administration for total joint arthroplasty is a first-line antibiotic recommended by the American Academy of Orthopaedic Surgeons (AAOS) guidelines for the prevention of periprosthetic joint infections (PJIs). We aim to analyze the clinical viability of giving patients with a documented penicillin allergy (PA) a perioperative full-strength cefazolin "test dose" under anesthesia. METHODS: This is a retrospective chart review of 2,451 total joint arthroplasties from a high-volume arthroplasty orthopaedic surgeon over a 5-year period from January 2013 through December 2017. This surgeon routinely gave patients with a documented PA a full-strength cefazolin test dose while under anesthesia instead of administrating a second-line antibiotic. The primary outcomes examined were allergic reaction and postoperative infection. RESULTS: Cefazolin was given to 87.1% of all patients (1,990) and 46.0% of patients with a PA (143). The total rate of allergic reactions among all patients was 0.5% (11). Only one patient with a documented PA who received cefazolin had an allergic reaction. The reaction was not severe and did not require any additional treatment. In patients who had no reported allergies and received cefazolin, 0.3% (6) had an allergic reaction. There was no statistically significant difference in the rate of allergic reaction when comparing patients with and without a PA (P = 0.95). Patients receiving cefazolin had an overall PJI rate of 2.9% (57) versus those patients receiving antibiotics other than cefazolin who sustained a 5.5% PJI rate (16), which was statistically significant (P = 0.02). CONCLUSION: This study found that utilization of a full-strength test dose of cefazolin in patients with a documented PA is a feasible, safe, and effective way of increasing the rate of cefazolin administration and thus mitigating the risk of PJIs.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Artroplastia do Joelho , Hipersensibilidade a Drogas , Hipersensibilidade , Infecções Relacionadas à Prótese , Humanos , Cefazolina , Artroplastia do Joelho/efeitos adversos , Estudos Retrospectivos , Antibioticoprofilaxia , Antibacterianos , Penicilinas/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/prevenção & controle , Artrite Infecciosa/etiologia , Artrite Infecciosa/prevenção & controle , Hipersensibilidade/etiologia , Artroplastia de Quadril/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/tratamento farmacológico
18.
J Surg Educ ; 80(3): 476-482, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36435733

RESUMO

OBJECTIVE: In March 2020, COVID-19 was declared a pandemic by the World Health Organization. This led to the outright cancellation of away rotations and in person residency interviews for the class of 2021. This study aims to identify the geographic relationships in the orthopedic match and further explore COVID-19's effect on these geographic relationships. Furthermore, we aim to compare the home program match rates before and after COVID-19. SETTING: Southern Illinois University School of Medicine, Department of Orthopedic Surgery (tertiary, university-based). DESIGN AND PARTICIPANTS: Residency websites and social media sites were used to record basic residency information as well as each resident's year, matriculated medical school, and matriculated medical school geographic data. This information was used to evaluate the proportion of orthopedic residents from "home program" medical schools and evaluate the geographic relationship of matched orthopedic residents. 202 Orthopedic residencies were initially identified and 134 allopathic and nonmilitary residency programs met the inclusion criteria. In all, 3253 of the 3931 (82.7%) current U.S orthopedic residents were included in the analysis. RESULTS: In the 4 orthopedic surgery residency classes before the pandemic (2017-2020), 21.8% of residency slots were filled by home program students. During the pandemic match cycle (2021), this number jumped to 28.2% (p < 0.0006). The increase was observed consistently across residency subgroup analysis: class size, doximity rank, and doximity research rank. Correspondingly, there was a statistically significant increase from 34.7% (2017-2020) to 39.3% (2021) (p = 0.0318) in residencies matching with same state medical students. Regional trends stayed consistent. Our study showed that residency programs matched applicants who went to same region medical schools during the 2020 to 2021 cycle at nearly the exact same rate as they did pre-pandemic (63.6%, up from 63.3%). CONCLUSIONS: Our study demonstrates that despite widespread virtual away rotations and virtual open houses, residency programs showed an increased preference for their home program students. This trend was significant and widespread, highlighting the generalized nationwide hesitation of both residency programs and students on the virtual interview process.


Assuntos
COVID-19 , Internato e Residência , Procedimentos Ortopédicos , Ortopedia , Estudantes de Medicina , Humanos , COVID-19/epidemiologia , Ortopedia/educação , Procedimentos Ortopédicos/educação
19.
Cureus ; 14(10): e30752, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36457602

RESUMO

Introduction The impact of modifications in curriculum and clinical rotations made secondary to the COVID-19 pandemic on medical education has yet to be fully investigated. We observed differences in the types of patients seen by medical students that may have resulted from clinical disruptions due to the COVID-19 pandemic. We then evaluated what impact these disruptions had on the students' clinical competency. Methods We obtained patient logbooks of third-year medical students (M3) and fourth-year sub-interns (M4) from the first three emergency medicine (EM) rotation blocks of the 2019-2020 (Y19) and 2020-2021 (Y20) academic years. We then reviewed and categorized the chief complaints seen and procedures in which they participated. A robust t-test was used to detect differences in chief complaints and procedures. Finally, we looked for objective differences using the chi-square test in clinical performance between the class of 2021 (Class21) and the class of 2022 (Class22), as assessed by performance on our institution's clinical competency examination. Results Overall, students saw a 25.3% decrease in average number of patient encounters. Statistically significant decreased average numbers of infectious (-28.3%, p=0.013); musculoskeletal (-22.2%, p=0.018); gastrointestinal (GI) (-24.6%, p<0.01); genitourinary (GU) (-33.2%, p<0.01); head, eyes, ears, nose, throat (HEENT) (-31.1%, p<0.01); trauma (-33.0%, p<0.01); and respiratory (-45.4%, p<0.001) complaints were observed. Both M3s and M4s encountered significantly less GU (-25.6%, p=0.048; -41.7%, p=0.016) and trauma (-29.1%, p=0.023; -33.2%, p=0.032) complaints in Y20. M4s saw significantly less GI complaints (-42.6%, p<0.001) in Y20, whereas M3s encountered significantly less psychiatric and HEENT complaints (-30.3%, p=0.046; -34.6%, p=0.013). Both classes saw significantly less respiratory complaints in Y20 but more so for M4s (-65.3%, p<0.001) than for M3s (-27.9%, p=0.033). There were no significant differences in average number of procedures between years. We did not observe any differences in overall clinical performance between the two selected classes. While class of 2021 scored a significantly higher average on a case of fatigue (p=0.0004) and class of 2022 on a case of abdominal pain (p<0.0001), there were no significant differences in the primary chief complaints that would be attributed to COVID-19, such as dyspnea. Conclusion Modifications made to curricula and clinical rotations due to the COVID-19 pandemic led to students encountering less patients overall, with significant decreases in multiple chief complaint types compared to Y19 but no significant change in procedure numbers. Notably, there was no major impact seen on clinical competency providing a positive argument for considering innovative teaching and learning methods.

20.
Artigo em Inglês | MEDLINE | ID: mdl-35329094

RESUMO

BACKGROUND: Structural inequities, in part, undergird urban-rural differences in cancer care. The current study aims to understand the potential consequences of structural inequities on rural and urban cancer patients' access to and perceived importance of supportive cancer care resources. METHODS: We used data collected from November 2017 to May 2018 from a larger cross-sectional needs assessment about patients' support needs, use of services, and perceptions at a Midwestern United States cancer center. Oncology patients received a study packet during their outpatient clinic visit, and interested patients consented and completed the questionnaires. RESULTS: Among the sample of 326 patients, 27% of the sample was rural. In adjusted logistic regression models, rural patients were less likely to report using any secondary support services (15% vs. 27%; OR = 0.43, 95%CI [0.22, 0.85], p = 0.02) and less likely than urban counterparts to perceive secondary support services as very important (51% vs. 64%; OR = 0.57, 95%CI [0.33, 0.94], p = 0.03). CONCLUSION: Structural inequities likely have implications on the reduced access to and importance of supportive care services observed for rural cancer patients. To eliminate persistent urban-rural disparities in cancer care, rural residents must have programs and policies that address cancer care and structural inequities.


Assuntos
Neoplasias , População Rural , Estudos Transversais , Acessibilidade aos Serviços de Saúde , Humanos , Avaliação das Necessidades , Neoplasias/epidemiologia , Neoplasias/terapia , Inquéritos e Questionários , População Urbana
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