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1.
Dis Colon Rectum ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653496

RESUMO

BACKGROUND: Robotics has increased rates of minimally invasive surgery, with distinct advantages over open surgery. However, current commercially available robotic platforms have device and system issues that limit robot-assisted surgery expansion. OBJECTIVE: To demonstrate the safety and efficacy of a novel miniaturized robotic assisted surgery device in colectomy. DESIGN: Prospective, Investigational Device Exemption clinical study following the idea, development, exploration, assessment, and long-term follow-up (IDEAL) framework (Stage 2b, exploration). SETTINGS: Three centers with high-volume robotic colorectal cases and surgeons. PATIENTS: Patients scheduled for a right or left colectomy for benign or malignant disease. INTERVENTION: Colectomy with the novel miniaturized robotic assisted surgery device. MAIN OUTCOME MEASURES: For safety, intraoperative and device-related adverse events and 30-day morbidity. For efficacy, successful completion of pre-defined procedural steps without conversion. RESULTS: Thirty patients (13 female, 17 male) were analyzed. The mean age was 59.4 (SD 13.4) years. Seventy percent (n = 21) were overweight/obese and 53.3% (n = 16) had prior abdominal surgery. Forty percent had malignant and 60% benign disease. Cases were 15 right and 15 left colectomies. Overall operative time was median 146 (range, 80-309) minutes; 70 (range, 34-174) minutes was console time. There were no conversions to open surgery, and no intraoperative or device-related adverse events. In 100% (n = 30), the primary dissection was completed, and hemostasis maintained with the novel miniaturized robotic assisted surgery device. The morbidity rate was 26.7% minor and 3.3% major. The median length of stay was 2 days. There were no mortalities. LIMITATIONS: Single arm study, short-term follow-up. CONCLUSIONS: This first clinical study of a novel miniaturized robotic-assisted surgery device along the IDEAL framework demonstrated it was safe and effective. Given this success, further assessment and long-term follow-up of the miniaturized robotic assisted surgery device are planned for comparative clinical and economic effectiveness in colorectal surgery. See Video.

2.
Nanoscale Horiz ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597212

RESUMO

In recent years, extensive research efforts have been dedicated to the investigation of CdSe/CdS-based quantum-confined nanostructures, driven by their distinctive properties. The morphologies of these nanostructures have been shown to directly affect their properties, an area which has proven to be an important field of study. Herein, we report a new morphology of CdSe/CdS core-shell heterostructures in the form of a 'nanonail' - a modified nanorod-like morphology, in which a distinctive triangular head can be observed at one end of the structure. In-depth studies of this morphology reveal a material with tuneable rod length and width, as well as exceptional photoluminescent properties. Following this, we have demonstrated the ability to induce chiroptical activity via ligand exchange, revealing the important role of the specific morphology, shell thickness and chiral ligand concentration in the effect of ligand induced chirality. In addition, the cellular uptake and cytotoxicity of obtained chiral nanostructures were evaluated on human lung-derived A549 cancer cells, revealing a significant enantioselectivity in biological activity. Finally, analysis on monolayers of the material demonstrate the complete absence of FRET processes. Overall, this CdSe/CdS heterostructure is another tuneable morphology of a very important nanomaterial, one which shows great advantages and a range of potential applications.

3.
J Ultrasound ; 27(1): 173-177, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37751145

RESUMO

PURPOSE: The velamentous cord insertion is a rare pathology in which the umbilical blood vessels branch before reaching the placenta; by varying its structure, the cord becomes prone to spontaneous internal ruptures. This pathology is an obstetric emergency, so its early diagnosis is essential. METHODS AND RESULTS: We present a 27-year-old pregnant woman who attends an antenatal check-up for a routine third-trimester examination. Ultrasound reveals grade I polyhydramnios and suggestive findings of a trivascular umbilical cord with velamentous insertion 35 mm from the nearest placental border. The ultrasound diagnosis allowed a term delivery by elective cesarean section, avoiding severe complications of the maternal-fetal binomial. CONCLUSION: Velamentous cord insertion can and should have an early prenatal diagnosis, even from the second trimester, through imaging techniques such as transabdominal ultrasound or color Doppler. Early detection and appropriate peripartum management will highly reduce complications during labor.


Assuntos
Cesárea , Doenças Vasculares , Gravidez , Feminino , Humanos , Adulto , Placenta/diagnóstico por imagem , Diagnóstico Pré-Natal , Ultrassonografia , Ultrassonografia Pré-Natal
4.
Hum Vaccin Immunother ; 19(3): 2276629, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37947202

RESUMO

Renal cell carcinoma (RCC), especially clear cell RCC, is generally considered an immunotherapy-responsive cancer. Recently, the prognosis for patients with locally advanced and metastatic RCC has significantly improved with the regulatory approvals of anti-PD-1/PD-L1/CTLA-4 immune checkpoint inhibitor (ICI)-based regimens. Yet in most cases, RCC will remain initially unresponsive to treatment or will develop resistance over time. Hence, there remains an unmet need to understand what leads to ICI resistance and to develop novel immune and nonimmune treatments to enhance the response to ICIs. In this review, we highlight recently published studies and the latest clinical studies investigating the next generation of immune approaches to locally advanced and metastatic RCC beyond traditional ICIs. These trials include cytokines, gut microbiota-based therapies, novel immune checkpoint agents, vaccines, and chimeric antigen receptor T cells. These agents are being evaluated as monotherapy or in combination with traditional ICIs and will hopefully provide improved outcomes to patients with RCC soon.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/terapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Prognóstico , Imunoterapia , Neoplasias Renais/terapia
5.
Expert Rev Anticancer Ther ; 23(12): 1251-1263, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38030394

RESUMO

INTRODUCTION: Patients with metastatic prostate cancer, especially in the castrate-resistant setting, have a poor prognosis. Many agents have been approved for metastatic prostate cancer, such as androgen receptor pathway inhibitors, taxane-based chemotherapy, radiopharmaceuticals, and immunotherapy. However, prostate cancer remains the leading cause of cancer deaths in nonsmoking men. Fortunately, many more novel agents are under investigation. AREAS COVERED: We provide an overview of the broad group of novel therapies for metastatic prostate cancer, with an emphasis on active and recruiting clinical trials that have been recently published and/or presented at national or international meetings. EXPERT OPINION: The future for patients with metastatic prostate cancer is promising, with further development of novel therapies such as radiopharmaceuticals. Based on a growing understanding of prostate cancer biology, novel agents are being designed to overcome resistance to approved therapies. There are many trials using novel agents either as monotherapy or in combination with already approved agents with potential to further improve outcomes for men with advanced prostate cancer.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Compostos Radiofarmacêuticos , Neoplasias da Próstata/tratamento farmacológico , Imunoterapia , Antagonistas de Receptores de Andrógenos , Neoplasias de Próstata Resistentes à Castração/patologia
6.
J Natl Cancer Inst ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036464

RESUMO

BACKGROUND: This study examined real-world patients with locally advanced or metastatic urothelial carcinoma (advUC) considered ineligible for platinum-containing chemotherapy in the first-line (1 L) setting. METHODS: This retrospective observational study used data from a nationwide (US) de-identified patient-level electronic health record-derived database. Eligible adults (≥18 years) had an advUC diagnosis on or after January 1, 2016, and initiated 1 L systemic treatment ≥90 days before December 31, 2021. Platinum ineligibility was defined as ECOG performance status ≥3, creatinine clearance <30 mL/min, or ECOG performance status of 2 and creatinine clearance <45 mL/min. Overall survival (OS) and real-world progression-free survival (PFS) were summarized using the Kaplan-Meier method. RESULTS: The overall population comprised 4270 patients; 477 (11%) were considered platinum ineligible; 262 (55%) received a 1 L PD-1/PD-L1 immune checkpoint inhibitor and 118 (25%) received platinum-based chemotherapy. A total of 2335 patients (55%) were platinum eligible; 677 (29%) received a 1 L PD-1/PD-L1 inhibitor and 1229 (53%) received platinum-based chemotherapy. Median OS was 13.3 months (95% CI: 12.4-14.8) in platinum-eligible and 5.1 months (95% CI: 4.2-6.4) in platinum-ineligible patients. Median PFS was shorter in platinum-ineligible (3.4 months; 95% CI: 2.9-4.0) than platinum-eligible patients (5.9 months; 95% CI: 5.5-6.2) overall and when stratified by 1 L therapy type. CONCLUSION: This real-world study has shown for the first time the treatment patterns and outcomes in newly diagnosed patients with advUC ineligible for platinum-based chemotherapy. These findings provide quantitative benchmarks for platinum ineligibility in the 1 L advUC setting and highlight the need for novel therapy options.

7.
Artigo em Inglês | MEDLINE | ID: mdl-37884613

RESUMO

BACKGROUND: In patients with metastatic castration-resistant prostate cancer, darolutamide was well tolerated for 25 months, but minimal long-term safety data are available. METHODS: Treatment-emergent adverse events (TEAEs) for patients receiving darolutamide for a median of 38 months (n = 13) are described in this pooled analysis of individual patient data from phase 1/2 studies. RESULTS: All patients reported TEAEs (mostly grade 1/2). The most common TEAEs were diarrhea, abdominal pain, and nausea. Serious TEAEs were reported in six patients (none related to darolutamide). All treatment-related TEAEs (n = 5) were grade 1. CONCLUSIONS: Long-term darolutamide treatment was well tolerated; no new safety signals observed. In patients with mCRPC, long-term darolutamide treatment was well tolerated and no new safety signals were observed. These findings are consistent with previous reports, demonstrating a favorable safety and tolerability profile of darolutamide.

8.
Microbiol Spectr ; 11(6): e0276723, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37882559

RESUMO

IMPORTANCE: Respiration is a fundamental and complex process that bacteria use to produce energy. Despite aerobic respiration being the most common, some bacteria make use of a mode of respiration in the absence of oxygen, called anaerobic respiration, which can yield advantages in adaptation to various environmental conditions. Denitrification is part of this respiratory process ensuring higher respiratory flexibility under oxygen depletion. Here, we report for the first time the evidence of anaerobic growth of Brucella spp. under denitrifying conditions, which implies that this genus should be reconsidered as facultative anaerobic. Our study further describes that efficient denitrification is not equally found within the Brucella genus, with atypical species showing a greater ability to denitrify, correlated with higher expression of the genes involved, as compared to classical species.


Assuntos
Bactérias Anaeróbias , Bactérias , Bactérias Anaeróbias/metabolismo , Bactérias/metabolismo , Oxigênio/metabolismo
9.
JCO Precis Oncol ; 7: e2300131, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37467457

RESUMO

PURPOSE: Circulating tumor DNA (ctDNA) detection in blood has emerged as a prognostic and predictive biomarker demonstrating improved assessment of treatment response in patients receiving immune checkpoint inhibitors (ICIs). Here, we performed a pilot study to support the role of ctDNA for longitudinal treatment response monitoring in patients with advanced genitourinary (GU) malignancies receiving ICIs. MATERIALS AND METHODS: Patients with histologically confirmed advanced GU malignancies were prospectively enrolled. All eligible patients received ICI treatment for at least 12 weeks, followed by serial collection of blood samples every 6-8 weeks and conventional scans approximately every 12 weeks until disease progression. ctDNA analysis was performed using Signatera, a tumor-informed multiplex-polymerase chain reaction next-generation sequencing assay. Overall, the objective response rate (ORR) was reported and its association with ctDNA status was evaluated. Concordance rate between ctDNA dynamics and conventional imaging was also assessed. RESULTS: ctDNA analysis was performed on 98 banked plasma samples from 20 patients (15 renal, four urothelial, and one prostate). The median follow-up from the time of initiation of ICI to progressive disease (PD) or data cutoff was 67.7 weeks (range, 19.6-169.6). The ORR was 70% (14/20). Eight patients ultimately developed PD. The overall concordance between ctDNA dynamics and radiographic response was observed in 83% (15/18) of patients. Among the three patients with discordant results, two developed CNS metastases and one progressed with extracranial systemic disease while ctDNA remained undetectable. CONCLUSION: In this pilot study, longitudinal ctDNA analysis for monitoring response to ICI in patients with advanced GU tumors was feasible. Larger prospective studies are warranted to validate the utility of ctDNA as an ICI response monitoring tool in patients with advanced GU malignancies.


Assuntos
DNA Tumoral Circulante , Neoplasias , Neoplasias Urogenitais , Masculino , Humanos , DNA Tumoral Circulante/genética , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Projetos Piloto , Neoplasias Urogenitais/tratamento farmacológico , Neoplasias Urogenitais/genética
10.
Prostate ; 83(13): 1263-1269, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37301735

RESUMO

BACKGROUND: Differences in DNA alterations in prostate cancer among White, Black, and Asian men have been widely described. This is the first description of the frequency of DNA alterations in primary and metastatic prostate cancer samples of self-reported Hispanic men. METHODS: We utilized targeted next-generation sequencing tumor genomic profiles from prostate cancer tissues that underwent clinical sequencing at academic centers (GENIE 11th). We decided to restrict our analysis to the samples from Memorial Sloan Kettering Cancer Center as it was by far the main contributor of Hispanic samples. The numbers of men by self-reported ethnicity and racial categories were analyzed via Fisher's exact test between Hispanic-White versus non-Hispanic White. RESULTS AND LIMITATIONS: Our cohort consisted of 1412 primary and 818 metastatic adenocarcinomas. In primary adenocarcinomas, TMPRSS2 and ERG gene alterations were less common in non-Hispanic White men than Hispanic White (31.86% vs. 51.28%, p = 0.0007, odds ratio [OR] = 0.44 [0.27-0.72] and 25.34% vs. 42.31%, p = 0.002, OR = 0.46 [0.28-0.76]). In metastatic tumors, KRAS and CCNE1 alterations were less prevalent in non-Hispanic White men (1.03% vs. 7.50%, p = 0.014, OR = 0.13 [0.03, 0.78] and 1.29% vs. 10.00%, p = 0.003, OR = 0.12 [0.03, 0.54]). No significant differences were found in actionable alterations and androgen receptor mutations between the groups. Due to the lack of clinical characteristics and genetic ancestry in this dataset, correlation with these could not be explored. CONCLUSION: DNA alteration frequencies in primary and metastatic prostate cancer tumors differ among Hispanic-White and non-Hispanic White men. Notably, we found no significant differences in the prevalence of actionable genetic alterations between the groups, suggesting that a significant number of Hispanic men could benefit from the development of targeted therapies.


Assuntos
Adenocarcinoma , Neoplasias da Próstata , Humanos , Masculino , Adenocarcinoma/genética , DNA , Mutação , Neoplasias da Próstata/genética , Hispânico ou Latino , Brancos
11.
Expert Rev Anticancer Ther ; 23(7): 731-744, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37194261

RESUMO

INTRODUCTION: Metastatic castrate resistant prostate cancer (mCPRC) remains an aggressive form of prostate cancer that no longer responds to traditional hormonal treatment alone. Despite the advent of novel anti-androgen medications, many patients continue to progress, and as a result, there is a growing need for additional treatment options. AREAS COVERED: Lutetium-177 (177Lu) - PSMA-617 has become one of the new frontline treatment options for refractory metastatic castrate resistant prostate cancer after the failure of novel anti-androgen therapy and chemotherapy. Lu-177 has been used in real-world prospective trials and is now becoming utilized in newer phase III clinical trials. Here, we present a comprehensive overview of the current literature, covering retrospective studies, prospective studies, and clinical trials that established Lutetium-177-PSMA-617 (177Lu-PSMA-617) for the treatment of mCRPC. EXPERT OPINION: 177Lu - PSMA-617 has been approved for treatment of mCRPC based on positive phase III studies. While this treatment is tolerable and effective, biomarkers are necessary to determine which patients will benefit. In the future, radioligand treatments will likely be utilized in earlier lines of therapy and potentially in combination with other prostate cancer treatments.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Radioisótopos , Antígeno Prostático Específico , Resultado do Tratamento
12.
Cancers (Basel) ; 15(5)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36900202

RESUMO

Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors' immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. Considering that immunotherapy has shown modest results in advanced prostate cancer to date, we review the biologic rationale and promising results of BiTE therapy in this clinical setting and discuss potential tumor-associated antigens that may be integrated into BiTE construct designs. Our review also aims to evaluate the advances of BiTE therapies in prostate cancer, illustrate the major obstacles and underlying limitations, and discuss directions for future research.

13.
J Urol ; 209(5): 882-889, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36795962

RESUMO

PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/patologia , Cistectomia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
15.
J Clin Oncol ; 41(4): 881-892, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36269935

RESUMO

PURPOSE: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS: Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. RESULTS: Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION: ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Antígeno Prostático Específico
16.
Artigo em Inglês | MEDLINE | ID: mdl-36518034

RESUMO

Precision medicine seeks to individualize the dose from the beginning of phar-macological therapy based on the characteristics of each patient, genes involved in the metabolic phenotype, ethnicity or miscegenation, with the purpose to minimize adverse effects and optimize drug efficacy. The objective was to re-view studies that describe the association of the CYP2D6 and CYP2C19 genes with the tricontinental and Latin American ancestry of Peruvians. A biblio-graphic search was carried out in PubMed/Medline and SciELO, with various descriptors in Spanish and English. The results of this review confirm that the ethnic origin of Peruvians is triconti-nental due to European (mainly Spanish), African and Asian migration, in addi-tion to Latin American migration, being 60.2% mixed, 25.8% Amerindian, 5.9% white, 3.6% African descent, 1.2% Chinese and Japanese descent, and 3.3% unspecified. Studies on CYP2C19*3, CYP2D6*2, *3 and *6 have been reported in Peruvians, and the frequency is similar to that studied in Ecuadori-ans and Colombians. The CYP2C19*3, CYP2D6*3, and CYP2D6*6 alleles found in Peruvians are common in Europeans, Africans, and Asians; while CYP2D6*4 in Africans and CYP2D6*2 related to Asians. In some studies, the ethnic/gene association has not been demonstrated; while others have shown a significant association, which is why further investigation is warranted. It is concluded that the studies on CYP2D6 and CYP2C19 genes associated with the tricontinental and Latin American ancestry of Peruvians are little, and ac-cording to what has been investigated, the CYP2C19*3, CYP2D6*2, *3, *4 and *6 alleles have more related to their ancestry.

17.
World J Urol ; 40(11): 2707-2715, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36169695

RESUMO

PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Terapia Neoadjuvante/métodos , Cisplatino/uso terapêutico , Carboplatina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Músculos , Estudos Retrospectivos , Gencitabina
19.
J Infect ; 85(4): 412-417, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35830908

RESUMO

BACKGROUND: Monkeypox is the most prevalent Orthopoxvirus zoonosis infection since the eradication of smallpox. The current multi-country outbreak involves five WHO regions affecting mainly Europe. Accurate clinical and virological aspects of the disease outside endemic areas are needed. METHODS: We performed an observational study of cases diagnosed in Madrid (Spain) (May/June 2022). Confirmation from vesicular lesions swabs, Orthopoxvirus real-time PCR, sequencing, phylogenetic analysis, and direct detection by Electron microscopy was performed. In addition, a structured epidemiological questionnaire was completed systematically to gather sociodemographic, clinical, and behavioral data from all confirmed cases. FINDINGS: We extracted data from 48 patients, all cisgender men. The median age was 35 years (IQR 29 - 44), and 87.5% were MSM. The most prevalent symptoms were the presence of vesicular-umbilicated and pseudo-pustular skin lesions (93.8%), asthenia (66.6%), and fever (52.1%). In addition, the location of the lesions in the genital or perianal area was related to the role in sexual intercourse (p<0.001). Sequencing analysis indicated the virus circulating in Spain belongs to the western African clade. Like the other European cases in the outbreak, the Spanish isolates are a direct descendant of viruses previously detected in Nigeria, the UK, Singapore, and Israel in 2017-2018. CONCLUSIONS: Monkeypox is an emerging infectious disease in Europe where community transmission is reported, mainly in MSM. The first symptom was skin lesions instead of classical fever and rash. The disease follows a self-limited course, and there have been no cases with a serious presentation or severe complications.


Assuntos
Minorias Sexuais e de Gênero , Adulto , Animais , Surtos de Doenças , Febre/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , /epidemiologia , Vírus da Varíola dos Macacos/genética , Filogenia , Espanha/epidemiologia
20.
Rev. méd. hondur ; 90(1): 36-43, ene.-jun. 2022. ilus, tab.
Artigo em Espanhol | LILACS, BIMENA | ID: biblio-1393213

RESUMO

Antecedentes: No conocemos datos sobre evaluación de pruebas inmunológicas para mejorar el diagnóstico de Giardia duodenalis y Cryptosporidium spp., agentes etiológicos de diarrea de importancia mundial, en Honduras. Objetivos: Comparar dos pruebas inmunológicas para el diagnóstico de Giardia y Cryptosporidium spp. con microscopía de rutina y determinar su aplicabilidad local. Métodos: Estudio descriptivo transversal. En 2013, 134 muestras de heces recibidas en el Servicio de Parasitología del Hospital Escuela (HE) y 67 muestras del Centro de Salud Alonso Suazo (CSAS) se analizaron con una Prueba Rápida Inmunocromatográfica (PDR). En 2019-2020, 60 muestras de heces del HE se analizaron con una prueba inmunoenzimática ELISA. El protocolo de rutina incluyó examen directo en solución salina y solución de Lugol, coloración tricrómica y coloración ácido resistente modificada (ARM) (HE) y examen directo en solución salina y solución de Lugol (CSAS). Resultados: Cada prueba inmunológica mostró mayor positividad que la microscopía: en 134 muestras del HE para Giardia (6.7% vs 4.5%) y Cryptosporidium (3.7% vs 0.7%), similar en 67 muestras del CSAS (14.9% vs 7.5% para Giardia; 0.7% para Cryptosporidium con la prueba inmunológica). De 60 muestras analizadas por ELISA en HE, 31.7% fue positiva por Giardia vs 18.3% en examen directo y 23.3% en coloración tricrómica; 6.7% positiva por Cryptosporidium spp. vs 3.3% por coloración ARM. Discusión: Pruebas inmunológicas aumentaron significativamente el diagnóstico de ambas parasitosis; sin embargo, publicaciones sobre pruebas similares ofrecieron resultados no concluyentes. Por costo elevado podrían reservarse para pacientes pediátricos, pacientes inmunocomprometidos en hospitales, complementando microscopía. Los laboratorios de salud deben fortalecer capacidad diagnóstica...(AU)


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Testes Imunológicos/métodos , Giardíase/parasitologia , Giardia lamblia/isolamento & purificação , Criptosporidiose/diagnóstico , Cryptosporidium/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Estudos Transversais , Giardíase/epidemiologia , Criptosporidiose/epidemiologia , Diarreia/parasitologia , Honduras/epidemiologia
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