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Sökning: WFRF:(Tewari AK)

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1.
  • Thomas, HS, et al. (författare)
  • 2019
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  • Glasbey, JC, et al. (författare)
  • 2021
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  • 2021
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  • 2021
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  • Bravo, L, et al. (författare)
  • 2021
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  • Tabiri, S, et al. (författare)
  • 2021
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  • Archer, M, et al. (författare)
  • Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease
  • 2021
  • Ingår i: Cell communication and signaling : CCS. - : Springer Science and Business Media LLC. - 1478-811X. ; 19:1, s. 78-
  • Tidskriftsartikel (refereegranskat)abstract
    • The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease.
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  • Chakravarty, D, et al. (författare)
  • Association between Incidental Pelvic Inflammation and Aggressive Prostate Cancer
  • 2022
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of pelvic inflammation on prostate cancer (PCa) biology and aggressive phenotype has never been studied. Our study objective was to evaluate the role of pelvic inflammation on PCa aggressiveness and its association with clinical outcomes in patients following radical prostatectomy (RP). This study has been conducted on a retrospective single-institutional consecutive cohort of 2278 patients who underwent robot-assisted laparoscopic prostatectomy (RALP) between 01/2013 and 10/2019. Data from 2085 patients were analyzed to study the association between pelvic inflammation and adverse pathology (AP), defined as Gleason Grade Group (GGG) > 2 and ≥ pT3 stage, at resection. In a subset of 1997 patients, the association between pelvic inflammation and biochemical recurrence (BCR) was studied. Alteration in tumor transcriptome and inflammatory markers in patients with and without pelvic inflammation were studied using microarray analysis, immunohistochemistry, and culture supernatants derived from inflamed sites used in functional assays. Changes in blood inflammatory markers in the study cohort were analyzed by O-link. In univariate analyses, pelvic inflammation emerged as a significant predictor of AP. Multivariate cox proportional-hazards regression analyses showed that high pelvic inflammation with pT3 stage and positive surgical margins significantly affected the time to BCR (p ≤ 0.05). PCa patients with high inflammation had elevated levels of pro-inflammatory cytokines in their tissues and in blood. Genes involved in epithelial-to-mesenchymal transition (EMT) and DNA damage response were upregulated in patients with pelvic inflammation. Attenuation of STAT and IL-6 signaling decreased tumor driving properties of conditioned medium from inflamed sites. Pelvic inflammation exacerbates the progression of prostate cancer and drives an aggressive phenotype.
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  • Chakravarty, D, et al. (författare)
  • Increased Hospitalization and Mortality from COVID-19 in Prostate Cancer Patients
  • 2021
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cancer patients with COVID-19 have a poor disease course. Among tumor types, prostate cancer and COVID-19 share several risk factors, and the interaction of prostate cancer and COVID-19 is purported to have an adverse outcome. Methods: This was a single-institution retrospective study on 286,609 patients who underwent the COVID-19 test at Mount Sinai Hospital system from March 2020 to December 2020. Chi-square/Fisher’s exact tests were used to summarize baseline characteristics of categorical data, and Mann–Whitney U test was used for continuous variables. Univariable logistic regression analysis to compare the hospitalization and mortality rates and the strength of association was obtained by the odds ratio and confidence interval. Results: This study aimed to compare hospitalization and mortality rates between men with COVID-19 and prostate cancer and those who were COVID-19-positive with non-prostate genitourinary malignancy or any solid cancer, and with breast cancer patients. We also compared our studies to others that reported the incidence and severity of COVID-19 in prostate cancer patients. Our studies highlight that patients with prostate cancer had higher susceptibility to COVID-19-related pathogenesis, resulting in higher mortality and hospitalization rates. Hospitalization and mortality rates were higher in prostate cancer patients with COVID-19 when compared with COVID-19 patients with non-prostate genitourinary (GU) malignancies.
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  • Dev, HS, et al. (författare)
  • Single-Site Surgery: More oR-LESS?
  • 2010
  • Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 58:6, s. 849-850
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Grover, S, et al. (författare)
  • Clinicopathological strategies to identify contralateral prostate cancer involvement in potential candidates for focal therapy
  • 2010
  • Ingår i: International journal of surgical pathology. - : SAGE Publications. - 1940-2465 .- 1066-8969. ; 18:6, s. 499-507
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To identify the magnitude and possible predictors of contralateral lobe involvement and contralateral extraprostatic extension (EPE) in prostatic biopsy—defined localized unilateral cancers. Patients and Methods: Between January 2005 and August 2009, 1861 patients underwent robotic-assisted radical prostatectomy at the authors’ institution. A total of 1114 had unilateral disease on preoperative biopsy. Final histopathology reports of these patients were reviewed. Results: Of the 1114 patients with unilateral disease on biopsy, 867 (77.9%) had contralateral or bilateral disease on final histopathology. EPE was found in 132 patients (11.9%). Twenty patients (1.8%) had contralateral EPE involvement. High-grade prostatic intraepithelial neoplasm (HGPIN) on biopsy was the significant predictor of contralateral lobe involvement on both univariate ( P = .02; odds ratio [OR] = 1.791) and multivariate analysis ( P = .004; OR = 2.677). Clinical stage T2 was the significant predictor of contralateral EPE on both univariate ( P = .012; OR = 5.250) and multivariate analysis ( P = .007; OR = 8.656). Conclusion: HGPIN on biopsy significantly predicts for contralateral lobe involvement and should be considered an exclusion criterion for focal therapy in prostate cancer patients. Patients with palpable tumor on digital rectal examination should be advised in favor of radical treatment as these patients may harbor more aggressive tumors involving the contralateral side despite the biopsy findings.
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  • Izadmehr, S, et al. (författare)
  • The Evolving Clinical Management of Genitourinary Cancers Amid the COVID-19 Pandemic
  • 2021
  • Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 11, s. 734963-
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronavirus disease–2019 (COVID-19), a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages throughout the world. There is a high incidence of infection and mortality among cancer patients with evidence to support that patients diagnosed with cancer and SARS-CoV-2 have an increased likelihood of a poor outcome. Clinically relevant changes imposed as a result of the pandemic, are either primary, due to changes in timing or therapeutic modality; or secondary, due to altered cooperative effects on disease progression or therapeutic outcomes. However, studies on the clinical management of patients with genitourinary cancers during the COVID-19 pandemic are limited and do little to differentiate primary or secondary impacts of COVID-19. Here, we provide a review of the epidemiology and biological consequences of SARS-CoV-2 infection in GU cancer patients as well as the impact of COVID-19 on the diagnosis and management of these patients, and the use and development of novel and innovative diagnostic tests, therapies, and technology. This article also discusses the biomedical advances to control the virus and evolving challenges in the management of prostate, bladder, kidney, testicular, and penile cancers at all stages of the patient journey during the first year of the COVID-19 pandemic.
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  • Izadmehr, S, et al. (författare)
  • The Evolving Clinical Management of Genitourinary Cancers Amid the COVID-19 Pandemic
  • 2021
  • Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 11, s. 734963-
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronavirus disease–2019 (COVID-19), a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages throughout the world. There is a high incidence of infection and mortality among cancer patients with evidence to support that patients diagnosed with cancer and SARS-CoV-2 have an increased likelihood of a poor outcome. Clinically relevant changes imposed as a result of the pandemic, are either primary, due to changes in timing or therapeutic modality; or secondary, due to altered cooperative effects on disease progression or therapeutic outcomes. However, studies on the clinical management of patients with genitourinary cancers during the COVID-19 pandemic are limited and do little to differentiate primary or secondary impacts of COVID-19. Here, we provide a review of the epidemiology and biological consequences of SARS-CoV-2 infection in GU cancer patients as well as the impact of COVID-19 on the diagnosis and management of these patients, and the use and development of novel and innovative diagnostic tests, therapies, and technology. This article also discusses the biomedical advances to control the virus and evolving challenges in the management of prostate, bladder, kidney, testicular, and penile cancers at all stages of the patient journey during the first year of the COVID-19 pandemic.
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  • Khatri, C, et al. (författare)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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  • Lundon, DJ, et al. (författare)
  • Social Determinants Predict Outcomes in Data From a Multi-Ethnic Cohort of 20,899 Patients Investigated for COVID-19
  • 2020
  • Ingår i: Frontiers in public health. - : Frontiers Media SA. - 2296-2565. ; 8, s. 571364-
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance:The COVID-19 pandemic exploits existing inequalities in social determinants of health (SDOH) in disease burden and access to healthcare. Few studies have examined these emerging disparities using indicators of SDOH.Objective:To evaluate predictors of COVID-19 test positivity, morbidity, and mortality and their implications for inequalities in SDOH and for future policies and health care improvements.Design, Setting, and Participants:A cross sectional analysis was performed on all patients tested for COVID-19 on the basis of symptoms with either a history of travel to at risk regions or close contact with a confirmed case, across the Mount Sinai Health System (MSHS) up until April 26th 2020.Main Outcomes and Measures:Primary outcome was death from COVID-19 and secondary outcomes were test positivity, and morbidity (e.g., hospitalization and intubation caused by COVID-19).Results:Of 20,899 tested patients, 8,928 tested positive, 1,701 were hospitalized, 684 were intubated, and 1,179 died from COVID-19. Age, sex, race/ethnicity, New York City borough (derived from first 3 digits of zip-code), and English as preferred language were significant predictors of test positivity, hospitalization, intubation and COVID-19 mortality following multivariable logistic regression analyses.Conclusions and Relevance:People residing in poorer boroughs were more likely to be burdened by and die from COVID-19. Our results highlight the importance of integrating comprehensive SDOH data into healthcare efforts with at-risk patient populations.
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