Publications by authors named "Andrea D"

195 Publications

Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis.

Rheumatology (Oxford) 2021 Apr 28. Epub 2021 Apr 28.

Rheumatology Unit, Department of Medicine, University of Padova, Padua, Italy.

Aim: Whether immunosuppressive therapy (IS) may be safely withdrawn in lupus nephritis (LN) is still unclear. We assessed rate and predictors of flare after IS withdrawal in patients with LN in remission.

Methods: Patients with biopsy-proven LN treated with IS between 1980 and 2020 were considered. Remission was defined as normal serum creatinine, proteinuria <0.5 g/24h, inactive urine sediment, and no extra-renal SLE activity on stable immunosuppressive and/or antimalarial therapy and/or prednisone ≤5mg/day. IS discontinuation was defined as the complete withdrawal of immunosuppressants, flares according to SLEDAI Flare Index. Predictors of flare were analyzed by multivariate logistic regression analysis.

Results: Among 513 SLE patients included in our database, 270 had LN. Of them, 238 underwent renal biopsy and were treated with ISs. Eighty-three patients (34.8%) discontinued IS, 46 ± 30 months after remission achievement. During a mean±SD follow-up of 116.5 ± 78 months, 19 patients (22.8%) developed a flare (8/19 renal) and were re-treated; 14/19 (73.7%) re-achieved remission after restarting therapy. Patients treated with IS therapy for at least three years after remission achievement had the lowest risk of relapse (OR 0.284, 95% CI 0.093-0.867, p= 0.023). At multivariate analysis, antimalarial maintenance therapy (OR 0.194, 95%CI 0.038-0.978, p= 0.047), age at IS discontinuation (OR 0.93, 95%CI 0.868-0.997, p= 0.040), remission duration >3 years before IS discontinuation (OR 0.231, 95%CI 0.058-0.920, p= 0.038) were protective against disease flares.

Conclusions: Withdrawal of IS is feasible in LN patients in remission for at least 3 years and on antimalarial therapy. Patients who experience flares can re-achieve remission with an appropriate treatment.
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http://dx.doi.org/10.1093/rheumatology/keab373DOI Listing
April 2021

Enhanced triacylglycerol catabolism by Carboxylesterase 1 promotes aggressive colorectal carcinoma.

J Clin Invest 2021 Apr 20. Epub 2021 Apr 20.

Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.

The ability to adapt to low-nutrient microenvironments is essential for tumor-cell survival and progression in solid cancers, such as colorectal carcinoma (CRC). Signaling by the NF-κB transcription-factor pathway associates with advanced disease stages and shorter survival in CRC patients. NF-κB has been shown to drive tumor-promoting inflammation, cancer-cell survival and intestinal epithelial cell (IEC) dedifferentiation in mouse models of CRC. However, whether NF-κB affects the metabolic adaptations that fuel aggressive disease in CRC patients is unknown. Here, we identified carboxylesterase 1 (CES1) as an essential NF-κB-regulated lipase linking obesity-associated inflammation with fat metabolism and adaptation to energy stress in aggressive CRC. CES1 promoted CRC-cell survival via cell-autonomous mechanisms that fuel fatty-acid oxidation (FAO) and prevent the toxic build-up of triacylglycerols. We found that elevated CES1 expression correlated with worse outcomes in overweight CRC patients. Accordingly, NF-κB drove CES1 expression in CRC consensus molecular subtype (CMS)4, associated with obesity, stemness and inflammation. CES1 was also upregulated by gene amplifications of its transcriptional regulator, HNF4A, in CMS2 tumors, reinforcing its clinical relevance as a driver of CRC. This subtype-based distribution and unfavourable prognostic correlation distinguished CES1 from other intracellular triacylglycerol lipases and suggest CES1 could provide a route to treat aggressive CRC.
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http://dx.doi.org/10.1172/JCI137845DOI Listing
April 2021

Reply to Francesco Montorsi, Marco Bandini, and Andrea Necchi's Letter to the Editor re: Francesco Soria, Marco Moschini, David D'Andrea, et al. Comparative Effectiveness in Perioperative Outcomes of Robotic versus Open Radical Cystectomy: Results from a Multicenter Contemporary Retrospective Cohort Study. Eur Urol Focus 2020;6:1233-9.

Eur Urol Focus 2021 Apr 16. Epub 2021 Apr 16.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, Motol Hospital, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.

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http://dx.doi.org/10.1016/j.euf.2021.04.002DOI Listing
April 2021

Novel Classification for Upper Tract Urothelial Carcinoma to Better Risk-stratify Patients Eligible for Kidney-sparing Strategies: An International Collaborative Study.

Eur Urol Focus 2021 Mar 24. Epub 2021 Mar 24.

Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background: The European Association of Urology risk stratification dichotomizes patients with upper tract urothelial carcinoma (UTUC) into two risk categories.

Objective: To evaluate the predictive value of a new classification to better risk stratify patients eligible for kidney-sparing surgery (KSS).

Design, Setting, And Participants: This was a retrospective study including 1214 patients from 21 centers who underwent ureterorenoscopy (URS) with biopsy followed by radical nephroureterectomy (RNU) for nonmetastatic UTUC between 2000 and 2017.

Outcome Measurements And Statistical Analysis: A multivariate logistic regression analysis identified predictors of muscle invasion (≥pT2) at RNU. The Youden index was used to identify cutoff points.

Results And Limitations: A total of 811 patients (67%) were male and the median age was 71 yr (interquartile range 63-77). The presence of non-organ-confined disease on preoperative imaging (p < 0.0001), sessile tumor (p < 0.0001), hydronephrosis (p = 0.0003), high-grade cytology (p = 0.0043), or biopsy (p = 0.0174) and higher age at diagnosis (p = 0.029) were independently associated with ≥pT2 at RNU. Tumor size was significantly associated with ≥pT2 disease only in univariate analysis with a cutoff of 2 cm. Tumor size and all significant categorical variables defined the high-risk category. Tumor multifocality and a history of radical cystectomy help to dichotomize between low-risk and intermediate-risk categories. The odds ratio for muscle invasion were 5.5 (95% confidence interval [CI] 1.3-24.0; p = 0.023) for intermediate risk versus low risk, and 12.7 (95% CI 3.0-54.5; p = 0.0006) for high risk versus low risk. Limitations include the retrospective design and selection bias (all patients underwent RNU).

Conclusions: Patients with low-risk UTUC represent ideal candidates for KSS, while some patients with intermediate-risk UTUC may also be considered. This classification needs further prospective validation and may help stratification in clinical trial design.

Patient Summary: We investigated factors predicting stage 2 or greater cancer of the upper urinary tract at the time of surgery for ureter and kidney removal and designed a new risk stratification. Patients with low or intermediate risk may be eligible for kidney-sparing surgery with close follow-up. Our classification scheme needs further validation based on cancer outcomes.
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http://dx.doi.org/10.1016/j.euf.2021.03.018DOI Listing
March 2021

Prognostic effect of preoperative systemic immune-inflammation index in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma.

Minerva Urol Nephrol 2021 Mar 26. Epub 2021 Mar 26.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria -

Background: Identifying those of patients with metastatic renal cell carcinoma (mRCC) who are most likely to benefit from cytoreductive nephrectomy (CN) is challenging. We tested the association between preoperative value of systemic immune-inflammation index (SII) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.

Methods: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment SII cut-off value, we found 710 to have the maximum Youden index value. The overall population was therefore divided into two SII groups using this cut-off (low, <710 vs high, ≥710). Univariable and multivariable Cox regression analyses tested the association SII and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the SII was evaluated with decision curve analysis (DCA).

Results: Among 613 mRCC patients, 298 (49%) patients had a SII ≥ 710. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high preoperative serum SII was significantly associated with worse OS (HR: 1.28, 95%CI: 1.07-1.54, p=0.01) and CSS (HR: 1.29, 95%CI: 1.08-1.55, p=0.01). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, SII≥ 710 was associated with OS (HR: 1.25, 95%CI: 1.04-1.50, p=0.02) and CSS (HR: 1.26, 95%CI: 1.05-1.52, p=0.01). The addition of SII only slightly improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.637 vs C-index = 0.629). On DCA, the inclusion of SII did not improve the net-benefit of the prognostic model. On multivariable analyses, SII ≥ 710 remained independently associated with the worse OS and CSS in IMDC intermediate risk group (both: HR: 1.31, 95%CI: 1.02 - 1.67, p = 0.03). In the subgroup analyses based on the BMI, among patients with BMI ≥ 25, SII was significantly associated with OS (HR: 1.29, 95%CI: 1.04 - 1.61, p = 0.02) and CSS (HR: 1.31, 95%CI: 1.05 - 1.63, p = 0.02).

Conclusions: We found an independent association of high SII prior to CN with unfavorable clinical outcomes, particularly in patients with intermediate risk mRCC and patients with increased BMI. Despite these results, it does not seem to add any prognostic or clinical benefit beyond that obtained by currently available clinicopathologic characteristics as sole worker.
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http://dx.doi.org/10.23736/S2724-6051.21.04023-6DOI Listing
March 2021

Comparing oncological outcomes of laparoscopic vs open radical nephroureterectomy for the treatment of upper tract urothelial carcinoma: A propensity score-matched analysis.

Arab J Urol 2020 Sep 4;19(1):31-36. Epub 2020 Sep 4.

Department of Urology, Luzerner Kantonsspital, Luzern, Switzerland.

Objectives: To compare oncological outcomes of open (ORNU) and laparoscopic radical nephroureterectomy (LRNU) after controlling for preoperative patient-derived factors.

Patients And Methods: We evaluated a multi-institutional collaborative database composed of 3984 patients diagnosed with upper tract urothelial carcinoma (UTUC) treated with RNU between 2006 and 2018. To adjust for potential selection bias, propensity score matching adjusted for age, gender and American society Anesthesiology (ASA) score was performed with one ORNU patient matched to one LRNU patient. Uni- and multivariable Cox regression evaluating the risk of overall recurrence, cancer-specific mortality (CSM) and overall mortality (OM) in the overall population and after propensity matching were performed.

Results: In total, 3984 patients underwent RNU, of these 3227 (81%) patients were treated with ORNU and 757 (19%) patients with LRNU. Within a median follow-up of 62 months, 1276 recurrences, 844 CSMs and 1128 OMs were recorded. On multivariable analyses, the LRNU approach was associated with an increased risk of overall recurrence (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.03-1.54; = 0.02), but on the other hand LRNU was associated with a protective effect on CSM (HR 0.74, 95% CI 0.56-0.98; = 0.04). After propensity matching analyses adjusted for age, gender and ASA score, 757 patients treated with LRNU and 757 patients treated with ORNU were available for the analyses. On multivariable Cox regression, LRNU vs ORNU was not associated with any difference in overall recurrence ( = 0.08), CSM ( = 0.1) or OM ( = 0.9).

Conclusion: Our present data suggest that even if the type of approach to RNU was associated with different survival outcomes considering the overall population, this difference vanished when adjusted for potential confounders in propensity matching analyses. Therefore, we found that LRNU is not inferior to the ORNU approach for the treatment of UTUC.

Abbreviations: ASA: American Society of Anesthesiology; CIS: carcinoma ; CSM: cancer-specific mortality; HR: hazard ratio; IQR: interquartile range; LN: lymph node; LNI: lymph node invasion; LVI: lymphovascular invasion; OM: overall mortality; pT: pathological tumour stage; RCT: randomised controlled trial; (L)(O)RNU: (laparoscopic) (open) radical nephroureterectomy; UTUC: upper tract urothelial carcinoma.
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http://dx.doi.org/10.1080/2090598X.2020.1817720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954493PMC
September 2020

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma.

Transl Androl Urol 2021 Feb;10(2):609-619

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Background: Accurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.

Methods: mRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).

Results: Among 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16-58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26-1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27-1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23-1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24-1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16-1.99, P=0.002).

Conclusions: In our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.
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http://dx.doi.org/10.21037/tau-20-1101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947468PMC
February 2021

Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guérin immunotherapy for T1G3/HG bladder cancer.

World J Urol 2021 Mar 13. Epub 2021 Mar 13.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Purpose: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC).

Materials And Methods: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression.

Results: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55).

Conclusion: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.
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http://dx.doi.org/10.1007/s00345-021-03653-1DOI Listing
March 2021

A panel of systemic inflammatory response biomarkers for outcome prediction in patients treated with radical cystectomy for urothelial carcinoma.

BJU Int 2021 Mar 1. Epub 2021 Mar 1.

Department of Urology, Comprehensive Cancer Centre, Medical University of Vienna, Vienna, Austria.

Objectives: To determine the predictive and prognostic value of a panel of systemic inflammatory response (SIR) biomarkers relative to established clinicopathological variables in order to improve patient selection and facilitate more efficient delivery of peri-operative systemic therapy.

Materials And Methods: The preoperative serum levels of a panel of SIR biomarkers, including albumin-globulin ratio, neutrophil-lymphocyte ratio, De Ritis ratio, monocyte-lymphocyte ratio and modified Glasgow prognostic score were assessed in 4199 patients treated with radical cystectomy for clinically non-metastatic urothelial carcinoma of the bladder. Patients were randomly divided into a training and a testing cohort. A machine-learning-based variable selection approach (least absolute shrinkage and selection operator regression) was used for the fitting of several multivariable predictive and prognostic models. The outcomes of interest included prediction of upstaging to carcinoma invading bladder muscle (MIBC), lymph node involvement, pT3/4 disease, cancer-specific survival (CSS) and recurrence-free survival (RFS). The discriminatory ability of each model was either quantified by area under the receiver-operating curves or by the C-index. After validation and calibration of each model, a nomogram was created and decision-curve analysis was used to evaluate the clinical net benefit.

Results: For all outcome variables, at least one SIR biomarker was selected by the machine-learning process to be of high discriminative power during the fitting of the models. In the testing cohort, model performance evaluation for preoperative prediction of lymph node metastasis, ≥pT3 disease and upstaging to MIBC showed a 200-fold bootstrap-corrected area under the curve of 67.3%, 73% and 65.8%, respectively. For postoperative prognosis of CSS and RFS, a 200-fold bootstrap corrected C-index of 73.3% and 72.2%, respectively, was found. However, even the most predictive combinations of SIR biomarkers only marginally increased the discriminative ability of the respective model in comparison to established clinicopathological variables.

Conclusion: While our machine-learning approach for fitting of the models with the highest discriminative ability incorporated several previously validated SIR biomarkers, these failed to improve the discriminative ability of the models to a clinically meaningful degree. While the prognostic and predictive value of such cheap and readily available biomarkers warrants further evaluation in the age of immunotherapy, additional novel biomarkers are still needed to improve risk stratification.
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http://dx.doi.org/10.1111/bju.15379DOI Listing
March 2021

Prognostic role of the systemic immune-inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

Cancer Immunol Immunother 2021 Feb 16. Epub 2021 Feb 16.

Department of Urology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Purpose: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).

Materials And Methods: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS).

Results: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis.

Conclusions: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.
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http://dx.doi.org/10.1007/s00262-021-02884-wDOI Listing
February 2021

Further Understanding of Urokinase Plasminogen Activator Overexpression in Urothelial Bladder Cancer Progression, Clinical Outcomes and Potential Therapeutic Targets.

Onco Targets Ther 2021 13;14:315-324. Epub 2021 Jan 13.

Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.

Purpose: The Plasminogen Activation System (PAS) plays a role in tumor growth, invasion and metastasis and has been associated with oncological outcomes in urinary bladder carcinoma (UBC). The use of the different components of this system as molecular markers could improve our understanding of the heterogeneous behavior of UBC and might enable earlier disease detection, individual risk stratification, more accurate outcome prediction and be a rationale for new targeted therapies.

Methods: A comprehensive literature search including relevant articles up to October 2020 was performed using the MEDLINE/PubMed database.

Results: The components of the PAS axis are involved in tumor progression through their signaling processes during angiogenesis, cell migration, metastasis and adhesion. The body of evidence shows an association of PAS component overexpression with adverse pathological features and clinical outcome in UBC. Overexpressed PAS components correlate with a higher pathological tumor grade and advanced tumor stage. In non-muscle-invasive bladder cancer (NMIBC), the PAS components were associated with disease outcome while in muscle-invasive bladder cancer (MIBC), it was associated with disease outcome and pathological features. Possible therapeutic approaches in the PAS for the treatment of UBC have only been sparsely investigated in in vitro and in vivo studies. Intravesical plasminogen activator inhibitor 1 (PAI-1) instillation in animal models yielded interesting results and warrant further exploration in Phase II studies.

Conclusion: The overexpression of PAS components in UBC tumor tissue is associated with adverse pathological features and worse oncological outcomes. These findings are mainly based on preclinical studies and retrospective series, which requires further prospective studies to translate the PAS into clinically useful biomarkers and therapeutic targets.
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http://dx.doi.org/10.2147/OTT.S242248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814246PMC
January 2021

Prevalence estimates of dementia in older adults in rural Kilimanjaro 2009-2010 and 2018-2019: is there evidence of changing prevalence?

Int J Geriatr Psychiatry 2021 Jun 23;36(6):950-959. Epub 2021 Feb 23.

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Introduction: Although limited, existing epidemiological data on dementia in sub-Saharan Africa indicate that prevalence may be increasing; contrasting with recent decreases observed in high-income countries. We have previously reported the age-adjusted prevalence of dementia in rural Tanzania in 2009-2010 as 6.4% (95% confidence interval [CI] 4.9-7.9) in individuals aged ≥70 years. We aimed to repeat a community-based dementia prevalence study in the same setting to assess whether prevalence has changed.

Methods: This was a two-phase door-to-door community-based cross-sectional survey in Kilimanjaro, Tanzania. In Phase I, trained primary health workers screened all consenting individuals aged ≥60 years from 12 villages using previously validated, locally developed, tools (IDEA cognitive screen and IDEA-Instrumental Activities of Daily Living questionnaire). Screening was conducted using a mobile digital application (app) on a hand-held tablet. In Phase II, a stratified sample of those identified in Phase I were clinically assessed using the DSM-5 criteria and diagnoses subsequently confirmed by consensus panel.

Results: Of 3011 people who consented, 424 screened positive for probable dementia and 227 for possible dementia. During clinical assessment in Phase II, 105 individuals met DSM-5 dementia criteria. The age-adjusted prevalence of dementia was 4.6% (95% CI 2.9-6.4) in those aged ≥60 years and 8.9% (95% CI 6.1-11.8) in those aged ≥70 years. Prevalence rates increased significantly with age.

Conclusions: The prevalence of dementia in this rural Tanzanian population appears to have increased since 2010, although not significantly. Dementia is likely to become a significant health burden in this population as demographic transition continues.
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http://dx.doi.org/10.1002/gps.5498DOI Listing
June 2021

Identification of patients with metastatic castration-sensitive or metastatic castration-resistant prostate cancer using administrative health claims and laboratory data.

Curr Med Res Opin 2021 Apr 13;37(4):609-622. Epub 2021 Feb 13.

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.

Objective: To develop algorithms to identify metastatic castration-sensitive prostate cancer (mCSPC) patients and castration-resistant prostate cancer (mCRPC) patients, using health claims data and laboratory test results.

Methods: A targeted literature review summarized mCSPC and mCRPC patient selection criteria previously used in real-world retrospective studies. Novel algorithms to identify mCSPC and mCRPC were developed based on diagnosis codes indicating hormone sensitivity/resistance, prostate-specific antigen (PSA) test results, and claims for castration and mCRPC-specific treatments. These algorithms were applied to claims data from Optum Clinformatics Extended DataMart (Date of Death) Databases (commercial insurance/Medicare Advantage [COM/MA]; 01 January 2014-31 July 2019) and Medicare Fee-for-Service (Medicare-FFS; 01 January 2014-31 December 2017).

Results: Previous real-world studies identified mCSPC primarily based on metastasis diagnosis codes, and mCRPC based on mCRPC-specific drugs. Using the current study's algorithms, 7034 COM/MA and 19,981 Medicare-FFS patients were identified as having mCSPC, and 2578 COM/MA and 11,554 Medicare-FFS as having mCRPC. Most mCSPC patients were identified based on evidence of being hormone/castration-naive. Patients were identified as having mCRPC most commonly based on rising PSA (COM/MA), or at the metastasis diagnosis date if it occurred after castration (Medicare-FFS). Among patients with mCSPC, 14-17% had evidence of progression to castration resistance during a median 1-year follow-up period, mostly based on use of mCRPC-specific drugs.

Conclusions: Comprehensive algorithms based on claims and laboratory data were developed to identify and distinguish patients with mCSPC and mCRPC. This will facilitate appropriate identification of mCSPC and mCRPC patients based on health claims data and better understanding of patient unmet needs in real-world settings.
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http://dx.doi.org/10.1080/03007995.2021.1879753DOI Listing
April 2021

A comparison of perioperative outcomes of laparoscopic versus open nephroureterectomy for upper tract urothelial carcinoma: a propensity score matching analysis.

Minerva Urol Nefrol 2021 01 13. Epub 2021 Jan 13.

Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland.

Background: Radical nephroureterectomy (RNU) with the concomitant excision of the distal ureter and bladder cuff is the current standard of care for the treatment of muscle invasive and/or high-risk upper tract urothelial carcinoma (UTUC). In small uncontrolled studies, laparoscopic RNU has been suggested to be associated with better perioperative outcomes compared to open RNU. The aim of our study was to compare the perioperative oncological and functional outcomes of open RNU versus laparoscopic RNU after adjusting for preoperative baseline patient-related characteristics.

Methods: We evaluated a multi institutional retrospective database composed by 1512 patients diagnosed with UTUC and treated with open or laparoscopic RNU between 1990 and 2016. Perioperative outcomes included operative time, blood loss, and length of hospital stay, as well as postoperative complications, readmission, reoperation, and mortality rates at 30 and 90 days from surgery. A 1:1 propensity score matching estimated using logistic regression with the teffects psmatch function of STATA 13® (caliper 0.2, no replacement) was performed using preoperative parameters such as: age, gender, body mass index (BMI), and American Society of Anesthesiologists (ASA) score.

Results: Overall, 1007 (66.6%) patients were treated with open and 505 (33.4%) with laparoscopic RNU. Open RNU resulted into shorter median operative time (180 vs 230 min, p<0.001) and longer median hospital stay (10 vs 7 days, p<0.001) in comparison to laparoscopic RNU. No statistically significant difference was identified for the other variables of interest (all p>0.05). At multivariable linear regression after propensity score matching adjusted for lymph node dissection and year of surgery, laparoscopic RNU resulted in longer operative time (Coefficient 43.6, 95% CI 27.9-59.3, p<0.001) and shorter hospital stay (Coefficient -1.27, 95% CI -2.1 to -0.3, p=0.01) compared to open RNU, but the risk of other perioperative complications remained similar between the two treatments.

Conclusions: Laparoscopic RNU is associated with shorter hospital stay, but longer operative time in comparison to open RNU. Otherwise, there were no differences in other perioperative outcomes between these surgical modalities even after propensity score matching. The choice to offer laparoscopic or open RNU in the treatment of UTUC should not be based on concerns of different safety outcomes.
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http://dx.doi.org/10.23736/S0393-2249.20.04127-2DOI Listing
January 2021

Development of a brief screening method for identification of depression in older adults in Sub-Saharan Africa.

Aging Ment Health 2021 Jan 4:1-8. Epub 2021 Jan 4.

Clinical and Translational Medicine, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Objectives: To develop a brief, culturally appropriate screening tool for identifying late life depression (LLD), for use by non-specialist clinicians in primary and out-patient care settings in sub-Saharan Africa (SSA).

Background: Depressive disorders are a leading contributor to the global health burden. LLD is common and cases will increase as populations' age, particularly in low- and middle-income countries (LMICs), such as those in SSA. A chronic mental health workforce shortage and the absence of culturally adapted LLD screening tools to aid non-specialist clinicians have contributed to a significant diagnostic gap.

Design: A systematic random sample of older people attending general medical clinics were interviewed using a 30-item LLD questionnaire, developed utilizing a Delphi consensus analysis of items from the Geriatric Depression Scale, Patient Health Questionnaire-2 and questions developed from a study of lay conceptualisations of depression in Tanzania. The items were assessed for validity against blinded DSM 5 diagnosis of depression by a research doctor. Factor and item analysis were then used to refine the questionnaire.

Results: The 12-item Maddison Old-age Scale for Identifying Depression (MOSHI-D) was developed. It has good internal consistency (Cronbach's α = 0.820) and construct and criterion validity (AUROC = 0.880).

Conclusions: On initial evaluation, the MOSHI-D showed good internal validity. It should be easy for non-specialists to administer. External validation and further refinement will be conducted. A culturally-appropriate LLD screen may improve mental health care integration into existing healthcare settings within SSA and facilitate greater patient access to care, in accordance with current WHO strategy.
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http://dx.doi.org/10.1080/13607863.2020.1857696DOI Listing
January 2021

Preserving Well-being in Patients With Advanced and Late Prostate Cancer.

Urology 2020 Dec 26. Epub 2020 Dec 26.

Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

Androgen deprivation therapy, alone or in combination with androgen signaling inhibitors, is a treatment option for patients with advanced prostate cancer (PC). When making treatment decisions, health care providers must consider the long-term effects of treatment on the patient's overall health and well-being. Herein, we review the effects of these treatments on the musculoskeletal and cardiovascular systems, cognition, and fall risk, and provide management approaches for each. We also include an algorithm to help health care providers implement best clinical practices and interdisciplinary care for preserving the overall well-being of PC patients.
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http://dx.doi.org/10.1016/j.urology.2020.12.018DOI Listing
December 2020

The significance of De Ritis ratio in patients with radiation-recurrent prostate cancer undergoing salvage radical prostatectomy.

Arab J Urol 2020 May 31;18(4):213-218. Epub 2020 May 31.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Objective: To evaluate the clinical prognostic value of preoperative serum De Ritis ratio (DRR; aspartate aminotransferase/alanine aminotransferase) on postoperative survival outcomes in patients with radiation-recurrent prostate cancer (PCa) who underwent salvage radical prostatectomy (SRP).

Patients And Methods: A retrospective review was conducted of patients with radiation-recurrent PCa who underwent SRP in five tertiary referral centres from 2007 to 2015. An increased preoperative serum DRR was defined as ≥1.35. The association between DRR and postoperative outcomes was tested. Multivariate Cox analyses were performed to identify the independent predictors of biochemical recurrence (BCR), metastases-free survival (MFS), overall survival (OS), and cancer-specific survival (CSS).

Results: Overall 214 patients underwent SRP, of them 98 (45.8%) with a high serum DRR were included in the study. In a multivariate analysis high DRR was an independent predictor of BCR [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.16-2.78; = 0.009]. No significant association was found between preoperative DRR and MFS (HR 1.32, 95% CI 0.53-3.30; = 0.55), OS (HR 2.35, 95% CI 0.84-6.57; = 0.10), and CSS (HR 3.36, 95% CI 0.65-17.35; = 0.15).

Conclusion: Increased preoperative serum DRR is associated with the development of BCR in patients with radiation-recurrent PCa who underwent SRP. DRR might serve as an early indicator of BCR, which may facilitate recognition of potential relapse and could translate into more intense follow-up and even salvage therapy in selected patients.

Abbreviations: ADT: androgen-deprivation therapy; BCR, biochemical recurrence; BCRFS: BCR-free survival; CSS: cancer-specific survival; DRR: De Ritis ratio; HR: hazard ratio; MFS: metastasis-free survival; PCa: Prostate Cancer; OS: overall survival; PLND: pelvic lymph node dissection; (EB)RT: (external beam) radiotherapy; SRP: salvage radical prostatectomy.
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http://dx.doi.org/10.1080/2090598X.2020.1771947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717611PMC
May 2020

Phrenic Nerve Involvement in Neuralgic Amyotrophy (Parsonage-Turner Syndrome).

Sleep Med Clin 2020 Dec 5;15(4):539-543. Epub 2020 Oct 5.

Shirley Ryan AbilityLab, Feinberg School of Medicine, Northwestern University, 355 East Erie Street, 26N (Biologics), Chicago, IL 60611, USA. Electronic address:

Neuralgic amyotrophy is a poorly understood neuromuscular disorder affecting peripheral nerves mostly within the brachial plexus distribution but can also involve other sites including the phrenic nerve. In the classic form of the syndrome it causes proximal upper limb and neck pain on the affected side with subsequent muscle weakness that can be highly heterogeneous. Nocturnal noninvasive ventilation support is a first-line treatment after phrenic mononeuropathy. The regular monitoring of diaphragm function with spirometry and diaphragm ultrasound can help determine prognosis and inform decision-making.
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http://dx.doi.org/10.1016/j.jsmc.2020.08.002DOI Listing
December 2020

Pre-therapy serum albumin-to-globulin ratio in patients treated with neoadjuvant chemotherapy and radical nephroureterectomy for upper tract urothelial carcinoma.

World J Urol 2020 Oct 16. Epub 2020 Oct 16.

Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Purpose: The accurate selection of patients who are most likely to benefit from neoadjuvant chemotherapy is an important challenge in oncology. Serum AGR has been found to be associated with oncological outcomes in various malignancies. We assessed the association of pre-therapy serum albumin-to-globulin ratio (AGR) with pathologic response and oncological outcomes in patients treated with neoadjuvant platin-based chemotherapy followed by radical nephroureterectomy (RNU) for clinically non-metastatic UTUC.

Methods: We retrospectively included all clinically non-metastatic patients from a multicentric database who had neoadjuvant platin-based chemotherapy and RNU for UTUC. After assessing the pretreatment AGR cut-off value, we found 1.42 to have the maximum Youden index value. The overall population was therefore divided into two AGR groups using this cut-off (low, < 1.42 vs high, ≥ 1.42). A logistic regression was performed to measure the association with pathologic response after NAC. Univariable and multivariable Cox regression analyses tested the association of AGR with OS and RFS.

Results: Of 172 patients, 58 (34%) patients had an AGR < 1.42. Median follow-up was 26 (IQR 11-56) months. In logistic regression, low AGR was not associated with pathologic response. On univariable analyses, pre-therapy serum AGR was neither associated with OS HR 1.15 (95% CI 0.77-1.74; p = 0.47) nor RFS HR 1.48 (95% CI 0.98-1.22; p = 0.06). These results remained true regardless of the response to NAC.

Conclusion: Pre-therapy low serum AGR before NAC followed by RNU for clinically high-risk UTUC was not associated with pathological response or long-term oncological outcomes. Biomarkers that can complement clinical factors in UTUC are needed as clinical staging and risk stratification are still suboptimal leading to both over and under treatment despite the availability of effective therapies.
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http://dx.doi.org/10.1007/s00345-020-03479-3DOI Listing
October 2020

Diagnostic challenges and treatment strategies in the management of upper-tract urothelial carcinoma.

Turk J Urol 2021 Feb 9;47(Supp. 1):S33-S44. Epub 2020 Oct 9.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Upper-tract urothelial carcinoma (UTUC) is a rare disease, posing many challenges for the treating physician due to the lack of strong evidence-based recommendations. However, novel molecular discoveries and a better understanding of the clinical behavior of the disease lead to a continuous evolution of therapeutic landscape in UTUC. The aim of the review is to provide a comprehensive update of the current diagnostic modalities and treatment strategies in UTUC with a special focus on recent developments and challenges. A comprehensive literature search including relevant articles up to August 2020 was performed using the MEDLINE/PubMed database. Despite several technological improvements, accurate staging and outcome prediction remain major challenges and hamper appropriate risk stratification. Kidney-sparing surgery can be offered in low risk UTUC; however, physician and patient must be aware of the high rate of recurrence and risk of progression due to tumor biology and understaging. The value and efficacy of intracavitary therapy in patients with UTUC remains unclear due to the lack of high-quality data. In high-risk diseases, radical nephroureterectomy with bladder cuff excision and template lymph node dissection is the standard of care. Perioperative systemic chemotherapy is today accepted as a novel standard for advanced cancers. In metastatic or unresectable disease, the therapeutic landscape is rapidly changing due to several novel agents, such as checkpoint inhibitors. While several diagnostic and treatment challenges remain, progress in endoscopic technology and molecular knowledge have ushered a new age in personalized management of UTUC. Novel accurate molecular and imaging biomarkers are, however, still needed to guide decision making as tissue acquisition remains suboptimal. Next generation sequencing and novel agents are promising to rapidly improve patient outcomes.
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http://dx.doi.org/10.5152/tud.2020.20392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057353PMC
February 2021

The Performance of Tumor Size as Risk Stratification Parameter in Upper Tract Urothelial Carcinoma (UTUC).

Clin Genitourin Cancer 2020 Sep 18. Epub 2020 Sep 18.

Department of Urology, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. Electronic address:

Introduction: The objective of this study was to evaluate the performance of different tumor diameters for identifying ≥ pT2 upper tract urothelial carcinoma (UTUC) at radical nephroureterectomy.

Patients And Methods: This was a multi-institutional retrospective study that included 932 patients who underwent radical nephroureterectomy for nonmetastatic UTUC between 2000 and 2016. Tumor sizes were pathologically assessed and categorized into 4 groups: ≤ 1 cm, 1.1 to 2 cm, 2.1 to 3 cm, and > 3 cm. We performed logistic regression and decision-curve analyses.

Results: Overall, 45 (4.8%) patients had a tumor size ≤ 1 cm, 141 (15.1%) between 1.1 and 2 cm, 247 (26.5%) between 2.1 and 3 cm, and 499 (53.5%) > 3 cm. In preoperative predictive models that were adjusted for the effects of standard clinicopathologic features, tumor diameters > 2 cm (odds ratio, 2.38; 95% confidence interval, 1.70-3.32; P < .001) and > 3 cm (odds ratio, 1.81; 95% confidence interval, 1.38-2.38; P < .001) were independently associated with ≥ pT2 pathologic staging. The addition of the > 2-cm diameter cutoff improved the area under the curve of the model from 58.8% to 63.0%. Decision-curve analyses demonstrated a clinical net benefit of 0.09 and a net reduction of 8 per 100 patients.

Conclusion: The 2-cm cutoff appears to be most useful in identifying patients at risk of harboring ≥ pT2 UTUC. This confirms the current European Association of Urology guideline's risk stratification. Tumor size alone is not sufficient for optimal risk stratification, rather a constellation of features is needed to select the best candidate for kidney-sparing surgery.
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http://dx.doi.org/10.1016/j.clgc.2020.09.002DOI Listing
September 2020

Prediction of the Need for an Extended Lymphadenectomy at the Time of Radical Cystectomy in Patients with Bladder Cancer.

Eur Urol Focus 2020 Oct 2. Epub 2020 Oct 2.

Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.

Background: A prospective randomized trial (LEA AUO AB 25/02) found no survival benefit in extended compared with limited pelvic lymph node dissection (PLND) templates in bladder cancer (BCa) patients treated with radical cystectomy (RC). However, the rate of lymph node invasion (LNI) in the standard and extended templates was lower than estimated.

Objective: To assess the accuracy of preoperative clinical and pathological parameters to predict LNI and to develop a model to preoperatively select candidates for the extended PLND templates.

Design, Setting, And Participants: A total of 903 BCa patients treated at a single institution were retrospectively identified. The primary outcome was to identify preoperatively the risk of LNI to tailor the type of PLND. The extended PLND templates consisted in the removal of pelvic lymph nodes together with the common iliac, presacral, para-aortocaval, interaortocaval, and paracaval sites up to the inferior mesenteric artery.

Intervention: A total of 903 BCa patients were treated with RC and bilateral extended PLND templates.

Outcome Measurements And Statistical Analysis: Several models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses. A nomogram predicting LNI in the extended pattern was developed and validated internally.

Results And Limitations: Overall, 55 patients (6.1%) had LNI in the extended PLND templates at RC. The median number of nodes removed was 19 (interquartile range: 13-26). A model including age, clinical T stage, clinical node stage, lymphovascular invasion, and presence of carcinoma in situ at the last transurethral resection before RC was developed. The AUC of this model is 73%. Using a cutoff of 3%, 108 extended PLNDs (12%) would be spared and only two LNIs (3%) would be missed. The main limitations of our model are the retrospective nature of the data, lack of external validation, and low rate of LNI.

Conclusions: This is the first proposed model to predict LNI in the extended PLND templates. This model might help urologists identify which patients might benefit from an extended PLND at the time of RC, reserving a standard PLND for all the others.

Patient Summary: We developed the first nomogram to predict lymph node invasion (LNI) in the extended pelvic lymph node dissection templates in bladder cancer patients treated with radical cystectomy. The adoption of our model to identify candidates for the extended pelvic lymph node dissection templates could avoid up to 12% of these procedures at the cost of missing only 3% of patients with LNI.
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http://dx.doi.org/10.1016/j.euf.2020.09.009DOI Listing
October 2020

Incidence and outcome of salvage cystectomy after bladder sparing therapy for muscle invasive bladder cancer: a systematic review and meta-analysis.

World J Urol 2020 Sep 29. Epub 2020 Sep 29.

Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Objective: We conducted a systematic review and meta-analysis to assess the available literature regarding the surgical and oncologic outcomes of patients undergoing salvage radical cystectomy (SV-RC) for recurrence or failure of bladder sparing therapy (BST) for muscle-invasive bladder cancer (MIBC).

Methods: We searched MEDLINE (PubMed), EMBASE and Google Scholar databases in May 2020. We included all studies of patients with ≥ cT2N0/xM0 bladder cancer that were eligible for all treatment modalities at the time of treatment decision who underwent BST including radiotherapy (RTX). A meta-analysis was conducted to calculate the pooled rate of several variables associated with an increased need for SV-RC. Study quality and risk of bias were assessed using MINORS criteria.

Results: 73 studies comprising 9110 patients were eligible for the meta-analysis. Weighted mean follow-up time was 61.1 months (range 12-144). The pooled rate of non-response to BST and local recurrence after BST, the two primary reasons for SV-RC, was 15.5% and 28.7%, respectively. The pooled rate of SV-RC was 19.2% for studies with a follow-up longer than 5 years. Only three studies provided a thorough report of complication rates after SV-RC. The overall complication rate ranged between 67 and 72% with a 30-day mortality rate of 0-8.8%. The pooled rates of 5 and 10-year disease-free survival after SV-RC were 54.3% and 45.6%, respectively.

Conclusion: Approximately one-fifth of patients treated with BST with a curative intent eventually require SV-RC. This procedure carries a proportionally high rate of complications and is usually accompanied by an incontinent urinary diversion.
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http://dx.doi.org/10.1007/s00345-020-03436-0DOI Listing
September 2020

Re: Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma (the POUT Trial): A Phase 3, Open-label, Randomised Controlled Trial.

Eur Urol 2021 01 24;79(1):163-164. Epub 2020 Sep 24.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Department of Urology, University of Jordan, Amman, Jordan; European Association of Urology Research Foundation, Arnhem, The Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2020.08.015DOI Listing
January 2021

Comparative effectiveness of neoadjuvant chemotherapy in bladder and upper urinary tract urothelial carcinoma.

BJU Int 2021 May 14;127(5):528-537. Epub 2020 Oct 14.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Objective: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery.

Patients And Methods: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses.

Results: A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS.

Conclusions: Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.
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http://dx.doi.org/10.1111/bju.15253DOI Listing
May 2021

Effectiveness of App-Based Cognitive Screening for Dementia by Lay Health Workers in Low Resource Settings. A Validation and Feasibility Study in Rural Tanzania.

J Geriatr Psychiatry Neurol 2020 Sep 23:891988720957105. Epub 2020 Sep 23.

Newcastle University, Newcastle upon Tyne, United Kingdom.

Background: The majority of people with dementia live in low-and middle-income countries (LMICs). In sub-Saharan Africa (SSA) human-resource shortages in mental health and geriatric medicine are well recognized. Use of technological solutions may improve access to diagnosis. We aimed to assess the diagnostic accuracy of a brief dementia screening mobile application (app) for non-specialist workers in rural Tanzania against blinded gold-standard diagnosis of DSM-5 dementia. The app includes 2 previously-validated culturally appropriate low-literacy screening tools for cognitive (IDEA cognitive screen) and functional impairment (abbreviated IDEA-IADL questionnaire).

Methods: This was a 2-stage community-based door-to-door study. In Stage1, rural primary health workers approached all individuals aged ≥60 years for app-based dementia screening in 12 villages in Hai district, Kilimanjaro Tanzania.In Stage 2, a stratified sub-sample were clinically-assessed for dementia blind to app screening score. Assessment included clinical history, neurological and bedside cognitive assessment and collateral history.

Results: 3011 (of 3122 eligible) older people consented to screening. Of these, 610 were evaluated in Stage 2. For the IDEA cognitive screen, the area under the receiver operating characteristic (AUROC) curve was 0.79 (95% CI 0.74-0.83) for DSM-5 dementia diagnosis (sensitivity 84.8%, specificity 58.4%). For those 358 (44%) completing the full app, AUROC was 0.78 for combined cognitive and informant-reported functional assessment.

Conclusions: The pilot dementia screening app had good sensitivity but lacked specificity for dementia when administered by non-specialist rural community workers. This technological approach may be a promising way forward in low-resource settings, specialist onward referral may be prioritized.
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http://dx.doi.org/10.1177/0891988720957105DOI Listing
September 2020

Wirelessly controlled, bioresorbable drug delivery device with active valves that exploit electrochemically triggered crevice corrosion.

Sci Adv 2020 Aug 28;6(35):eabb1093. Epub 2020 Aug 28.

Weldon School of Biomedical Engineering and School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA.

Implantable drug release platforms that offer wirelessly programmable control over pharmacokinetics have potential in advanced treatment protocols for hormone imbalances, malignant cancers, diabetic conditions, and others. We present a system with this type of functionality in which the constituent materials undergo complete bioresorption to eliminate device load from the patient after completing the final stage of the release process. Here, bioresorbable polyanhydride reservoirs store drugs in defined reservoirs without leakage until wirelessly triggered valve structures open to allow release. These valves operate through an electrochemical mechanism of geometrically accelerated corrosion induced by passage of electrical current from a wireless, bioresorbable power-harvesting unit. Evaluations in cell cultures demonstrate the efficacy of this technology for the treatment of cancerous tissues by release of the drug doxorubicin. Complete in vivo studies of platforms with multiple, independently controlled release events in live-animal models illustrate capabilities for control of blood glucose levels by timed delivery of insulin.
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http://dx.doi.org/10.1126/sciadv.abb1093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455185PMC
August 2020

The actin modulator hMENA regulates GAS6-AXL axis and pro-tumor cancer/stromal cell cooperation.

EMBO Rep 2020 11 10;21(11):e50078. Epub 2020 Sep 10.

Tumor Immunology and Immunotherapy Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

The dynamic interplay between cancer cells and cancer-associated fibroblasts (CAFs) is regulated by multiple signaling pathways, which can lead to cancer progression and therapy resistance. We have previously demonstrated that hMENA, a member of the actin regulatory protein of Ena/VASP family, and its tissue-specific isoforms influence a number of intracellular signaling pathways related to cancer progression. Here, we report a novel function of hMENA/hMENAΔv6 isoforms in tumor-promoting CAFs and in the modulation of pro-tumoral cancer cell/CAF crosstalk via GAS6/AXL axis regulation. LC-MS/MS proteomic analysis reveals that CAFs that overexpress hMENAΔv6 secrete the AXL ligand GAS6, favoring the invasiveness of AXL-expressing pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) cells. Reciprocally, hMENA/hMENAΔv6 regulates AXL expression in tumor cells, thus sustaining GAS6-AXL axis, reported as crucial in EMT, immune evasion, and drug resistance. Clinically, we found that a high hMENA/GAS6/AXL gene expression signature is associated with a poor prognosis in PDAC and NSCLC. We propose that hMENA contributes to cancer progression through paracrine tumor-stroma crosstalk, with far-reaching prognostic and therapeutic implications for NSCLC and PDAC.
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http://dx.doi.org/10.15252/embr.202050078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645265PMC
November 2020

The association of cigarette smoking and pathological response to neoadjuvant platinum-based chemotherapy in patients undergoing treatment for urinary bladder cancer - A prospective European multicenter observational study of the EAU Young Academic Urologists (YAU) urothelial carcinoma working group.

Surg Oncol 2020 Sep 30;34:312-317. Epub 2020 Jun 30.

Department of Urology, University Medical Center Hamburg-Eppendorf, Germany. Electronic address:

Objective: To prospectively study the impact of smoking on pathological response to neoadjuvant chemotherapy (NAC) in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

Materials & Methods: We collected standard clinicopathological variables, including smoking status (never, former, current) in patients undergoing NAC and RC for UCB at 12 European tertiary care centers between 12/2013-12/2015. Clinicopathological variables were compared according to smoking status. Multivariable logistic regression models were built to assess the association of smoking status and a) complete (no residual disease), b) partial (residual, non-muscle invasive disease), c) no pathological response (residual muscle invasive or lymph node positive disease). Kaplan-Meier and Cox regression analyses were employed to study the impact of response to NAC on survival.

Results And Limitations: Our final cohort consisted of 167 NAC patients with a median follow-up of 15 months (interquartile range (IQR) 9-26 months) of whom 48 (29%), 69 (41%), and 50 (30%) where never, former, and current smokers, respectively. Smoking was significantly associated with advanced age (p = 0.013), worse ECOG performance status (p = 0.049), and decreased pathological response to NAC (p = 0.045). On multivariable logistic regression analyses, former and current smoking status was significantly associated with lower odds of complete pathological response (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.16-0.87, p = 0.023, and OR 0.34, 95% CI 0.13-0.85, p = 0.021), while current smoking status was significantly associated with a greater likelihood of no pathological response (OR 2.49, 95% CI 1.02-6.06, p = 0.045). Response to NAC was confirmed as powerful predictor of survival.

Conclusions: Smoking status is adversely associated with pathological response to NAC. Smokers should be informed about these adverse effects, counseled regarding smoking cessation, and possibly be considered for immunotherpeutics as they may be more effective in smokers.
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http://dx.doi.org/10.1016/j.suronc.2020.06.006DOI Listing
September 2020

A case of vasospastic angina. Vasospasm physiopathology: a new therapeutic role for ranolazine?

Monaldi Arch Chest Dis 2020 Aug 3;90(3). Epub 2020 Aug 3.

Complex Operative Unit of Cardiology, Intensive Unit Coronary Care, Hospital Centre San Giuseppe e Melorio, ASL Caserta.

We report the case of a 40-year-old man, transferred from another hospital to our ICU because of acute coronary syndrome. Coronarography did not show coronary stenosis. Twenty-four hours monitoring EKG allowed diagnosis of Prinzmetal angina and appropriate therapy was administered. Six months after discharge due recurrence of symptoms, ranolazine was added to therapy. After one year the patient is symptoms free.
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http://dx.doi.org/10.4081/monaldi.2020.1295DOI Listing
August 2020