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Article ; Online: Management of Hyperphosphatemia in End-Stage Renal Disease: A New Paradigm.

Rastogi, Anjay / Bhatt, Nisha / Rossetti, Sandro / Beto, Judith

Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation

2020 Volume 31, Issue 1, Page(s) 21–34

Abstract: Bone and mineral metabolism becomes dysregulated with progression of chronic kidney disease (CKD), and increasing levels of parathyroid hormone serve as an adaptive response to maintain normal phosphorus and calcium levels. In end-stage renal disease, ... ...

Abstract	Bone and mineral metabolism becomes dysregulated with progression of chronic kidney disease (CKD), and increasing levels of parathyroid hormone serve as an adaptive response to maintain normal phosphorus and calcium levels. In end-stage renal disease, this response becomes maladaptive and high levels of phosphorus may occur. We summarize strategies to control hyperphosphatemia based on a systematic literature review of clinical trial and real-world observational data on phosphorus control in hemodialysis patients with CKD-mineral bone disorder (CKD-MBD). These studies suggest that current management options (diet and lifestyle changes; regular dialysis treatment; and use of phosphate binders, vitamin D, calcimimetics) have their own benefits and limitations with variable clinical outcomes. A more integrated approach to phosphorus control in dialysis patients may be necessary, incorporating measurement of multiple biomarkers of CKD-MBD pathophysiology (calcium, phosphorus, and parathyroid hormone) and correlation between diet adjustments and CKD-MBD drugs, which may facilitate improved patient management.
MeSH term(s)	Calcimimetic Agents/therapeutic use ; Chelating Agents/therapeutic use ; Diet/methods ; Humans ; Hyperphosphatemia/complications ; Hyperphosphatemia/therapy ; Kidney Failure, Chronic/complications ; Vitamin D/therapeutic use
Chemical Substances	Calcimimetic Agents ; Chelating Agents ; Vitamin D (1406-16-2)
Language	English
Publishing date	2020-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	1080003-7
ISSN	1532-8503 ; 1051-2276
ISSN (online)	1532-8503
ISSN	1051-2276
DOI	10.1053/j.jrn.2020.02.003
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Article: The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a

Passarelli, Anna / Ventriglia, Jole / Pisano, Carmela / Cecere, Sabrina Chiara / Napoli, Marilena Di / Rossetti, Sabrina / Tambaro, Rosa / Tarotto, Luca / Fiore, Francesco / Farolfi, Alberto / Bartoletti, Michele / Pignata, Sandro

Frontiers in oncology

2023 Volume 12, Page(s) 1088962

Abstract: Endometrial cancer (EC) is the most common gynecologic cancer in Europe and its prevalence is increasing. EC includes a biological and clinical heterogeneous group of tumors, usually classified as type I (endometrioid) or type II (non-endometrioid) based ...

Abstract	Endometrial cancer (EC) is the most common gynecologic cancer in Europe and its prevalence is increasing. EC includes a biological and clinical heterogeneous group of tumors, usually classified as type I (endometrioid) or type II (non-endometrioid) based on the histopathological characteristics. In 2013, a new molecular classification was proposed by The Cancer Genome Atlas (TCGA) based on the comprehensive molecular profiling of EC. Several molecular somatic alterations have been described in development and progression of EC. Using these molecular features, EC was reclassified into four subgroups: POLE ultra-mutated, MSI hypermutated, copy-number low, and copy-number high that correlate with the prognosis. To this regard, it is widely reported that EC has more frequent mutations in the phosphatidylinositol 3-kinase (PI3K) pathway signaling than any other tumor.
Language	English
Publishing date	2023-01-13
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.1088962
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Article ; Online: The role of immunotherapy treatment in non-clear cell renal cell carcinoma: An analysis of the literature.

Ventriglia, Jole / Passarelli, Anna / Pisano, Carmela / Cecere, Sabrina Chiara / Rossetti, Sabrina / Feroce, Florinda / Forte, Miriam / Casartelli, Chiara / Tambaro, Rosa / Pignata, Sandro / Perversi, Fabio / Di Napoli, Marilena

Critical reviews in oncology/hematology

2023 Volume 188, Page(s) 104036

Abstract: Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group representing 15-30% of renal tumors. They are mostly excluded from immunotherapy trials due to their rarity and worse prognosis. This, alongside nccRCC misdiagnosis/misclassification, ... ...

Abstract	Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group representing 15-30% of renal tumors. They are mostly excluded from immunotherapy trials due to their rarity and worse prognosis. This, alongside nccRCC misdiagnosis/misclassification, lack of immune-biomarker expression rate data, lack of homogeneous data reporting, the retrospective nature of many studies, small sample sizes, and the fact that high-grade evidence only stems from trials mostly addressing the clear cell subtype, result in poorly defined treatments. We thus reviewed available data from several clinical trials, retrospective studies, and meta-analyses on immunotherapy responses and their correlation with histological subtypes and prognostic biomarkers. The papillary and unclassified subtypes are the best candidate for immunotherapy, showing response rates up to ∼35%. Chromophobe cancers, on the other end, have mostly null response rates. Cancers with sarcomatoid features respond very well to immunotherapy, regardless of their histology. Available data for translocation, medullary, collecting duct, and other nccRCCs are inconclusive. Regarding PD-L1, its expression correlates with better responses, but its prognostic value remains to be determined due to small sample sizes hindering direct statistical comparisons. It is necessary to involve a larger number of nccRCC patients and centers in clinical trials and report tumor response rates and PD-(L)1 and other markers' expression rates divided by nccRCC subtypes and not just for the whole cohorts. This will allow us to collect more robust data to best identify patients who can benefit from immunotherapy and ultimately define the standard of treatment. AVAILABILITY OF DATA AND MATERIAL: N/A.
MeSH term(s)	Humans ; Carcinoma, Renal Cell/therapy ; Carcinoma, Renal Cell/drug therapy ; Retrospective Studies ; Kidney Neoplasms/drug therapy ; Prognosis ; Immunotherapy
Language	English
Publishing date	2023-05-30
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	605680-5
ISSN	1879-0461 ; 0737-9587 ; 1040-8428
ISSN (online)	1879-0461
ISSN	0737-9587 ; 1040-8428
DOI	10.1016/j.critrevonc.2023.104036
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Article: Unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection in Stage II non-seminomatous germ cell tumor: A tertiary care experience.

Franzese, Dario / Tufano, Antonio / Izzo, Alessandro / Muscariello, Raffaele / Grimaldi, Giovanni / Quarto, Giuseppe / Castaldo, Luigi / Rossetti, Sabrina / Pandolfo, Savio Domenico / Desicato, Sonia / Del Prete, Paola / Ferro, Matteo / Pignata, Sandro / Perdonà, Sisto

Asian journal of urology

2023 Volume 10, Issue 4, Page(s) 440–445

Abstract: Objective: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) represents an integral component of the management of patients with non-seminomatous germ cell tumor (NSGCT). Modified templates have been proposed to minimize the surgical ... ...

Abstract	Objective: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) represents an integral component of the management of patients with non-seminomatous germ cell tumor (NSGCT). Modified templates have been proposed to minimize the surgical morbidity of the procedure. Moreover, the implementation of robotic surgery in this setting has been explored. We report our experience with unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection (PC-rRPLND) for clinical Stages IIA and IIB NSGCTs. Methods: A retrospective single institution review was performed including 33 patients undergoing PC-rRPLND for Stages IIA and IIB NSGCTs between January 2015 and February 2019. Following orchiectomy, patients were scheduled for chemotherapy with three cycles of bleomycin-etoposide-cisplatin. Patients with a residual tumor of <5 cm and an ipsilateral metastatic disease on pre- and post-chemotherapy CT scans were eligible for a unilateral template in absence of rising tumor markers. Descriptive statistics were provided for demographics, clinical characteristics, intraoperative and postoperative parameters. Perioperative, oncological, and functional outcomes were recorded. Results: Overall, 7 (21.2%) patients exhibited necrosis or fibrosis; 14 (42.4%) had mature teratoma; and 12 (36.4%) had viable tumor at final histology. The median lymph node size at surgery was 25 (interquartile range [IQR] 21-36) mm. Median operative time was 180 (IQR 165-215) min and no major postoperative complications were observed. Anterograde ejaculation was preserved in 75.8% of patients. Median follow-up was 26 (IQR 19-30) months and a total of three recurrences were recorded. Conclusion: PC-rRPLND is a reliable and technically reproducible procedure with safe oncological outcomes and acceptable postoperative ejaculatory function in well selected patients with NSGCTs.
Language	English
Publishing date	2023-07-25
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2831144-9
ISSN	2214-3882
ISSN	2214-3882
DOI	10.1016/j.ajur.2023.05.002
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Article: Clinical outcomes of volume of disease on patients receiving enzalutamide

Nuzzo, Pier Vitale / Ravera, Francesco / Saieva, Calogero / Zanardi, Elisa / Fotia, Giuseppe / Malgeri, Andrea / Rossetti, Sabrina / Valença, Loana Bueno / Oliveira, Thiago Martins / Vauchier, Charles / Pereira Mestre, Ricardo / Modesti, Mikol / Patrikidou, Anna / Pignata, Sandro / Procopio, Giuseppe / Fornarini, Giuseppe / De Giorgi, Ugo / Russo, Antonio / Francini, Edoardo

Therapeutic advances in medical oncology

2023 Volume 15, Page(s) 17588359231156147

Abstract: Background: Androgen receptor signaling inhibitors (ARSis) abiraterone acetate (AA) plus prednisone and enzalutamide (Enza), are currently the most administered first-line treatments for metastatic castration-resistant prostate cancer (mCRPC). AA and ... ...

Abstract	Background: Androgen receptor signaling inhibitors (ARSis) abiraterone acetate (AA) plus prednisone and enzalutamide (Enza), are currently the most administered first-line treatments for metastatic castration-resistant prostate cancer (mCRPC). AA and Enza have shown similar overall survival (OS) benefits and there is no consensus upon the best option for mCRPC first-line treatment. Volume of disease may represent a useful biomarker to predict response to therapy in such patients. Objectives: In this study, we seek to evaluate the impact of volume of disease on patients treated with first-line AA Design and methods: We retrospectively evaluated a cohort of consecutive patients with mCRPC categorized by volume of disease [high volume (HV) or low volume (LV) per E3805 criteria] at ARSi onset and treatment type (AA or Enza), assessing OS and radiographic progression-free survival (rPFS), from therapy start, as co-primary endpoints. Results: Of the 420 patients selected, 170 (40.5%) had LV and received AA (LV/AA), 76 (18.1%) LV and had Enza (LV/Enza), 124 (29.5%) HV and were given AA (HV/AA), and 50 (11.9%) HV and received Enza (HV/Enza). Among patients with LV, OS was significantly longer when treated with Enza [57.2 months; 95% confidence interval (CI): 52.1-62.2 months] Conclusion: Within the intrinsic limitations of a retrospective design and small population, our report suggests that volume of disease could be a useful predictive biomarker for patients starting first-line ARSi for mCRPC.
Language	English
Publishing date	2023-03-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359231156147
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Article ; Online: Etelcalcetide Utilization, Dosing Titration, and Chronic Kidney Disease-Mineral and Bone Disease (CKD-MBD) Marker Responses in US Hemodialysis Patients.

Karaboyas, Angelo / Muenz, Daniel / Fuller, Douglas S / Desai, Pooja / Lin, Tzu-Chieh / Robinson, Bruce M / Rossetti, Sandro / Pisoni, Ronald L

American journal of kidney diseases : the official journal of the National Kidney Foundation

2021 Volume 79, Issue 3, Page(s) 362–373

Abstract: Rationale & objective: Clinical trial data have demonstrated the efficacy of etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of etelcalcetide utilization, dosing, effectiveness, ... ...

Abstract	Rationale & objective: Clinical trial data have demonstrated the efficacy of etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of etelcalcetide utilization, dosing, effectiveness, and discontinuation since its US introduction in April 2017. Study design: New-user design within prospective cohort. Setting & participants: 2,596 new users of etelcalcetide from April 2017 through August 2019 in a national sample of adult maintenance HD patients in the US Dialysis Outcomes and Practice Patterns Study (DOPPS). Predictors: Baseline PTH, prior cinacalcet use, initial etelcalcetide dose. Outcome: Trajectories of etelcalcetide dose, chronic kidney disease-mineral and bone disease (CKD-MBD) medications, and levels of PTH, serum calcium, and phosphorus in the 12 months after etelcalcetide initiation. Analytical approach: Cumulative incidence methods for etelcalcetide discontinuation and linear generalized estimating equations for trajectory analyses. Results: By August 2019, etelcalcetide prescriptions increased to 6% of HD patients from their first use in April 2017. Starting etelcalcetide dose was 15 mg/wk in 70% of patients and 7.5 mg/wk in 27% of patients; 49% of new users were prescribed cinacalcet in the prior 3 months. Etelcalcetide discontinuation was 9%, 17%, and 27% by 3, 6, and 12 months after initiation. One year after etelcalcetide initiation, mean PTH levels declined by 40%, from 948 to 566 pg/mL, and the proportion of patients with PTH within target (150-599 pg/mL) increased from 33% to 64% overall, from 0 to 60% among patients with baseline PTH ≥ 600 pg/mL, and from 30% to 63% among patients with prior cinacalcet use. The proportion of patients with serum phosphorus > 5.5 mg/dL decreased from 55% to 45%, while the prevalence of albumin-corrected serum calcium < 7.5 mg/dL remained at 1%-2%. There were increases in use of active vitamin D (from 77% to 87%) and calcium-based phosphate binders (from 41% to 50%) in the 12 months after etelcalcetide initiation. Limitations: Data are unavailable for provider dosing protocols, dose holds, or reasons for discontinuation. Conclusions: In the 12 months after etelcalcetide initiation, patients had large and sustained reductions in PTH levels. These results support the utility of etelcalcetide as an effective therapy to achieve the KDIGO-recommended guidelines for CKD-MBD markers in HD patients.
MeSH term(s)	Adult ; Bone Diseases/complications ; Calcium ; Chronic Kidney Disease-Mineral and Bone Disorder/drug therapy ; Chronic Kidney Disease-Mineral and Bone Disorder/etiology ; Cohort Studies ; Humans ; Hyperparathyroidism, Secondary/etiology ; Minerals ; Parathyroid Hormone ; Peptides ; Prospective Studies ; Renal Dialysis/adverse effects ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/therapy
Chemical Substances	Minerals ; Parathyroid Hormone ; Peptides ; etelcalcetide hydrochloride (72PT5993DU) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-07-15
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2021.05.020
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Article ; Online: Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer.

Passarelli, Anna / Pisano, Carmela / Cecere, Sabrina Chiara / Di Napoli, Marilena / Rossetti, Sabrina / Tambaro, Rosa / Ventriglia, Jole / Gherardi, Federica / Iannacone, Eva / Venanzio, Sergio Setola / Fiore, Francesco / Bartoletti, Michele / Scognamiglio, Giosuè / Califano, Daniela / Pignata, Sandro

Frontiers in immunology

2022 Volume 13, Page(s) 953115

Abstract: Immunotherapy is acquiring a primary role in treating endometrial cancer (EC) with a relevant benefit for many patients. Regardless, patients progressing during immunotherapy or those who are resistant represent an unmet need. The mechanisms of immune ... ...

Abstract	Immunotherapy is acquiring a primary role in treating endometrial cancer (EC) with a relevant benefit for many patients. Regardless, patients progressing during immunotherapy or those who are resistant represent an unmet need. The mechanisms of immune resistance and escape need to be better investigated. Here, we review the major mechanisms of immune escape activated by the indolamine 2,3-dioxygenase 1 (IDO1) pathway in EC and focus on potential therapeutic strategies based on IDO1 signaling pathway control. IDO1 catalyzes the first rate-limiting step of the so-called "kynurenine (Kyn) pathway", which converts the essential amino acid l-tryptophan into the immunosuppressive metabolite l-kynurenine. Functionally, IDO1 has played a pivotal role in cancer immune escape by catalyzing the initial step of the Kyn pathway. The overexpression of IDO1 is also associated with poor prognosis in EC. These findings can lead to advantages in immunotherapy-based approaches as a rationale for overcoming the immune escape. Indeed, besides immune checkpoints, other mechanisms, including the IDO enzymes, contribute to the EC progression due to the immunosuppression induced by the tumor milieu. On the other hand, the IDO1 enzyme has recently emerged as both a promising therapeutic target and an unfavorable prognostic biomarker. This evidence provides the basis for translational strategies of immune combination, whereas IDO1 expression would serve as a potential prognostic biomarker in metastatic EC.
MeSH term(s)	Biomarkers ; Endometrial Neoplasms/therapy ; Female ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Kynurenine/metabolism ; Tryptophan/metabolism
Chemical Substances	Biomarkers ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Kynurenine (343-65-7) ; Tryptophan (8DUH1N11BX)
Language	English
Publishing date	2022-09-02
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.953115
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Article: Stereotactic body radiotherapy with CyberKnife

Borzillo, Valentina / Scipilliti, Esmeralda / Pezzulla, Donato / Serra, Marcello / Ametrano, Gianluca / Quarto, Giuseppe / Perdonà, Sisto / Rossetti, Sabrina / Pignata, Sandro / Crispo, Anna / Di Gennaro, Piergiacomo / D'Alesio, Valentina / Arrichiello, Cecilia / Buonanno, Francesca / Mercogliano, Simona / Russo, Antonio / Tufano, Antonio / Di Franco, Rossella / Muto, Paolo

Frontiers in oncology

2023 Volume 13, Page(s) 1270498

Abstract: Simple summary: Stereotactic body radiotherapy (SBRT) of 35-36.25 Gy in five fractions with the CyberKnife System yields excellent control with low toxicity in low-intermediate-risk prostate cancer patients. We found no differences in biochemical ... ...

Abstract	Simple summary: Stereotactic body radiotherapy (SBRT) of 35-36.25 Gy in five fractions with the CyberKnife System yields excellent control with low toxicity in low-intermediate-risk prostate cancer patients. We found no differences in biochemical control and overall survival in relation to dose. There were no significant differences in toxicity or quality of life between the two groups. Aims: Stereotactic body radiotherapy (SBRT) is an emerging therapeutic approach for low- and intermediate-risk prostate cancer. We present retrospective data on biochemical control, toxicity, and quality of life of CyPro Trial. Materials and methods: A total of 122 patients with low- and intermediate-risk prostate cancer were treated with the CyberKnife System at a dose of 35 Gy or 36.25 Gy in five fractions. Biochemical failure (BF)/biochemical disease-free survival (bDFS) was defined using the Phoenix method (nadir + 2 ng/ml). Acute/late rectal and urinary toxicities were assessed by the Radiation Therapy Oncology Group (RTOG) toxicity scale. Quality of life (QoL) was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and PR25. International Erectile Function Index-5 (IIEF5) and International Prostate Symptom Score (IPSS) questionnaires were administered at baseline, every 3 months after treatment during the first years, and then at 24 months and 36 months. Results: The 1-, 2-, and 5-year DFS rates were 92.9%, 92.9%, and 92.3%, respectively, while the 1-, 2-, and 5-year bDFS rates were 100%, 100%, and 95.7%, respectively. With regard to risk groups or doses, no statistically significant differences were found in terms of DFS or bDFS. Grade 2 urinary toxicity was acute in 10% and delayed in 2% of patients. No Grade 3 acute and late urinary toxicity was observed. Grade 2 rectal toxicity was acute in 8% and late in 1% of patients. No Grade 3-4 acute and late rectal toxicity was observed. Grade 2 acute toxicity appeared higher in the high-dose group (20% in the 36.25-Gy group versus 3% in the 35-Gy group) but was not statistically significant. Conclusion: Our study confirms that SBRT of 35-36.25 Gy in five fractions with the CyberKnife System produces excellent control with low toxicity in patients with low-intermediate-risk prostate cancer. We found no dose-related differences in biochemical control and overall survival. Further confirmation of these results is awaited through the prospective phase of this study, which is still ongoing.
Language	English
Publishing date	2023-11-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1270498
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Article ; Online: Clinical impact of volume of disease and time of metastatic disease presentation on patients receiving enzalutamide or abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer.

Nuzzo, Pier Vitale / Pederzoli, Filippo / Saieva, Calogero / Zanardi, Elisa / Fotia, Giuseppe / Malgeri, Andrea / Rossetti, Sabrina / Valenca Bueno, Loana / Andrade, Livia Maria Q S / Patrikidou, Anna / Mestre, Ricardo Pereira / Modesti, Mikol / Pignata, Sandro / Procopio, Giuseppe / Fornarini, Giuseppe / De Giorgi, Ugo / Russo, Antonio / Francini, Edoardo

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 75

Abstract: Background: Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), ... ...

Abstract	Background: Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy [PLT] or de-novo [DN]) and disease burden (low volume [LV] or high-volume [HV]) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line. Methods: A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first. Results: Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0-66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8-32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002). Conclusion: Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.
MeSH term(s)	Male ; Humans ; Abiraterone Acetate/therapeutic use ; Prednisone/therapeutic use ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/pathology ; Prospective Studies ; Treatment Outcome ; Nitriles ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Chemical Substances	Abiraterone Acetate (EM5OCB9YJ6) ; Prednisone (VB0R961HZT) ; enzalutamide (93T0T9GKNU) ; Nitriles
Language	English
Publishing date	2023-02-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-022-03861-2
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Article ; Online: The genetics of vascular complications in autosomal dominant polycystic kidney disease (ADPKD).

Rossetti, Sandro / Harris, Peter C

Current hypertension reviews

2013 Volume 9, Issue 1, Page(s) 37–43

Abstract: The most important extra-renal manifestation of autosomal dominant polycystic kidney disease (ADPKD) in terms of debilitating injury and premature death is the development of intracranial aneurysms (IAs) and other vascular complications, resulting in ... ...

Abstract	The most important extra-renal manifestation of autosomal dominant polycystic kidney disease (ADPKD) in terms of debilitating injury and premature death is the development of intracranial aneurysms (IAs) and other vascular complications, resulting in subarachnoid hemorrhage (SAH). IAs are found at a rate approximately five times higher in ADPKD patients than in the general population and in patients with a family history of SAH/IAs the frequency is elevated further three to five times, indicating the importance of genetic factors in its etiology. Expression of the ADPKD gene products, polycystin-1 (PKD1) and polycystin-2 (PKD2), in vascular smooth muscle and the endothelium, and evidence that reduced levels of these proteins leads to IA development in mouse models, suggests a direct role of these proteins in the vascular disease. PKD1 and PKD2 patients seem equally likely to develop IAs, while patients with mutations to the 5' half of PKD1 may more likely have vascular complications. Genome wide association and candidate studies of multiplex families with IAs without ADPKD have identified a number of genes/proteins that may be risk factors for the development of IAs. These candidate proteins largely have roles in the maintenance and remodeling of the arterial wall of small brain arteries. The development of the genetic methodologies of massively parallel sequencing mean it is now possible to test these and other candidates in ADPKD families with multiplex and singleton IA cases. Identifying strong modifiers of this phenotype will be important for prioritizing patients for presymptomatic screening and interventions.
MeSH term(s)	Animals ; Endothelium, Vascular/metabolism ; Genetic Association Studies ; Humans ; Intracranial Aneurysm/genetics ; Intracranial Aneurysm/metabolism ; Muscle, Smooth, Vascular/metabolism ; Mutation ; Polycystic Kidney, Autosomal Dominant/genetics ; TRPP Cation Channels/genetics
Chemical Substances	TRPP Cation Channels ; polycystic kidney disease 1 protein ; polycystic kidney disease 2 protein
Language	English
Publishing date	2013-08-26
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	1875-6506
ISSN (online)	1875-6506
DOI	10.2174/1573402111309010007
Database	MEDical Literature Analysis and Retrieval System OnLINE

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