2.Association Between Diabetes and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis of Observational Studies
Ana Paula PAGANO ; Bruna Ramos da SILVA ; Flávio Teixeira VIEIRA ; Luiz Fernando Meira FILHO ; Sarah A. PURCELL ; John D. LEWIS ; Michelle L. MACKENZIE ; Paula J. ROBSON ; Jennifer E. VENA ; Flávia Moraes SILVA ; Carla M. PRADO
The World Journal of Men's Health 2025;43(2):304-320
Purpose:
Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk.
Materials and Methods:
A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.
Results:
Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low.
Conclusions
Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.
3.Lipid Priming of Adipose Mesenchymal Stromal Cells with Docosahexaenoic Acid: Impact on Cell Differentiation, Senescence and the Secretome Neuroregulatory Profile
Jonas CAMPOS ; Belém SAMPAIO-MARQUES ; Diogo SANTOS ; Sandra BARATA-ANTUNES ; Miguel RIBEIRO ; Sofia C. SERRA ; Tiffany S. PINHO ; João CANTO-GOMES ; Ana MAROTE ; Margarida CORTEZ ; Nuno A. SILVA ; Adina T. MICHAEL-TITUS ; António J. SALGADO
Tissue Engineering and Regenerative Medicine 2025;22(1):113-128
BACKGROUND:
Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential.
METHODS:
Comprehensive dose–response and time-course assays were carried to determine an optimal priming protocol. Secretome total protein measurements were taken in association with cell viability, density and morphometric assessments. Cell identity and differentiation capacity were studied by flow cytometry and lineage-specific markers. Cell growth was assessed by trypan-blue exclusion and senescence was probed over time using SA-b-gal, morphometry and gene expression. Secretomes were tested for their ability to support differentiation and neurite outgrowth of human neural progenitor cells (hNPCs). Neuroregulatory proteins in the secretome were identified using multiplex membrane arrays.
RESULTS:
Priming with 40 lM DHA for 72 h significantly enhanced the biosynthetic capacity of ASCs, producing a secretome with higher protein levels and increased metabolic viability. DHA priming enhanced ASCs adipogenic differentiation and adapted their responses to replicative senescence induction. Furthermore, priming increased concentrations of neurotrophic factors in the secretome promoting neurite outgrowth and modulating the differentiation of hNPCs.
CONCLUSIONS
These results provide proof-of-concept evidence that DHA priming is a viable strategy to improve the neuroregulatory profile of ASCs.
4.Anesthesia management for total robotic liver transplantation: Inaugural case series in Europe
Ana DUARTE ; Vasyl KATERENCHUK ; Rita POEIRA ; Paula ROCHA ; Filipe PISSARRA ; Margarida CANAS ; Sandra DIAS ; Diogo ANDRADE ; Hugo Pinto MARQUES ; Susana CADILHA ; José Silva PINTO
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(1):88-94
Robotic liver transplantation represents a cutting-edge technique that may surpass traditional open surgery. Nonetheless, it introduces unique anesthetic challenges, including extended pneumoperitoneum, restricted patient access, and a risk of undetected blood loss. This article describes an anesthetic approach and patient outcomes for the first four total robotic liver transplants performed at a tertiary university hospital in Portugal, along with inaugural procedures of their kind in Europe. We retrospectively analyzed surgical and anesthetic data from four patients who underwent total robotic liver transplantation from February to April 2024. Data encompassed clinical profile, preoperative assessment, surgical and anesthesia details, postoperative course, and outcomes. Patients’ age ranged from 51 to 69 years. Their cirrhosis was primarily due to alcohol use, hepatitis C virus infection, hepatocellular carcinoma, or nonalcoholic steatohepatitis. General anesthesia was administered. Hemodynamic monitoring and goal-directed fluid therapy were conducted using a PiCCO system. Blood loss varied from 1,000 to 5,000 mL. Blood products were transfused as needed. All donor livers underwent hypothermic oxygenated machine perfusion before transplantation. After surgery, two patients were immediately extubated, while two required extended ventilation. Hospital stays ranged from 10 to 40 days. The 30-day survival rate was 100%. This initial case series affirmed the feasibility and safety of total robotic liver transplantation for carefully selected patients, yielding favorable short-term results. Anesthetic management can rely on proactive strategies, acute situational awareness, and effective multidisciplinary collaboration.
5.Association Between Diabetes and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis of Observational Studies
Ana Paula PAGANO ; Bruna Ramos da SILVA ; Flávio Teixeira VIEIRA ; Luiz Fernando Meira FILHO ; Sarah A. PURCELL ; John D. LEWIS ; Michelle L. MACKENZIE ; Paula J. ROBSON ; Jennifer E. VENA ; Flávia Moraes SILVA ; Carla M. PRADO
The World Journal of Men's Health 2025;43(2):304-320
Purpose:
Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk.
Materials and Methods:
A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.
Results:
Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low.
Conclusions
Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.
6.Lipid Priming of Adipose Mesenchymal Stromal Cells with Docosahexaenoic Acid: Impact on Cell Differentiation, Senescence and the Secretome Neuroregulatory Profile
Jonas CAMPOS ; Belém SAMPAIO-MARQUES ; Diogo SANTOS ; Sandra BARATA-ANTUNES ; Miguel RIBEIRO ; Sofia C. SERRA ; Tiffany S. PINHO ; João CANTO-GOMES ; Ana MAROTE ; Margarida CORTEZ ; Nuno A. SILVA ; Adina T. MICHAEL-TITUS ; António J. SALGADO
Tissue Engineering and Regenerative Medicine 2025;22(1):113-128
BACKGROUND:
Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential.
METHODS:
Comprehensive dose–response and time-course assays were carried to determine an optimal priming protocol. Secretome total protein measurements were taken in association with cell viability, density and morphometric assessments. Cell identity and differentiation capacity were studied by flow cytometry and lineage-specific markers. Cell growth was assessed by trypan-blue exclusion and senescence was probed over time using SA-b-gal, morphometry and gene expression. Secretomes were tested for their ability to support differentiation and neurite outgrowth of human neural progenitor cells (hNPCs). Neuroregulatory proteins in the secretome were identified using multiplex membrane arrays.
RESULTS:
Priming with 40 lM DHA for 72 h significantly enhanced the biosynthetic capacity of ASCs, producing a secretome with higher protein levels and increased metabolic viability. DHA priming enhanced ASCs adipogenic differentiation and adapted their responses to replicative senescence induction. Furthermore, priming increased concentrations of neurotrophic factors in the secretome promoting neurite outgrowth and modulating the differentiation of hNPCs.
CONCLUSIONS
These results provide proof-of-concept evidence that DHA priming is a viable strategy to improve the neuroregulatory profile of ASCs.
7.Association Between Diabetes and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis of Observational Studies
Ana Paula PAGANO ; Bruna Ramos da SILVA ; Flávio Teixeira VIEIRA ; Luiz Fernando Meira FILHO ; Sarah A. PURCELL ; John D. LEWIS ; Michelle L. MACKENZIE ; Paula J. ROBSON ; Jennifer E. VENA ; Flávia Moraes SILVA ; Carla M. PRADO
The World Journal of Men's Health 2025;43(2):304-320
Purpose:
Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk.
Materials and Methods:
A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.
Results:
Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low.
Conclusions
Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.
8.Lipid Priming of Adipose Mesenchymal Stromal Cells with Docosahexaenoic Acid: Impact on Cell Differentiation, Senescence and the Secretome Neuroregulatory Profile
Jonas CAMPOS ; Belém SAMPAIO-MARQUES ; Diogo SANTOS ; Sandra BARATA-ANTUNES ; Miguel RIBEIRO ; Sofia C. SERRA ; Tiffany S. PINHO ; João CANTO-GOMES ; Ana MAROTE ; Margarida CORTEZ ; Nuno A. SILVA ; Adina T. MICHAEL-TITUS ; António J. SALGADO
Tissue Engineering and Regenerative Medicine 2025;22(1):113-128
BACKGROUND:
Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential.
METHODS:
Comprehensive dose–response and time-course assays were carried to determine an optimal priming protocol. Secretome total protein measurements were taken in association with cell viability, density and morphometric assessments. Cell identity and differentiation capacity were studied by flow cytometry and lineage-specific markers. Cell growth was assessed by trypan-blue exclusion and senescence was probed over time using SA-b-gal, morphometry and gene expression. Secretomes were tested for their ability to support differentiation and neurite outgrowth of human neural progenitor cells (hNPCs). Neuroregulatory proteins in the secretome were identified using multiplex membrane arrays.
RESULTS:
Priming with 40 lM DHA for 72 h significantly enhanced the biosynthetic capacity of ASCs, producing a secretome with higher protein levels and increased metabolic viability. DHA priming enhanced ASCs adipogenic differentiation and adapted their responses to replicative senescence induction. Furthermore, priming increased concentrations of neurotrophic factors in the secretome promoting neurite outgrowth and modulating the differentiation of hNPCs.
CONCLUSIONS
These results provide proof-of-concept evidence that DHA priming is a viable strategy to improve the neuroregulatory profile of ASCs.
9.Anesthesia management for total robotic liver transplantation: Inaugural case series in Europe
Ana DUARTE ; Vasyl KATERENCHUK ; Rita POEIRA ; Paula ROCHA ; Filipe PISSARRA ; Margarida CANAS ; Sandra DIAS ; Diogo ANDRADE ; Hugo Pinto MARQUES ; Susana CADILHA ; José Silva PINTO
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(1):88-94
Robotic liver transplantation represents a cutting-edge technique that may surpass traditional open surgery. Nonetheless, it introduces unique anesthetic challenges, including extended pneumoperitoneum, restricted patient access, and a risk of undetected blood loss. This article describes an anesthetic approach and patient outcomes for the first four total robotic liver transplants performed at a tertiary university hospital in Portugal, along with inaugural procedures of their kind in Europe. We retrospectively analyzed surgical and anesthetic data from four patients who underwent total robotic liver transplantation from February to April 2024. Data encompassed clinical profile, preoperative assessment, surgical and anesthesia details, postoperative course, and outcomes. Patients’ age ranged from 51 to 69 years. Their cirrhosis was primarily due to alcohol use, hepatitis C virus infection, hepatocellular carcinoma, or nonalcoholic steatohepatitis. General anesthesia was administered. Hemodynamic monitoring and goal-directed fluid therapy were conducted using a PiCCO system. Blood loss varied from 1,000 to 5,000 mL. Blood products were transfused as needed. All donor livers underwent hypothermic oxygenated machine perfusion before transplantation. After surgery, two patients were immediately extubated, while two required extended ventilation. Hospital stays ranged from 10 to 40 days. The 30-day survival rate was 100%. This initial case series affirmed the feasibility and safety of total robotic liver transplantation for carefully selected patients, yielding favorable short-term results. Anesthetic management can rely on proactive strategies, acute situational awareness, and effective multidisciplinary collaboration.

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