Publications by authors named "Joana Neves"

100 Publications

Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance.

Nat Commun 2021 06 17;12(1):3636. Epub 2021 Jun 17.

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA.

To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function of DNA polymerase Polθ, including ART558. ART558 inhibits the major Polθ-mediated DNA repair process, Theta-Mediated End Joining, without targeting Non-Homologous End Joining. In addition, ART558 elicits DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumour cells and enhances the effects of a PARP inhibitor. Genetic perturbation screening revealed that defects in the 53BP1/Shieldin complex, which cause PARP inhibitor resistance, result in in vitro and in vivo sensitivity to small molecule Polθ polymerase inhibitors. Mechanistically, ART558 increases biomarkers of single-stranded DNA and synthetic lethality in 53BP1-defective cells whilst the inhibition of DNA nucleases that promote end-resection reversed these effects, implicating these in the synthetic lethal mechanism-of-action. Taken together, these observations describe a drug class that elicits BRCA-gene synthetic lethality and PARP inhibitor synergy, as well as targeting a biomarker-defined mechanism of PARPi-resistance.
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http://dx.doi.org/10.1038/s41467-021-23463-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211653PMC
June 2021

Growth and renal function dynamics of renal oncocytomas on active surveillance.

BJU Int 2021 May 28. Epub 2021 May 28.

Division of Surgery and Interventional Science, University College London.

Objectives: To study the natural history of renal oncocytomas and address indications for intervention by determining how growth associates with renal function over time, the reasons for surgery and ablation, and disease-specific survival.

Patients And Methods: Retrospective cohort of consecutive patients with renal oncocytoma on active surveillance reviewed at the Specialist Centre for Kidney Cancer at Royal Free London NHS Foundation Trust (2012 to 2019). Comparison between groups was tested using the Mann-Whitney U and the Chi-square tests. A mixed-effects model with a random intercept for patient was used to study the longitudinal association between tumour size and estimated glomerular filtration rate (eGFR).

Results: Longitudinal data from 98 patients with 101 lesions was analysed. Most patients were male (68.3%), median age was 69 years (IQR 13). The median follow-up was 29 months (IQR 26). Most lesions were small renal masses, 24% measured over 4 cm. Over half (64.4%) grew at a median rate of 2 mm per year (IQR 4). No association was observed between tumour size and eGFR over time (p=0.871). Nine lesions (8.9%) were subsequently treated. Two deaths were reported, neither were related to the diagnosis of renal oncocytoma.

Conclusion: Natural history data from the largest active surveillance cohort of renal oncocytomas to date show that renal function does not seem to be negatively impacted by growing oncocytomas, and confirms clinical outcomes are excellent after a median follow up of over 2 years. Active surveillance should be considered the gold standard management of renal oncocytomas up to 7cm.
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http://dx.doi.org/10.1111/bju.15499DOI Listing
May 2021

Renal oncocytoma: landscape of diagnosis and management.

BJU Int 2021 May 26. Epub 2021 May 26.

Division of Surgery and Interventional Science, University College London, London, UK.

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http://dx.doi.org/10.1111/bju.15496DOI Listing
May 2021

The European Association of Urology COVID Intermediate-priority Group is Poorly Predictive of Pathological High Risk Among Patients with Renal Tumours.

Eur Urol 2021 Aug 20;80(2):265-267. Epub 2021 May 20.

UCL Medical School, University College London, London, UK; Specialist Centre For Kidney Cancer, Royal Free London NHS Foundation Trust, London, UK. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2021.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136273PMC
August 2021

MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function.

J Immunol 2021 Jun 21;206(11):2725-2739. Epub 2021 May 21.

School of Immunology and Microbial Sciences, King's College London, London, United Kingdom;

Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor-biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, and expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions.
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http://dx.doi.org/10.4049/jimmunol.2000647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610861PMC
June 2021

Impact of the first surge of the COVID-19 pandemic on a tertiary referral centre for kidney cancer.

BJU Int 2021 May 8. Epub 2021 May 8.

Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, London, UK.

Objective: To analyse the impact of the COVID-19 pandemic on a centralized specialist kidney cancer care pathway.

Materials And Methods: We conducted a retrospective analysis of patient and pathway characteristics including prioritization strategies at the Specialist Centre for Kidney Cancer located at the Royal Free London NHS Foundation Trust (RFH) before and during the surge of COVID-19.

Results: On 18 March 2020 all elective surgery was halted at RFH to redeploy resources and staff for the COVID-19 surge. Prioritizing of patients according to European Association of Urology guidance was introduced. Clinics and the specialist multidisciplinary team (SMDT) meetings were maintained with physical distancing, kidney surgery was moved to a COVID-protected site, and infection prevention measurements were enforced. During the 7 weeks of lockdown (23 March to 10 May 2020), 234 cases were discussed at the SMDT meetings, 53% compared to the 446 cases discussed in the 7 weeks pre-lockdown. The reduction in referrals was more pronounced for small and asymptomatic renal masses. Of 62 low-priority cancer patients, 27 (43.5%) were deferred. Only one (4%) COVID-19 infection occurred postoperatively, and the patient made a full recovery. No increase in clinical or pathological upstaging could be detected in patients who underwent deferred surgery compared to pre-COVID practice.

Conclusion: The first surge of the COVID-19 pandemic severely impacted diagnosis, referral and treatment of kidney cancer at a tertiary referral centre. With a policy of prioritization and COVID-protected pathways, capacity for time-sensitive oncological interventions was maintained and no immediate clinical harm was observed.
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http://dx.doi.org/10.1111/bju.15441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239749PMC
May 2021

The Relationship between Mucins and Ulcerative Colitis: A Systematic Review.

J Clin Med 2021 Apr 30;10(9). Epub 2021 Apr 30.

Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Science, King's College London, London SE1 9RT, UK.

Mucins are a family of glycosylated proteins which are the primary constituents of mucus and play a dynamic role in the regulation of the protective mucosal barriers throughout the human body. Ulcerative colitis (UC) is an Inflammatory Bowel Disease (IBD) characterised by continuous inflammation of the inner layer of the large intestine, and in this systematic review we analyse currently available data to determine whether alterations exist in mucin activity in the colonic mucosa of UC patients. Database searches were conducted to identify studies published between 1990 and 2020 that assess the role of mucins in cohorts of UC patients, where biopsy specimens were resected for analysis and control groups were included for comparison. 5497 articles were initially identified and of these 14 studies were systematically selected for analysis, a further 2 articles were identified through citation chaining. Therefore, 16 studies were critically reviewed. 13 of these studies assessed the role of MUC2 in UC and the majority of articles indicated that alterations in MUC2 structure or synthesis had an impact on the colonic mucosa, although conflicting results were presented regarding MUC2 expression. This review highlights the importance of further research to enhance our understanding of mucin regulation in UC and summarises data that may inform future studies.
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http://dx.doi.org/10.3390/jcm10091935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125602PMC
April 2021

Pattern, timing and predictors of recurrence after surgical resection of chromophobe renal cell carcinoma.

World J Urol 2021 Apr 13. Epub 2021 Apr 13.

Division of Surgery and Interventional Science, University College London, London, UK.

Purpose: Currently there are no specific guidelines for the post-operative follow-up of chromophobe renal cell carcinoma (chRCC). We aimed to evaluate the pattern, location and timing of recurrence after surgery for non-metastatic chRCC and establish predictors of recurrence and cancer-specific death.

Methods: Retrospective analysis of consecutive surgically treated non-metastatic chRCC cases from the Royal Free London NHS Foundation Trust (UK, 2015-2019) and the international collaborative database RECUR (15 institutes, 2006-2011). Kaplan-Meier curves were plotted. The association between variables of interest and outcomes were analysed using univariate and multivariate Cox proportional hazards regression models with shared frailty for data source.

Results: 295 patients were identified. Median follow-up was 58 months. The five and ten-year recurrence-free survival rates were 94.3% and 89.2%. Seventeen patients (5.7%) developed recurrent disease, 13 (76.5%) with distant metastases. 54% of metastatic disease diagnoses involved a single organ, most commonly the bone. Early recurrence (< 24 months) was observed in 8 cases, all staged ≥ pT2b. 30 deaths occurred, of which 11 were attributed to chRCC. Sarcomatoid differentiation was rare (n = 4) but associated with recurrence and cancer-specific death on univariate analysis. On multivariate analysis, UICC/AJCC T-stage ≥ pT2b, presence of coagulative necrosis, and positive surgical margins were predictors of recurrence and cancer-specific death.

Conclusion: Recurrence and death after surgically resected chRCC are rare. For completely excised lesions ≤ pT2a without coagulative necrosis or sarcomatoid features, prognosis is excellent. These patients should be reassured and follow-up intensity curtailed.
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http://dx.doi.org/10.1007/s00345-021-03683-9DOI Listing
April 2021

T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells.

Front Immunol 2020 2;11:623324. Epub 2021 Feb 2.

School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.

Innate lymphoid cells (ILC) play a significant immunological role at mucosal surfaces such as the intestine. T-bet-expressing group 1 innate lymphoid cells (ILC1) are believed to play a substantial role in inflammatory bowel disease (IBD). However, a role of T-bet-negative ILC3 in driving colitis has also been suggested in mouse models questioning T-bet as a critical factor for IBD. We report here that T-bet deficient mice had a greater cellularity of NKp46-negative ILC3 correlating with enhanced expression of RORγt and IL-7R, but independent of signaling through STAT1 or STAT4. We observed enhanced neutrophilia in the colonic lamina propria (cLP) of these animals, however, we did not detect a greater risk of T-bet-deficient mice to develop spontaneous colitis. Furthermore, by utilizing an fate-mapping approach, we identified a population of T-bet-positive precursors in NKp46-negative ILC3s. These data suggest that T-bet controls ILC3 cellularity, but does do not drive a pathogenic role of ILC3 in mice with a conventional specific pathogen-free microbiota.
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http://dx.doi.org/10.3389/fimmu.2020.623324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884460PMC
June 2021

Biocompatibility of self-adhesive resin cement with fibroblast cells.

J Prosthet Dent 2021 Apr 15;125(4):705.e1-705.e7. Epub 2021 Feb 15.

Professor, Centro de Investigação interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz, Caparica, Portugal. Electronic address:

Statement Of Problem: Dental cements that release monomers that negatively impact adjacent oral soft tissues may adversely affect clinical outcomes. However, in vitro studies evaluating the cytotoxic and genotoxic potential of substances released from dental cements are lacking.

Purpose: The purpose of this in vitro study was to define and compare the cytotoxicity and genotoxicity of the eluates of a self-adhesive resin cement (RelyX Unicem 2 Automix) autopolymerized and light polymerized with 2 other types of luting cements: a glass ionomer cement (Ketac Cem Easymix) and a resin-modified glass ionomer cement (Ketac Cem Plus).

Material And Methods: The eluates were prepared, and 3T3 mouse fibroblast cells were exposed for 24 hours to serial eluate dilutions of the 3 types of cement. Cytotoxicity was determined by using a cell viability assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays. Genotoxic effects were determined by using the cytokinesis-block micronucleus assay.

Results: Cell viability was higher in the presence of the glass ionomer cement eluate than of the resin-modified glass ionomer cement and resin cement eluates. A pronounced decrease in viability was found when the cells were exposed to undiluted samples of resin-modified glass ionomer cement (around 50%) or resin cement (around 80% to 90%). No significant difference in cell viability was found between autopolymerized and light-polymerized resin cements. All cements induced a dose-dependent response of mononucleated cell formation. However, only the resin cements showed double strand breaks significant differences in the deoxyribonucleic acid (DNA) molecules against the basal DNA lesions that occurred spontaneously.

Conclusions: The glass ionomer cement was not found to be cytotoxic or genotoxic, whereas the eluates derived from the resin-modified glass ionomer cement and resin cement, independently of the polymerization method, were cytotoxic in fibroblast cells. Maximum cytotoxicity was observed in the presence of resin cement, which also showed genotoxicity, independently of being light polymerized.
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http://dx.doi.org/10.1016/j.prosdent.2021.01.002DOI Listing
April 2021

Mild Attenuation of the Pulmonary Inflammatory Response in a Mouse Model of Hereditary Hemochromatosis Type 4.

Front Physiol 2020 13;11:589351. Epub 2021 Jan 13.

Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany.

The respiratory tract is constantly exposed to pathogens that require iron for proliferation and virulence. Pulmonary iron levels are increased in several lung diseases and associated with increased susceptibility to infections. However, regulation of lung iron homeostasis and its cross talk to pulmonary immune responses are largely unexplored. Here we investigated how increased lung iron levels affect the early pulmonary inflammatory response. We induced acute local pulmonary inflammation via aerosolized LPS in a mouse model of hereditary hemochromatosis type 4 ( ), which is hallmarked by systemic and pulmonary iron accumulation, specifically in alveolar macrophages. We show that mice display a mild attenuation in the LPS-induced pulmonary inflammatory response, with a reduced upregulation of some pro-inflammatory cytokines and chemokines. Despite mildly reduced cytokine levels, there is no short-term impairment in the recruitment of neutrophils into the bronchoalveolar space. These data suggest that increased pulmonary iron levels do not strongly alter the acute inflammatory response of the lung.
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http://dx.doi.org/10.3389/fphys.2020.589351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838636PMC
January 2021

Radiomics to better characterize small renal masses.

World J Urol 2021 Jan 26. Epub 2021 Jan 26.

Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, London, UK.

Purpose: Radiomics is a specific field of medical research that uses programmable recognition tools to extract objective information from standard images to combine with clinical data, with the aim of improving diagnostic, prognostic, and predictive accuracy beyond standard visual interpretation. We performed a narrative review of radiomic applications that may support improved characterization of small renal masses (SRM). The main focus of the review was to identify and discuss methods which may accurately differentiate benign from malignant renal masses, specifically between renal cell carcinoma (RCC) subtypes and from angiomyolipoma without visible fat (fat-poor AML) and oncocytoma. Furthermore, prediction of grade, sarcomatoid features, and gene mutations would be of importance in terms of potential clinical utility in prognostic stratification and selecting personalised patient management strategies.

Methods: A detailed search of original articles was performed using the PubMed-MEDLINE database until 20 September 2020 to identify the English literature relevant to radiomics applications in renal tumour assessment. In total, 42 articles were included in the analysis in 3 main categories related to SRM: prediction of benign versus malignant SRM, subtypes, and nuclear grade, and other features of aggressiveness.

Conclusion: Overall, studies reported the superiority of radiomics over expert radiological assessment, but were mainly of retrospective design and therefore of low-quality evidence. However, it is clear that radiomics is an attractive modality that has the potential to improve the non-invasive diagnostic accuracy of SRM imaging and prediction of its natural behaviour. Further prospective validation studies of radiomics are needed to augment management algorithms of SRM.
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http://dx.doi.org/10.1007/s00345-021-03602-yDOI Listing
January 2021

Chikungunya arthritis - should we expect it to become more common in Portuguese rheumatology?

Acta Reumatol Port 2020 Oct-Dec;45(4):298-300

Hospital de Braga.

Chikungunya virus is known to cause acute disease characterized by fever, rash, myalgias, conjunctivitis and arthritis, having potential to cause chronic musculoskeletal disease, namely persistent arthritis. The area of spread of the virus in the world has been increasing and the migratory flows make the occurrence of Chikungunya induced chronic arthritis more and more scattered. Data regarding the experience of Portuguese rheumatology centres in identifying and treating chronic ChikV induced arthritis are not available. The authors describe the diagnosis and treatment aspects of three cases of "imported" Chikungunya induced chronic arthritis, briefly discuss its approach in the light of current knowledge and alert to the possibility this situation may become more prevalent in the Portuguese rheumatology setting.
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January 2021

Are we overlooking osteoarthritis? - A comparative study of pain, function and quality of life in patiens with hand osteoarthritis and rheumatoid arthritis.

Acta Reumatol Port 2020 Jul-Sep;45(3):233-234

Hospital de Braga.

Osteoarthritis (OA) is frequently regarded by patients and health care providers as a normal consequence of ageing and a minor condition. In contrast, rheumatoid arthritis (RA) is a pathological condition that usually requires prolonged treatment and regular Rheumatology follow-up. Pain and physical limitations are hallmarks of both conditions and some previous studies suggest that OA and RA may have a similar burden for both groups of patients although those works usually do not take into account the inflammatory activity of RA. With this work, the authors compare levels of pain, physical disability and health-related quality of life in patients with primary hand osteoarthritis (hOA) and with RA - active disease (aRA) or in remission (rRA). The results show that hOA may have similar or even higher burden of pain than RA even with clinically relevant inflammatory activity in hand joints. Rather than suggesting that OA could be as severe as RA (or more or less severe), this brief study highlights OA as a cause of severe pain, which should lead us to try to achieve better symptom control for these patients and encourage rheumatologists to endeavor efforts to perform more studies in the field of OA.
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November 2020

Biochar in soil mitigates dimethoate hazard to soil pore water exposed biota.

J Hazard Mater 2020 12 25;400:123304. Epub 2020 Jun 25.

CESAM - Centre for Environmental and Marine Studies, Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address:

Soil contamination is a worldwide problem urging for mitigation. Biochar is a carbonaceous material used as soil amendment that can immobilize chemical compounds, potentially turning them unavailable for soil biota. The aim of our study was to evaluate biochar's capacity to immobilize dimethoate in soil and, therefore, decreasing the toxicity to soil organisms. Two biochar application rates (2.5% and 5% w/w) were chosen to assess dimethoate potential immobilization, looking at changes in its toxicity to the collembolan Folsomia candida and the plant Brassica rapa upon soil amendment. Complementarily, chemical analyses were performed on soil pore water. Results showed that biochar may sorb and decrease dimethoate concentrations in soil pore water, influencing dimethoate bioavailability and consequent toxicity. Contrary to dimethoate solo impact on collembolans (LC 0.69 mg kg, EC 0.46 mg kg), their survival rate and offspring production were not affected by dimethoate when biochar was applied, regardless of application rate (LC and EC > 1.6 mg kg). Shoot length, fresh and dry weights of B. rapa were less affected by dimethoate upon biochar addition (EC values increase for all endpoints). Our study shows that biochar may contribute to decrease dimethoate bioavailability and toxicity to soil porewater exposed organisms.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123304DOI Listing
December 2020

ILC1 drive intestinal epithelial and matrix remodelling.

Nat Mater 2021 02 7;20(2):250-259. Epub 2020 Sep 7.

Centre for Craniofacial and Regenerative Biology, King's College London, London, UK.

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6 epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.
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http://dx.doi.org/10.1038/s41563-020-0783-8DOI Listing
February 2021

Cutaneous vasculitis and granulomatous hepatitis as paradoxical adverse events of Infliximab.

Acta Reumatol Port 2020 Apr-Jun;45(2):156-157

Hospital de Braga.

Biological agents revolutionised the treatment of inflammatory arthropathies. Paradoxical adverse events (PAEs) are rare immunological side effects caused by such agents. The authors report concurrent presentation of two rare PAEs of tumor-necrosis-factor alpha inhibitors (iTNFa) - cutaneous vasculitis and granulomatous hepatitis - in a patient with psoriatic arthritis treated with infliximab and briefly discuss aspects of diagnosis, pathophysiology and management of such events in light of the available evidence.
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July 2021

Physician-patient agreement at a rheumatology consultation - construction and validation of a consultation assessment instrument.

Acta Reumatol Port 2020 Apr-Jun;45(2):89-94

Unidade Local de Saúde do Alto Minho.

Objectives: After consultations, the physician's perceptions differ from the patient's perceptions concerning illness level, cause, and nature of the problem and content of the consultation. Agreement on problems requiring follow-up was associated with a better outcome. The primary aim of this study was to build and validate an instrument that could assess physician-patient agreement in the rheumatology consultation. The secondary objective was to assess agreement association with patient's clinical and sociodemographic data.

Materials And Methods: A ten-item questionnaire - "Consultation Assessment Instrument" (CAI) - was developed for this study to assess the physician-patient agreement. Ten physicians and 102 patients diagnosed with an inflammatory joint disease under biological therapy were included. The items were evaluated and the index of proportional agreement for the dichotomized answers "agree" (Ppos) and "disagree" (Pneg) was calculated.

Results: Consultation satisfaction was the item with the highest agreement. On the opposite end, the item about the explanation of treatment importance was the item with the lowest agreement between patient and physician. Except for one item, the high level of agreement between patient and physician was due to a higher Ppos. Index of proportional agreement was high for 9 of the 10 items (0.816≤ Iv ≤0.990). Patients with lower disease activity scores had a more positive experience. A good internal consistency was obtained for both patient's and physician's questionnaire (α = 0.88 and α = 0.80, respectively).

Conclusions: Both patient and physician showed a positive experience towards Rheumatology consultation. Physician-patient agreement was high in the majority of the consultation aspects (mean Iv = 0,93). A good internal consistency was obtained for both patient's and physician's questionnaire. CAI could be useful as a mental checklist in daily practice or as an educational tool for training consultation skills.
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July 2021

The Role of Tocilizumab in the Treatment of Adult-Onset Still Disease-Report of a Tertiary Single-Center Experience.

J Clin Rheumatol 2020 Jul 6. Epub 2020 Jul 6.

Serviço de Reumatologia do Hospital de Braga, Hospital de Braga, Braga, Portugal Hospital de Braga, Braga, Portugal.

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http://dx.doi.org/10.1097/RHU.0000000000001478DOI Listing
July 2020

Oncocytoma: risk of promoting unnecessary surgery.

World J Urol 2020 Jul 9. Epub 2020 Jul 9.

Division of Surgery and Interventional Science, University College London, London, UK.

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http://dx.doi.org/10.1007/s00345-020-03347-0DOI Listing
July 2020

Salivary gland ultrasound findings are associated with clinical and serologic features in primary Sjögren's syndrome patients.

Acta Reumatol Port 2020 Jan-Mar;45(1):76-77

Unidade Local de Saúde do Alto Minho.

Objective: Salivary gland ultrasound (SGUS) has been applied in the diagnosis of primary Sjögren's syndrome (pSS). To investigate the association of SGUS findings with clinical and analytical features of pSS patients.

Material And Methods: 54 pSS patients underwent SGUS evaluation. The parenchymal homogeneity of bilateral parotid and submandibular glands was graded using a score of 0 (normal) to 4 (gross inhomogeneity). Patients were classified into two groups according to the highest SGUS score obtained. The grades 1 and 2 were considered to be normal and grades 3 and 4 to represent pathological SGUS findings. Demographic, clinical and laboratorial data were collected and compared between the groups.

Results: Nineteen of 54 patients had pathological SGUS findings. These were associated with higher ESSDAI and positivity for rheumatoid factor and anti-SSB antibody. Anti-SSB antibody was strongly and independently associated with pathological US findings in the salivary gland of pSS patients.

Conclusion: This study provides further evidence that salivary gland ultrasound is linked to clinical and autoimmunity profile in pSS and confirm what has been reported in the literature. SGUS represents a useful imaging tool for diagnostic and prognostic of pSS.
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June 2021

The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic three-dimensional renal tumouroids.

J Tissue Eng 2020 Jan-Dec;11:2041731420920597. Epub 2020 May 18.

Research Department of Surgical Biotechnology, Division of Surgery & Interventional Science, University College London, London, UK.

Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia, while the more 'resistant' CAKI-2 tumouroids showed no decrease in viability, 786-O tumouroids required higher Pazopanib concentrations to induce cell death. In complex tumouroids, Pazopanib exposure led to a reduction in the overall cell viability (p < 0.0001), disruption of endothelial networks and direct killing of renal cell carcinoma cells. We report a biomimetic multicellular tumouroid for drug testing, suitable for agents whose primary target is not confined to cancer cells.
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http://dx.doi.org/10.1177/2041731420920597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238304PMC
May 2020

An overview of study designs.

Br J Hosp Med (Lond) 2020 May 4;81(5):1-6. Epub 2020 May 4.

Division of Surgery and Interventional Sciences, University College London, London, UK.

The numbers of clinical trials have increased exponentially over the last decade, amplifying the pressure to select an appropriate study design to obtain reliable and valid evidence. The ability to find, critically appraise and use evidence to develop new interventions is fundamental to evidence-based medicine. Different study designs have their own advantages and disadvantages, and provide different evidentiary value. This article provides an overview of clinical trials, illustrating that, ultimately, the study design chosen needs to meet experimental and funding limitations, while minimising error.
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http://dx.doi.org/10.12968/hmed.2020.0127DOI Listing
May 2020

Severe and Uncommon Features of Gouty Arthropathy.

J Clin Rheumatol 2020 Apr 23. Epub 2020 Apr 23.

From the Serviço de Reumatologia, Hospital de Braga, Braga, Portugal.

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http://dx.doi.org/10.1097/RHU.0000000000001385DOI Listing
April 2020

Muscle stem cell aging: identifying ways to induce tissue rejuvenation.

Mech Ageing Dev 2020 06 18;188:111246. Epub 2020 Apr 18.

Department of Experimental & Health Sciences, University Pompeu Fabra (UPF), CIBERNED, ICREA, 08003, Barcelona, Spain; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28019, Madrid, Spain. Electronic address:

Aging is characterized by the functional and regenerative decline of tissues and organs. This regenerative decline is a consequence of the numerical and functional loss of adult stem cells, which are the corner stone of tissue homeostasis and repair. A palpable example of this decline is provided by skeletal muscle, a specialized tissue composed of postmitotic myofibers that contract to generate force. Skeletal muscle stem cells (satellite cells) are long-lived and support muscle regeneration throughout life, but at advanced age they fail for largely undefined reasons. Here, we discuss recent advances in the understanding of how satellite cells integrate diverse intrinsic and extrinsic processes to ensure optimal homeostatic function and how this integration is perturbed during aging, causing regenerative failure. With this increased understanding, it is now feasible to design and test interventions that delay satellite cell aging. We discuss the exciting new therapeutic potential of integrating and combining distinct anti-aging strategies for regenerative medicine.
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http://dx.doi.org/10.1016/j.mad.2020.111246DOI Listing
June 2020

Complex Open Pyeloplasty in a Pelvic Kidney.

Urology 2020 Jul 16;141:e47-e48. Epub 2020 Apr 16.

Division of Surgery and Interventional Science, University College London, London, United Kingdom; Specialist centre for kidney cancer, Royal Free Hospital, London, United Kingdom. Electronic address:

A pelvic kidney occurs in between 1 in 2200 and 1 in 3000 people, due to failure of ascent during development. It is commonly asymptomatic and usually functions normally. Pelvic ureteral junction obstruction can either be congenital or acquired, and is characterized by intrinsic stenosis or extrinsic compression of the ureter at the junction with the pelvicalyceal renal system. This can cause symptomatic or asymptomatic hydronephrosis. We describe the complex case and management of a patient with a massive pelvic ureteral junction obstruction in a pelvic kidney.
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http://dx.doi.org/10.1016/j.urology.2020.03.048DOI Listing
July 2020

Outcomes of Renal Tumors Treated by Image-Guided Percutaneous Cryoablation: Immediate and 3- and 5-Year Outcomes at a Regional Center.

AJR Am J Roentgenol 2020 07 14;215(1):242-247. Epub 2020 Apr 14.

Imaging Department, University College London Hospitals NHS Foundation Trust, London, United Kingdom.

The purpose of this study was to evaluate the immediate and 3- and 5-year outcomes of patients with clinical stage T1 (cT1) biopsy-proven renal cell carcinoma (RCC) treated by image-guided percutaneous cryoablation at a regional interventional oncology center. A prospectively maintained local interventional radiology database identified patients with cT1 RCC lesions that were treated by percutaneous cryoablation. Technical success, procedural complications (graded using the Clavien-Dindo classification system), and the residual unablated tumor rate were collated. Local tumor progression-free survival was estimated using Kaplan-Meier estimates. A total of 180 patients with 185 separate cT1 RCC lesions were identified. Mean patient age was 68.4 years (range, 34.1-88.9 years) and 52 patients (28.9%) were women. There were 168 (90.8%) and 17 (9.2%) cT1a and cT1b lesions, respectively, with a mean lesion size of 28.5 mm (range, 11-58 mm). Technical success was achieved in 183 of 185 (98.9%) patients. The major complication rate (Clavien-Dindo classification ≥ grade III) was 2.2% (four out of 185). Residual unablated tumor on the first follow-up scan was identified in four of 183 tumors (2.2%). Estimated local tumor progression-free survival at 3 and 5 years was 98.3% and 94.9%, respectively. No distant metastases or deaths attributable to RCC occurred. Mean estimated glomerular filtration rate (eGFR) before the procedure was 72.4 ± 18.5 (SD) mL/min/1.73 m and this was not statistically significantly different after the procedure (69.7 ± 18.8 mL/min/1.73 m), at 1 year (70.7 ± 16.4 mL/min/1.73 m), or at 2 years (69.8 ± 18.9 mL/min/1.73 m) ( > 0.05). These data add to the accumulating evidence that image-guided cryoablation is an efficacious treatment for selected cT1 RCC with a low complication rate and ro bust 3- and 5-year outcomes.
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http://dx.doi.org/10.2214/AJR.19.22213DOI Listing
July 2020

Hand function and adaptive equipment use in patients with rheumatoid arthritis.

Acta Reumatol Port 2019 Oct-Dec;44(4):273-280

Centro de Reabilitação do Norte.

Objectives: Evaluation and characterization of hand function in patients with rheumatoid (RA) arthritis and, secondarily, identification of the use of adaptive equipments.

Material And Methods: Firstly, a written informed consent was obtained and then an anonymous questionnaire was filled by RA outpatients after observation at the rheumatology consultation with no other musculoskeletal or neuromuscular disorders that would determine major functional impairment of hand function. Sociodemographic and clinical variables were collected and the Cochin Hand Functional Scale (CHFS) was applied. Classical deformities of hand and/or wrist were observed and recorded by the attending physician.

Results: A total of 79 patients were enrolled. In the overall sample, most patients were female A sample of 79 patients, mostly female (69.60%), with a mean age of 59.72 ± 11.77 years and with a mean diagnosis duration of 11.72 ± 8.29 years. The majority (73.40%) had at least one hand or wrist deformity, the most frequent being atrophy of the interosseous muscles followed by ulnar deviation of the metacarpophalangeal joints and piano key deformity of the wrist. The mean CHFS score was 17.94 ± 18.26 points with a minimum and maximum value recorded of 0 and 80 points, respectively. The presence of hand deformities, Health Assessment Questionnaire score (HAQ), hand pain and diagnosis duration were correlated with the CHFS score. Six patients had assistive devices and only in one case it was used to overcome hand's functional impairment.

Conclusions: Most patients presented at least one classic RA deformity after a mean diagnosis duration of approximately 12 years and under pharmacological treatment. Despite this, most patients scored significantly below CHFS maximum score, but only 18 reported no difficulty in any of the tasks mentioned in the scale. The fact that only a minority of these patients had assistive devices should alerts us to the need for a more thorough functional assessment and identification of needs among RA patients.
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October 2020

Aging eyes and the immune system.

Authors:
Joana Neves

Science 2020 Mar;367(6483):1205-1206

Instituto de Medicina Molecular (iMM), Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

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http://dx.doi.org/10.1126/science.aba6114DOI Listing
March 2020

MANF delivery improves retinal homeostasis and cell replacement therapies in ageing mice.

Exp Gerontol 2020 Feb 28;134:110893. Epub 2020 Feb 28.

Paul F. Glenn Center for Biology of Aging Research, Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Ophthalmology, University of California, San Francisco, SF, USA. Electronic address:

Ageing is a major risk factor for vision loss, and inflammation is an important contributor to retinal disease in the elderly. Regenerative medicine based on cell replacement strategies has emerged in recent years as a promising approach to restore vision. However, how the ageing process affects retinal homeostasis and inflammation in the retina and how this may impose a limitation to the success of such interventions remains unknown. Here we report that, in mice and humans, retinal ageing is associated with a reduction in MANF protein levels, specifically in the choroid, where increased densities of activated macrophages can be detected. We further show that the retina of old wild type mice, in the absence of any other genetic alteration, has limited homeostatic capacity after damage imposed by light exposure and reduced engraftment efficiency of exogenously supplied photoreceptors. Finally, we show that supplementation of MANF recombinant protein can improve retinal homeostasis and repair capacity in both settings, correlating with reduced numbers of activated macrophages in the old retina. Our work identifies age-related alterations in retinal homeostasis, independent of genetic alterations, leading to age-related retinal inflammation and damage susceptibility. We suggest that MANF therapy is a potential intervention to maintain retinal homeostasis in the elderly and improve the success of retinal regenerative therapies applied to aged individuals.
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http://dx.doi.org/10.1016/j.exger.2020.110893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483617PMC
February 2020