Impact of worsening surgically induced chronic kidney disease (CKD-S) in preoperative CKD-naïve patients on survival in renal cell carcinoma.

OBJECTIVES: To evaluate effects of worsening surgically induced chronic kidney disease (CKD-S) on oncological and non-oncological survival outcomes in renal cell carcinoma (RCC). PATIENTS AND METHODS: We performed a retrospective analysis of patients who underwent partial (PN) or radical nephrectomy (RN) and were free of preoperative CKD (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 ). Patients were stratified by CKD stage at last follow-up: no CKD-S (eGFR ≥60 mL/min/1.73 m2 ), de novo CKD-S 3a (eGFR 45-59 mL/min/1.73 m2 ), CKD-S 3b (eGFR <45 and ≥30 mL/min/1.73 m2 ) and CKD-S 4 (eGFR <30 and ≥15 mL/min/1.73 m2 ). The primary outcome was all-cause mortality (ACM). Secondary outcomes included non-cancer mortality (NCM), cancer-specific mortality (CSM) and de novo CKD-S Stage 3/4. Multivariable analysis (MVA) was utilised to identify risk factors for outcomes. Kaplan-Meier analysis (KMA) was utilised to evaluate overall (OS), non-cancer (NCS), and cancer-specific survival with respect to CKD-S categories. RESULTS: We analysed 3239 patients. The mean preoperative and last-follow-up eGFRs were 87.4 and 69.5 mL/min/1.73 m2 , respectively. On last follow-up, 57.9% (n = 1876) had no CKD-S, 18.7% (n = 606) had CKD-S 3a, 15.1% (n = 489) had CKD-S 3b and 8.3% (n = 268) had CKD-S 4. On MVA, de novo CKD-S 3b and 4 were independently associated with ACM (hazard ratios [HRs] 1.3-2.1, P = 0.003-0.001) and NCM (HRs 1.5-2.8, P = 0.021-0.001), but not CSM (P = 0.219-0.909); de novo CKD-S 3a was not predictive for any mortality outcomes (P = 0.102-0.81). RN was independently associated with CKD-S 3-4 (HRs 1.78-1.99, P < 0.001-0.035). Comparing no CKD-S, CKD-S 3a, CKD-S 3b and CKD-S 4, KMA demonstrated worsening outcomes with progressive CKD-S stage: 5-year OS 84% vs 78% vs 71% vs 60% (P < 0.001) and 5-year NCS 93% vs 87% vs 83% vs 72% (P < 0.001). CONCLUSION: Development of CKD-S Stage 3b and 4, but not 3a, was associated with worsened ACM and NCM. The decision to proceed with nephron preservation via PN should be individualised based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3a.

Assessing the Trade-off Between the Safety and Effectiveness of Off-clamp Robotic Partial Nephrectomy for Renal Masses with a High RENAL Score: A Propensity Score-matched Comparison of Perioperative and Functional Outcomes in a Multicenter Analysis.

BACKGROUND: Tumors with a high nephrometry score represent a challenging surgical scenario for which robotic partial nephrectomy (RPN) is a primary option in expert hands. OBJECTIVE: To compare perioperative and functional outcomes of off-clamp and on-clamp RPN in patients with renal masses with a high RENAL score (≥9). DESIGN, SETTING, AND PARTICIPANTS: For this retrospective analysis, an RPN data set including 1604 patients treated at three institutions between 2003 and 2021 was queried for cases with a RENAL score ≥9. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used 1:1 propensity score matching (PSM) to select a cohort in which imbalances between the off-clamp and on-clamp groups were minimized. We used χ2 and Student t tests to compare categorical and continuous variables, respectively. The Kaplan-Meier method was used to compare the probability of having an estimated glomerular filtration rate (eGFR) ≥45 ml/min during follow-up. Univariable and multivariable analyses were performed to identify predictors of a trifecta outcome (negative surgical margin status, no Clavien-Dindo grade ≥3 complications, eGFR decline ≤30%) and of retaining eGFR ≥45 ml/min over time. RESULTS AND LIMITATIONS: From an overall cohort of 354 patients (142 on-clamp, 212 off-clamp), a homogeneous PSM cohort of 78 patients in each group was selected (p ≥ 0.17). In the PSM cohort, operative time was significantly shorter in the off-clamp group (p < 0.001). There were no differences between the groups in the rates of severe complications (p = 0.32) and positive surgical margins (p = 0.24). The rate of trifecta achievement was significantly higher in the off-clamp group (83.3% vs 67.9%; p = 0.03). Warm ischemia time >20 min was independently negatively associated with trifecta achievement (odds ratio 0.32, 95% confidence interval 0.14-0.74). Moreover, the off-clamp group had a significantly higher probability of retaining eGFR ≥45 ml/min over time (3 yr: 95.9% vs 81.6%; p = 0.03); every 1-min increase in warm ischemia time reduced this probability by 1.3%. CONCLUSIONS: We found a favorable trade-off between the benefits and risks of off-clamp RPN, with similar perioperative outcomes and a net benefit in terms of trifecta achievement and long-term renal function outcomes in comparison to on-clamp RPN. PATIENT SUMMARY: The complexity of surgery for kidney tumors can be assessed using the RENAL score, which is a measure of the location and size of a kidney tumor. In a multicenter series of patients with tumors with a high RENAL score, we compared outcomes between strategies with (on-clamp) and without (off-clamp) clamping of kidney blood vessels during robot-assisted removal of part of the affected kidney. We found that off-clamp surgery results in better postoperative kidney function.

Imbalance Between Omega-6- and Omega-3-Derived Bioactive Lipids in Arthritis in Older Adults.

Elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) are common rheumatic diseases in older adults. Oxylipins are bioactive lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) that serve as activators or suppressors of systemic inflammation. We hypothesized that arthritis symptoms in older adults were related to oxylipin-related perturbations. Arthritis in older adults (ARTIEL) is an observational prospective cohort with 64 patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples at baseline and 3 months posttreatment were compared with 18 controls. A thorough clinical examination was conducted. Serum oxylipins were determined by mass spectrometry. Data processing and statistical analysis were performed in R. Forty-four patients were diagnosed with EORA and 20 with PMR. At diagnosis, EORA patients had a mean DAS28CRP (Disease Activity Score 28 using C-reactive protein) of 5.77 (SD 1.02). One hundred percent of PMR patients reported shoulder pain and 90% reported pelvic pain. Several n-6- and n-3-derived oxylipin species were significantly different between controls and arthritis patients. The ratio of n-3/n-6 PUFA was significantly downregulated in EORA but not in PMR patients as compared to controls. The top two candidates as biomarkers for differentiating PMR from EORA were 4-HDoHE, a hydroxydocosahexaenoic acid, and 8,15-dihydroxy-eicosatrienoic acid (8,15-diHETE). The levels of n-3-derived anti-inflammatory species increased in EORA after treatment. These results suggest that certain oxylipins may be key effectors in arthrtis in older adults and that the imbalance between n-6- and n-3-derived oxylipins might be related to pathobiology in this population.

Evaluation of the association of health care system access with kidney cancer surgical outcomes for hispanic and non-hispanic white patients.

OBJECTIVE: To determine the impact of health care system access on outcomes for Hispanic and Non-Hispanic White patients with renal cell carcinoma (RCC). METHODS: We retrospectively analyzed Hispanic and non-Hispanic White patients diagnosed with localized RCC between 2007 and 2020. We used Health Resources and Services Administration criteria to identify patients living in Medically Underserved Areas (MUA). Primary outcome all-cause mortality and cancer-specific survival using Log Rank test on Kaplan Meier Analysis. Secondary outcome was all-cause mortality and cancer specific survival on Cox Regression when adjusting for risk factors. RESULTS: We analyzed 774 patients, 246 (31.8%) Hispanic patients and 528 (68.2%) Non-Hispanic White patients. Hispanic ethnicity was associated with lower risk of ACM (HR 0.53, P = 0.019) and there was no difference for cancer specific survival (HR 0.57, P = 0.059). Living in a MUA was associated with worse all-cause mortality (P = 0.010) but not cancer specific survival (CSS) (P = 0.169). Comparing Hispanic and Non-Hispanic Whites, KMA revealed no difference in 5-year all-cause mortality (83.1% vs. 78.8%, P = 0.254) and 5-year CSS (85.7% vs. 85.4%, P = 0.403). CONCLUSIONS: Hispanics had lower all-cause mortality risk and no significant differences in 5-year overall survival and CSS compared to non-Hispanic Whites. Our findings indicate that tertiary referral centers may help mitigate inequalities in access to care.

Design of an anti-inflammatory diet (ITIS diet) for patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved treatment of RA, patients with RA often inquire about dietary interventions to improve RA symptoms, as they perceive rapid changes in their symptoms after consumption of certain foods. There is evidence that some ingredients have pro- or anti-inflammatory effects. In addition, recent literature has shown a link between diet and microbiome changes. Both diet and the gut microbiome are linked to circulating metabolites that may modulate inflammation. However, evidence of the effects of an anti-inflammatory and probiotic-rich diet in patients with RA is scarce. There is also a need for biological data to support its anti-inflammatory effects. METHODS: The main goal of this study is to delineate the design process for a diet tailored to our RA population. To achieve this goal, we collected information on diet, supplements, cooking methods, and intake of different ingredients for each patient. Different groups were interviewed, and their feedback was assessed to design a diet that incorporates suggested anti-inflammatory ingredients in a manner that was easy for patients to adopt based on their lifestyles and backgrounds. RESULTS: We designed a diet that includes a high intake of potential anti-inflammatory ingredients. Feedback from highly motivated patients was critical in constructing an anti-inflammatory diet (ITIS diet) with elevated adherence. CONCLUSION: In order to tailor our diet, we surveyed our patients on several different parameters. We obtained important feedback on how feasible our ITIS diet is for RA patients. Using this feedback, we made minor improvements and finalized the design of the ITIS diet. This diet is being used in an on-going pilot study to determine their anti-inflammatory effect in pain and joint swelling in RA patients. TRIAL REGISTRATION: Not applicable.

Liquid biopsies to guide therapeutic decisions in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that has transitioned from a debilitating disease to a chronic, controllable disease. This has been possible due to the introduction of new treatment strategies like "treat-to-target," in which the clinician treats the patient aggressively enough to reach low disease activity or remission, and the introduction of new therapeutic agents, such as biological therapies, which can lead to the prevention of damage by early diagnosis and initiation of treatment. Attention is now being directed toward identifying the optimal treatment for each patient, one that will be the most efficient and have the least number of side effects. Much work has been done to find serologic and synovial biomarkers of response to various RA treatments. Proteomics, genomics and, in the past few years, metabolomics, have all been used in the quest of identifying these biomarkers. Blood-based liquid biopsies provide a minimally invasive alternative to synovial biopsies to identify cellular and molecular signatures that can be used to longitudinally monitor response and allow for personalized medicine approach. Liquid biopsies are comprised of cell-free DNA, immune circulating cells, and extracellular vesicles, and are being increasingly and successfully used in the field of oncology for diagnosis, progression, prognosis, and prediction of response to treatment. Recently, researchers have also begun investigating the usefulness of liquid biopsies in the field of rheumatology; in this review, we will focus on the potential of liquid biopsy blood samples as biomarkers of response to treatment in patients with RA.

Serum metabolomic profiling predicts synovial gene expression in rheumatoid arthritis.

BACKGROUND: Metabolomics is an emerging field of biomedical research that may offer a better understanding of the mechanisms of underlying conditions including inflammatory arthritis. Perturbations caused by inflamed synovial tissue can lead to correlated changes in concentrations of certain metabolites in the synovium and thereby function as potential biomarkers in blood. Here, we explore the hypothesis of whether characterization of patients' metabolomic profiles in blood, utilizing 1H-nuclear magnetic resonance (NMR), predicts synovial marker profiling in rheumatoid arthritis (RA). METHODS: Nineteen active, seropositive patients with RA, on concomitant methotrexate, were studied. One of the involved joints was a knee or a wrist appropriate for arthroscopy. A Bruker Avance 700 MHz spectrometer was used to acquire NMR spectra of serum samples. Gene expression in synovial tissue obtained by arthroscopy was analyzed by real-time PCR. Data processing and statistical analysis were performed in Python and SPSS. RESULTS: Analysis of the relationships between each synovial marker-metabolite pair using linear regression and controlling for age and gender revealed significant clustering within the data. We observed an association of serine/glycine/phenylalanine metabolism and aminoacyl-tRNA biosynthesis with lymphoid cell gene signature. Alanine/aspartate/glutamate metabolism and choline-derived metabolites correlated with TNF-α synovial expression. Circulating ketone bodies were associated with gene expression of synovial metalloproteinases. Discriminant analysis identified serum metabolites that classified patients according to their synovial marker levels. CONCLUSION: The relationship between serum metabolite profiles and synovial biomarker profiling suggests that NMR may be a promising tool for predicting specific pathogenic pathways in the inflamed synovium of patients with RA.