Search

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Background Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown. Methods We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated. Results We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS. Conclusion We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results. pre-print 728 KB

682 Background: Localized and oligometastatic resectable renal cell carcinoma (RCC) have moderate to high rates of relapse after surgery and evidence regarding the efficacy of perioperative treatments is conflicting. The risk of relapse varies across studies and there is a need to define the benefit/risk of immune checkpoint inhibitors (ICI) in this setting to optimize their use. Methods: A meta-analysis of the randomized phase 3 trials of peri-operative treatment with anti-PD-1/PD-L1 agents or anti-PD1/antiCTL4 in combination was conducted. The primary outcomes of interest were disease-free survival (DFS) and overall survival (OS). Secondary outcomes of interest were the proportion of grade 3-4 adverse events (AE) according to CTCAE 5.0. Subgroup analyses were performed according to clinically relevant characteristics. Statistical heterogeneity assumption was evaluated by the χ²-based Cochran’s Q test and quantified with the I² statistic. All statistical analyses were performed using Stata software (StataCorp LLC), version 16. Results: Published results of 4 phase 3 trials were included, involving 3393 patients. 1695 patients received ICI (anti-PD1: 900 patients; anti-PD-L1 390 patients, antiPD1/anti-CTLA4 405 patients) while 1712 received no active treatment (1297 placebo, 415 observation). ICI did not show to increase DFS (Hazard ratio (HR) 0.84 95% CI 0.69-1.03 p 0.10) or OS (HR 0.73 95% CI 0.40-1.34 p 0.31). High-grade AEs were 2.6 times more frequent in the immunotherapy arm (OR 2.64 95% CI 1.54 – 4.68 p < 0.001) while high grade treatment-related AEs were 8 times more frequent in the experimental arm (OR 8.60 95% CI 3.23-22.91 p < 0.001). Interestingly, subgroup analyses showed statistically significant differences favoring the experimental arm in females (HR 0.72 95% CI 0.55-0.93 p 0.01), in patients with sarcomatoid differentiation (HR 0.59 95% CI 0.403-0.88 p 0.010) and PD-L1 positive tumors (HR 0.74 95% CI 0.61-0.90 p 0.003). No significant effect was found in patients according to age, type of nephrectomy (radical vs. partial), and stage (M1 without evidence of disease vs M0 patients). Conclusions: The introduction of anti-PD-(L)1 +/- anti-CTLA-4 agents in the adjuvant setting of RCC might benefit selected RCC patients, although with increased toxicity. Longer follow-up of the conducted studies is needed to establish a potential benefit in long-term survival.

Neonatal diseases differ depending on gestational age and weight. In the setting of an emergency in the neonatal intensive care unit (NICU), relevant clinical information is often not available when the first neonatal radiograph is obtained. When reading an initial chest-abdomen radiograph, the paediatric radiologist needs gestational age data for best radiologic practice. A transverse diameter of the chest has been previously described to estimate gestational age (GA).To determine the strength of the correlation between GA/weight and clavicular-pubis length (CPL) on admission radiographs; to obtain a quadratic formula based on the correlation of CPL with GA and to demonstrate if a more simplified formula used by our group works as efficiently as the formula provided by the regression analysis.A retrospective study was approved by the institutional review board and informed consent was waived. The length from the medial aspect of the clavicle to the pubic bone was measured on the initial portable chest-abdomen radiographs of 260 patients admitted to the NICU in 2016. Regression analysis was performed to investigate the association between CPL and GA/birth weight.One hundred eleven females and 149 males with GA between 23 and 42 weeks were evaluated. CPL was statistically associated with both GA (P0,01) and birth weight. The estimation can be expressed with an equation of the model: GA (weeks) = (CPL in cm - 1.98)/0.42. A simplified formula: GA (weeks) = (CPL in cm) ×2+2, strongly correlates with the equation model.In patients in whom it is not known, GA can be estimated by measuring the length between medial clavicle and symphysis pubis using the formulae we propose.

Objective:To determine the association between ultra-processed food (UPF) intake and all-cause mortality in a representative sample of Spanish population.Design:Prospective cohort design in which follow-up lasted from baseline (1991) to mortality date or 31 December 2017, whichever was first. Dietary information was collected using a validated frequency questionnaire and categorised following the NOVA classification according to the extent of food processing. The association between consumption of UPF and mortality was analysed using Cox models. Isoenergetic substitution models were constructed to compare the health effects of the NOVA groups.Setting:Cohort from the Diet and Risk of Cardiovascular Diseases (CVD) in Spain (DRECE) study, representative of the Spanish populationParticipants:Totally, 4679 subjects between 5 and 59 years old.Results:Average consumption of UPF was 370·8 g/d (24·4 % of energy intake). After a median follow-up of 27 years, 450 deaths occurred. Those who consumed the highest amount of UPF had higher risk of mortality. For every 10 % of the energy intake from UPF consumption, an increase of 15 % in the hazard of all-cause mortality was observed (HR 1·15; (95 % CI 1·03, 1·27); P-value = 0·012). Substitution of UPF with minimally processed foods was significantly associated with a decreased risk of mortality.Conclusions:An increase in UPF consumption was associated with higher risk of all-cause mortality in a representative sample of the Spanish population. Moreover, the theoretical substitution of UPF with unprocessed or minimally processed foods leads to a decrease in mortality. These results support the need to promote diets based on unprocessed or minimally processed foods.

To investigate whether physical activity (PA) is a protective factor for the incidence of Parkinson’s disease (PD) and parkinsonism after three years of follow-up. All participants of this study were obtained from the Neurological Disorders in Central Spain (NEDICES), a prospective population-based cohort survey of older subjects (≥65 years) that comprised 5278 census-based participants at baseline (1994–1995). A modified version of Rosow-Breslau questionnaire was applied to categorize PA into active versus sedentary group. The final diagnosis of PD and parkinsonism was made by an expert neurologist. Cox regression models (CRM) adjusted for several covariates (sex, age, education, alcohol consumption, tobacco, stroke, hypertension and body mass index) were used to calculate the association between PA (active group vs. sedentary) and risk of PD and parkinsonism after three years. 22 incident PD and 25 incident parkinsonism cases were identified among 2943 participants with available PA information (57.1% female; mean age = 73.28 ± 6.24 years) after three years of follow-up. The CRM showed that the active group (vs. sedentary) showed a lower risk of parkinsonism (Hazard ratio (HR) = 0.18; 95% CI [0.07–0.51]; p = 0.0001). However, this effect was restricted to men (HR = 0.34; 95% CI [0.11–0.99], p

Front-of-pack labels can improve the ability of consumers to identify which foods are healthier, making them a useful public health tool. Nutri-Score is a front-of-pack labelling system adopted by several European countries. This system ranks foods according to their nutritional quality, but does not consider other dimensions such as the degree of food processing. The aim of this study is to compare the nutritional quality (as assessed by Nutri-Score) and the ultra-processing (as assessed by the NOVA classification) of foods in the Open Food Facts database. A simple correspondence analysis was carried out to study the relationship between the two systems. Ultra-processed foods (NOVA 4) were found in all Nutri-Score categories, ranging from 26.08% in nutritional category A, 51.48% in category B, 59.09% in category C, 67.39% in category D to up to 83.69% in nutritional category E. Given the negative effect that the consumption of ultra-processed foods has on different aspects of health, front-of-pack labelling with Nutri-Score should at least be accompanied by complementary labelling indicating the level of processing, such as the NOVA classification.

Purpose Fumarate hydratase–deficient (FHdef) renal cell carcinoma (RCC) is a rare entity associated with the hereditary leiomyomatosis and RCC syndrome with no standard therapy approved. The aim of this retrospective study was to evaluate the efficacy of different systemic treatments in this population. Methods We performed a multicentre retrospective analysis of Fhdef RCC patients to determine the response to systemic treatments. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and overall survival (OS). The two latter were estimated using the Kaplan–Meier method. Results Twenty-four Fhdef RCC patients were identified, and 21 under systemic therapy were included in the analysis: ten received cabozantinib, 14 received sunitinib, nine received “other antiangiogenics” (sorafenib, pazopanib, and axitinib), three received erlotinib-bevacizumab (E-B), three received mTOR inhibitors, and 11 received immune checkpoint blockers (ICBs). ORR for treatments were 50% for cabozantinib, 43% for sunitinib, 63% for “other antiangiogenics,” and 30% for E-B, whereas ORR was 0% for mTOR inhibitors and 18% for ICBs. The median TTF (mTTF) was significantly higher with antiangiogenics (11.6 months) than with mTOR inhibitors (4.4 months) or ICBs (2.7 months). In the first-line setting, antiangiogenics presented a higher ORR compared with nivolumab-ipilimumab (64% versus 25%) and a significantly superior mTTF (11.0 months vs 2.5 months; p = 0.0027). The median OS from the start of the first systemic treatment was 44.0 months (95% confidence interval: 13.0–95.0). Conclusions We report the first European retrospective study of Fhdef RCC patients treated with systemic therapy with a remarkably long median OS of 44.0 months. Our results suggest that antiangiogenics may be superior to ICB/mTOR inhibitors in this population.

320 Background: Immune checkpoint combination therapy (ICI-combo) is the new standard of care for mRCC in first-line setting. However, pts with poor PS (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-combo in this group of pts is still unknown. Methods: We performed a multicentre retrospective study of PS≥2 mRCC pts who received ICI-combo, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (PA) as first-line treatment between 2017-2021. Patient’s characteristics, clinical outcomes and toxicity were retrospectively reviewed. We analysed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and grade ≥3 treatment-related adverse events (G≥3 AEs) in pts treated with NI or PA. The association between LIPI (Lung Immune Prognostic Index) and ORR, PFS and OS was also evaluated. Results: We identified 56 mRCC pts with PS≥2 treated with ICI-combo across 13 institutions. Thirty-six and 20 pts were treated with NI and PA respectively. Median age at diagnosis was 64 (31-83) years, 38 (68%) were male, 16 (29%) had prior nephrectomy and 40 (71%) had synchronous metastatic disease at diagnosis. Respectively, 19 (34%) and 37 (66%) pts were intermediate and poor risk according to IMDC. Fifty pts (89%) were clear cell RCC, and only 4 pts had sarcomatoid features reported. At the time of analysis (median follow-up 11.1 months(mo)) 45% pts were dead. The ORR for the entire cohort was 27%; ORR was numerically higher with PA (42%) than with NI (20%) but did not reach statistical significancy (p=0.157). Median PFS (mPFS) and mOS in the entire cohort were 4.4 mo and 15.9 mo respectively. No significant differences in PFS, OS or the rate of G≥3AEs were seen between the NI and PA groups. Efficacy and toxicity outcomes are described in the table below. No significant differences in OS or PFS according to the IMDC risk score were observed (p=0.818). However, LIPI was significantly associated with OS (poor LIPI: HR=8.18; p=0.004) and PFS (Intermediate LIPI: HR=2.4; p=0.048 and poor LIPI: HR=8.59; p