190 research outputs found
Posterior Urethral Valves, Unilateral Vesicoureteral Reflux, and Renal Dysplasia (VURD) Syndrome: Long-Term Longitudinal Evaluation of the Kidney Function
No full textThe presence of unilateral vesicoureteral reflux (VUR), and renal dysplasia associated with posterior urethral valves (PUV) (VURD syndrome) was believed to represent a pressure-released pop-off mechanism protecting kidney function. We aimed to investigate its role with respect to long-term kidney function in a cross-sectional and longitudinal analysis. We compared the iohexol glomerular filtration rate (GFR) measured at 5 (GFR5) and 10 (GFR10) years of age in children with (Group A) and without (Group B) VURD syndrome, who underwent PUV resection under 2 years of age. VURD syndrome was diagnosed in cases of unilateral loss of kidney function (<15% on nuclear medicine test) associated with ipsilateral grade IV-V VUR. VURD syndrome was diagnosed in 16 (12.8%) out of 125 patients who met the inclusion criteria. While the median GFR5 was similar in the 2 groups [Group A: 87.3 (74.7–101.2) mL/min/1.73 m2 vs. Group B: 99.6 (77–113) mL/min/1.73 m2, p-value: 0.181], the median GFR10 values were significantly lower in children with VURD syndrome [Group A: 75.7 (71.2–85.9) mL/min/1.73 m2 vs. Group B: 95.1 (81.2–114.2) mL/min/1.73 m2, p-value: 0.009]. Similar results were obtained in a longitudinal analysis of the children with GFR measurement available both at 5 and 10 years of age [GFR5 in Group A: 93.1 (76.9–103.5) mL/min/1.73 m2 vs. Group B: 97.5 (80–113) mL/min/1.73 m2, p-value: 0.460; GFR10: Group A: 71.9 (71.9–85.9) mL/min/1.73 m2 vs. Group B: 94.8 (81.5–110.6) mL/min/1.73 m2, p-value: 0.024]. In conclusion, VURD syndrome does not show a protective role in kidney function preservation. On the contrary, it seems to be associated with a deterioration of the kidney function on a long-term follow-up
Prevalence of Mitral Valve Prolapse Among Individuals with Pectus Excavatum: A Systematic Review and Meta-Analysis
No full textBackground: During the last decades, a small number of studies reported a wide range of variability in the estimated prevalence of mitral valve prolapse (MVP) among individuals with pectus excavatum (PE). The present systematic review and meta-analysis has been primarily designed to summarize the main findings of these studies and to estimate the overall prevalence of MVP among PE individuals. Methods: All imaging studies assessing the prevalence of MVP in PE individuals vs. healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case–Control Studies. Events (presence of MVP) and nonevents (absence of MVP) in PE individuals and control groups were recorded. The main outcome was the measure of odds ratio (OR) for MVP presence pooled with 95% confidence intervals, using a fixed-effects model. Results: The full texts of eight studies with 303 PE patients (mean age 25.7 yrs) and 498 healthy controls (mean age 31 yrs) were analyzed. Three studies assessed MVP prevalence in children and early adolescents, whereas the remaining five studies examined PE adults. The prevalence of MVP in PE individuals and healthy controls was 40.6% and 12.8%, respectively. In the pooled sample, the OR for MVP presence was significantly higher in PE individuals compared to controls (OR = 5.80, 95%CI = 3.83–8.78, Z = 8.30, p < 0.001). Subgroup analysis revealed that MVP prevalence was approximately three-fold higher among PE children and early adolescents compared with PE adults. Overall, high consistency was observed in the pooled effect sizes, due to the low statistical heterogeneity among the included studies (I2 = 22.7%, p = 0.25). Egger’s test for a regression intercept gave a p-value of 0.07, indicating no publication bias. The sensitivity analysis supported the robustness of the results. Conclusions: PE individuals are nearly six times more likely to have MVP than controls. MVP prevalence is three-fold higher in PE individuals during childhood and early adolescence, compared to PE adults. Given the strong association between MVP and PE, MVP should be suspected in all individuals with anterior chest wall deformity
0986 Tasimelteon Improves Symptoms of Major Depression in an African American Population
No full text2014P Overall survival (OS) results in phase II trial of cabozantinib (CABO) plus durvalumab (DURVA) in patients with urothelial carcinoma (UC) or non-UC variant histologies (VH) after platinum chemotherapy (ARCADIA)
No full textBackground
Combining multitargeted receptor tyrosine kinase inhibitor (TKI) with checkpoint inhibitors has shown synergistic effect in pts with in various solid tumors due to the immunomodulatory propriety of VEGFR inhibitors. We aim to investigate the safety and efficacy of the combination of cabozantinib plus durvalumab in advanced UC and VHs (NCT03824691). Herein we present the overall survival results of the interim analysis.
Methods
Patients affected by UC or non-urothelial carcinoma (VHs) recurred/progressed after at least one line of platinum-based chemotherapy for metastatic disease have been treated with CABO 40 mg daily, orally, and DURVA 1500 mg IV, q28 days, until disease progression (PD, by RECIST 1.1) or onset of unacceptable toxicity. Response was evaluated by RECIST criteria v.1.1 every 8 wks. The primary endpoint of the study was OS. Secondary endpoints included safety (CTCAE v.4.03), objective response-rate (ORR), duration of response (DoR), progression-free survival (PFS).
Results
As of February 10, 2024 data cut, 61 pts were enrolled and were evaluable for response; median follow-up was 26 months (interquartile 16.38-35.82), median age was 64 yrs and 21 pts (24%) had pure/predominant VHs: 10 (47.6%) squamous differentiation/sarcomatoid tumor, 4 (19%) adenocarcinoma, 5 (24%) small-cell neuroendocrine tumor, 1 (4.7%) clear-cell tumor, and 1 nested VH (4.7%). 12/61 (20% liver mets.12 pts (20%) had ≥ 2 prior lines of therapies. Median OS and PFS were 12.9 months (95% CI, 7.1-25.5) and 6 months (95% CI, 3.9-9.4), respectively. Confirmed ORR was 42.6% (range 30-55.9),18% CR in 11 pts. For VHs subgroup, median OS and PFS were 17.6 months (95% CI, 5.3-NR), and 5.3 (95% CI, 2.8-NR), respectively and ORR was 31%. At analysis, 9 pts remained on treatment. 2/61(3%) pts received EV as subsequent therapy. 38/61 pts had treatment-related adverse events of any grade and 25 (41%) had grade 3/4.
Conclusions
CABO in combination with DURVA suggests promising prolonged survival and acceptable tolerability in pts with advanced UC, especially those with VHs. Further randomized controlled studies will be required in a larger patient population.
Clinical trial identification
NCT03824691
Overall survival (OS) results in phase II Trial of Cabozantinib (CABO) plus durvalumab (DURVA) in patients with urothelial carcinoma (UC) or non- UC variant histologies (VH) after platinum chemotherapy (ARCADIA).
No full textBackground: Combining multitargeted receptor tyrosine kinase inhibitor (TKI) with checkpoint inhibitors has shown synergistic effect in pts with in various solid tumors due to the immunomodulatory propriety of VEGFR inhibitors.
We aim to investigate the safety and efficacy of the combination of cabozantinib plus durvalumab in advanced
UC and VHs (NCT03824691). Herein we present the overall survival results of the interim analysis.
Methods: Patients affected by UC or non-urothelial carcinoma (VHs) recurred/progressed after at least one line of platinum-based chemotherapy for metastatic disease have been treated with CABO 40 mg daily, orally, and DURVA 1500 mg IV, q28 days, until disease progression (PD, by RECIST 1.1) or onset of unacceptable toxicity. Response was evaluated by RECIST criteria v.1.1 every 8 wks. The primary endpoint of the study was OS. Secondary endpoints included safety (CTCAE v.4.03), objective response-rate (ORR), duration of response (DoR), progression-free survival (PFS).
Results: As of February 10, 2024 data cut, 61 pts were enrolled and were evaluable for response; median followup
was 26 months (interquartile 16.38-35.82), median age was 64 yrs and 21 pts (24%) had pure/predominant VHs: 10 (47.6%) squamous differentiation/sarcomatoid tumor, 4 (19%) adenocarcinoma, 5 (24%) small-cell neuroendocrine
tumor, 1 (4.7%) clear-cell tumor, and 1 nested VH (4.7%). 12/61 (20% liver mets.12 pts (20%) had ≥ 2 prior lines of therapies. Median OS and PFS were 12.9 months (95% CI, 7.1-25.5) and 6 months (95% CI, 3.9-9.4), respectively. Confirmed ORR was 42.6% (range 30-55.9),18% CR in 11 pts. For VHs subgroup, median OS and PFS were 17.6 months (95% CI, 5.3-NR), and 5.3 (95% CI, 2.8-NR), respectively and ORR was 31%. At analysis, 9 pts remained on treatment. 2/61(3%) pts received EV as subsequent therapy. 38/61 pts had treatment- related adverse events of any grade and 25 (41%) had grade 3/4.
Conclusions: CABO in combination with DURVA suggests promising prolonged survival and acceptable tolerability
in pts with advanced UC, especially those with VHs. Further randomized controlled studies will be required in a
larger patient population
1981P Cabozantinib plus durvalumab in patients with advanced and chemotherapy-treated urothelial carcinoma (UC) and variant histology (VH): An open-label, phase II, single-arm proof-of-concept trial: ARCADIA study. Subgroup analysis for bone metastasis
No full textBackground
Preliminary results from the phase II ARCADIA trial (NCT03824691) showed promising activity of cabozantinib (CABO) in combination with durvalumab (DURVA) in patients with advanced or metastatic UC and in non-UC VH after previous chemotherapy exposure. Herein we report the preliminary results of the subgroup analysis for Bone metastasis (BM).
Methods
Patients affected by UC and VHs recurred or progressed after failure of at least one line of platinum-based chemotherapy have been treated with CABO 40 mg daily, orally, and are administered DURVA 1500 mg IV, q28 days, until disease progression (PD), by RECIST v.1.1, or onset of unacceptable toxicity. Response was evaluated by RECIST criteria v.1.1 every 8 weeks and by EORTC PET response criteria by 18FDG PET/CT scan. The primary endpoint of the study was OS whereas secondary endpoints included FDG-PET responses in BM.
Results
Between September 2019 and April 2024, the ARCADIA study enrolled 88 patients: this interim analysis was performed after obtaining at least one post-baseline tumor assessment data from 61 patients. The median follow-up was 26.8 mo (95%CI 19.4-39.2). 22/61 (36%) patients had BM. Patients were evaluated with 18FDG PET/CT scan and CT scan. Complete Metabolic Response was described in 4/22 (18%) patients, Partial Metabolic Response in 3/22 (13.6%), Stable Metabolic Disease in 2/22 (9%) patients whereas 4/22 (18%) patients had Progressive Metabolic Disease as best response. 9/25 (36%) patients experienced disease clinical progression after the 2nd doses of study intervention. mPFS was 4.7 months (95%CI 2.0-7.0) whereas mOS was 6.7 (95%CI 5.1-NR). Smoking habit, liver metastasis, ECOG PS, line of tratment ARCADIA trial, WBC, LDH and AEs were significantly associated with OS in patients with BM. 4/22 (18%) received Bone Target Agents concomitantly and SREs were described in 11/22 (50%).
Conclusions
CABO-DURVA has activity in pretreated, platinum-refractory mUC patients with BM with interesting results in term of metabolic response. More mature results including larger sample of BM patients and with longer follow-up are awaited.
Clinical trial identification
NCT03824691
Mutation in the -Synuclein Gene Identified in Families with Parkinson's Disease
No full textParkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder
Phylogenetic analysis of the allometry of metabolic rate and mitochondrial basal proton leak.
No full textThe mitochondrial basal proton leak (MBPL) significantly contributes to high body temperatures (T b) and basal metabolic rates (BMR) in endotherms. In endotherms at a given body mass (M), liver MBPL is higher than in ectotherms, supporting the notion that MBPL may partly explain the evolutionary increase in metabolic rate (MR), fostering endothermy. Here, we re-addressed this assumption by performing a phylogenetic analysis comparing all available liver MBPL data for ecto- and endotherms. While MBPL within endotherms negatively scales with M and BMR as shown previously, MBPL of ectotherms does not scale allometrically with M. Phylogenetic analysis reveals that this result is confounded by a positive scaling coefficient for MBPL with M for reptiles. Strikingly, the reptilian MBPL reaches endothermic levels above a body mass of 6.6kg. Thus, phylogenetic scaling of MBPL supports previous claims of endotherm-like physiological characteristics in large reptiles. It appears that diversification of ancestral ectothermic tetrapods to a body mass of at least 6kg may have been required to reach a MBPL that is beneficial for sustained high body temperatures. Novel MBPL data for the lesser hedgehog tenrec, a protoendothermic eutherian that displays reptile-like thermoregulatory patterns, fall within the endo- and ectothermic allometric regressions. Finally, we add additional evidence that within endotherms, phylogenetic differences in MR do not correlate with MBPL. Collectively, these data suggest that MBPL does not universally scale with metabolic rate in ecto- or endotherms and that an increasing MBPL with M may have played an important physiological role in the evolutionary history of reptilian thermoregulation
0925 Tasimelteon Improves Sleep Quality and Behavior in Individuals with Smith-Magenis Syndrome (SMS) in an Open-Label Study
No full text0985 Differences in the Timing of Melatonin Secretion between African American and Caucasian Patients with Major Depressive Disorder
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