Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the 4th cause of end-stage renal disease in Western Countries, nevertheless still represents an illness with a significant unmet medical need. In recent years, deregulation in glucose metabolism in ADPKD has been identified. Data suggest that cystic cells shift their energy metabolism from oxidative phosphorylation to aerobic glycolysis. Preclinical experiences show beneficial effects in terms of cystic size reduction, interstitial fibrosis and disease progression, targeting these deregulated metabolic pathways by ketosis induction. A ketogenic diet treatment approach, such as a Modified Atkins Diet (MAD), to ADPKD represents an interesting therapeutic strategy, because of its low cost, tolerability and safety [1]. The Primary Endpoint of this study is the evaluation of the effect of the MAD protocol on the modification of the Total Kidney Volume (TKV), formally qualified, both by FDA and by EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline. Method the initial protocol [2] has been modified in a multicentric study that involves the Divisions of Nephrology of AOU Policlinico di Modena (Modena, Italy) and Policlinico di Sant'Orsola (Bologna, Italy). GREASE II is supported by the Italian Ministry of Health (Ricerca Finalizzata grant no. RF-2021-12374522). During the run-in period, 90 patients will follow a Balanced Normocaloric Diet (BND). In the week preceding the randomization, patients will perform a baseline MRI. Patients will be then randomized to MAD or BND according to a stratified 1:1 ratio. Patients will be followed for 12 months at scheduled clinical and dietetic visits. In the 12ve month, the patients on the MAD arm will be switched to BND and a second MRI will be performed after a month (± 7 days). After the MRI, the patients will be switched again to their original MAD. Patients will be followed for further 12 months at scheduled clinical and dietetic visits. At the 24th month, patients of the MAD arm will be switched once again to BND and after a month (± 7 days) a final visit will be performed (Fig. 1). As co-primary endpoint tolerability and safety will be assessed. Furthermore, as secondary outcomes, the study will evaluate renal function decline, total liver volume (TLV) and the impact of the diets on urinary and serum markers β2MG and MCP-1. Results we expect to obtain a reduction of the TKV in the group of patients treated by the MAD protocol. Safety and tolerability are coprimary endpoints of the study. As secondary exploratory outcomes, the study will evaluate the effect of the diet on the TLV and quality of life (ADPKD-IS and SF-12 questionnaires). This clinical trial will allow us to evaluate the proof of concept of the therapeutic efficacy of MAD in the ADPKD clinical setting. Conclusion GREASE II represents the first multicenter RCT evaluating the reduction of the TKV in ADPKD and renal function decline. The identification of a coordinated reduction of TKV and renal function decline in the patients randomized to the MAD compared to the BND will suggest a protective role of the ketogenic diet against disease progression of ADPKD.
As much as 16-17% European and American patients on renal replacement therapy do not have a conclusive diagnosis of the cause of their renal failure. This may have important implications on the types of morbidity they can develop in case of systemic diseases with extrarenal involvement, or recurrent renal diseases in transplanted patients. A better knowledge of the underlying disease can have important prognostic and therapeutic repercussions. In this study we evaluated the rate of uremic patients who can benefit from a genomic diagnostic approach. Patients liable to a future genomic diagnostic study were selected based on two criteria: (i) age of dialysis entry less or equal to 55 years, and (ii) presence of a non-conclusive diagnosis. Based on the data extracted from the REGDIAL registry, we analyzed 534 patients undergoing renal replacement therapy. We identified 300 patients with age of entry into replacement therapy <55 years (56.2% of the overall study population). Among these, we identified 107 patients with missing or inconclusive diagnosis, which was equal to 20% of the overall population. Of these patients, 32.8% reported a positive family history of kidney disease. This study confirms that a significant proportion of patients on renal replacement therapy do not have an etiological diagnosis and may be subject to a genomic evaluation. With the increasing availability of genomic sequencing technology and the falling of related costs, nephrologists will be increasingly inclined to incorporate clinical genetic testing into their diagnostic armamentarium. There is therefore a need for in-depth, multicenter studies aimed at developing evidence-based guidelines, clear indications and at confirming the usefulness of genetic testing in nephrology.
The mechanisms governing the epidemiology dynamics and success determinants of a specific healthcare-associated methicillin-resistant S. aureus (HA-MRSA) clone in hospital settings are still unclear. Important epidemiological changes have occurred in Europe since 2000 that have been related to the appearance of the ST22-IV clone. Between 2006 and 2010, we observed the establishment of the ST22-IV clone displacing the predominant Italian clone, ST228-I, in a large Italian university hospital. To investigate the factors associated with a successful spread of epidemic MRSA clones we studied the biofilm production, the competitive behavior in co-culture, the capacity of invasion of the A549 cells, and the susceptibility to infection in a murine model of acute pneumonia of the two major HA-MRSA clones, ST22-IV and ST228-I. We showed that persistence of ST22-IV is associated with its increased biofilm production and capacity to inhibit the growth of ST228-I in co-culture. Compared to ST228-I, ST22-IV had a significantly higher capacity to invade the A549 cells and a higher virulence in a murine model of acute lung infection causing severe inflammation and determining death in all the mice within 60 hours. On the contrary, ST228-I was associated with mice survival and clearance of the infection. ST22-IV, compared with ST228-I, caused a higher number of persistent, long lasting bacteremia. These data suggest that ST22-IV could have exploited its capacity to i) increase its biofilm production over time, ii) maintain its growth kinetics in the presence of a competitor and iii) be particularly invasive and virulent both in vitro and in vivo, to replace other well-established MRSA clones, becoming the predominant European clone.
Background. Chronic dialysis is a relevant risk factor for mortality and morbidity after cardiac surgery and cardiopulmonary bypass. The aim of this study was to evaluate the short- and long-term follow-up of patients in dialysis undergoing cardiac surgery. Methods. We retrospectively reviewed 24 consecutive chronic hemodialysis adult patients (14 males, 10 females, mean age 63 ± 12 years) who, over a 10-year period, underwent operative cardiac procedures in our Institution. Prior to surgery the mean duration of dialysis was 55 ± 18 months (minimum 3 months). Surgery included isolated coronary artery bypass grafting in 18 patients, aortic valve replacement in 3, mitral valve replacement in 2, and double valve replacement (mitral and aortic) in 1. Sixteen operations were elective whereas 8 (33%) were performed in an emergency setting. Results. Seven operative deaths occurred with an overall in-hospital mortality of 29%. Among the 16 patients in whom surgery was elective, only 2 died. Five of the 8 patients submitted to emergency procedures died. Hence, the operative mortality in this subgroup of patients was 62% (p < 0.005). A low cardiac output and multiorgan failure due to pulmonary infection were the most important causes of death. However 75% of patients experienced some major postoperative complications. All survivors were followed up for 6 to 108 months (mean 33.7 ± 29.5 months). The overall functional status was significantly improved. Survival at 1, 2 and 5 years was 68, 63 and 45% respectively in coronary patients and 65, 58 and 42% in the overall study population. Conclusions. In dialysis-dependent patients major cardiac procedures can be carried out with an acceptable risk only in elective conditions even if the mortality is 4-5-fold higher than in the normal population and the life expectancy is similar to that of patients in chronic dialysis but without cardiac disease. (Ital Heart J Suppl 2002; 3 (7): 746-752)
The prevalence of the three main eating disorders (EDs) anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) is increasing, and a growing number of patients with EDs is seeking professional help. Thus, there is a need for additional treatment strategies in EDs. The aim of this review was to summarize the literature on the benefits and risks of music as well as the evidence for its therapeutic application in people with EDs.Following the PRISMA guidelines, we performed a systematic literature review on scientific studies on the effect of music in people with or at risk for EDs using PubMed and the Web of Science database. The search terms used were: "music", "music therapy", "eating disorders", "anorexia nervosa", "bulimia nervosa" and "binge eating disorder".16 out of 119 identified and screened articles qualified as scientific studies involving a total of 3,792 participants. They reported on the use of music or music therapy in individuals with or at risk of AN and BN, but not BED. In inpatients with AN, listening to classical music was beneficial to food consumption. Singing in a group reduced post-prandial anxiety in AN inpatients and outpatients. Vodcasts which also included positive visual or autobiographical stimuli helped BN patients with anxiety and body image perception. Songwriting and sessions with a Body Monochord helped with the processing of therapeutically relevant topics in AN. Watching music videos, however, reinforced body dissatisfaction, drive for thinness, bodyweight concerns, preoccupation with physical appearance in pre-teenage and teenage girls, and drive for muscularity in adolescent boys.These findings suggest that the therapeutic application of music may be beneficial in patients with AN and BN. However, the availability of studies with a rigorous randomized controlled trial (RCT) design is scarce.
Table S2. â Analysis of ATP- and PAF-evoked calcium as well as PC1 and TRPP2 expression in ADPKD patientsâ . In this table are inserted the values of PC1 and TRPP2 expression, data of ATP- and PAF-evoked calcium measured in ADPKD and control subjects as well as in wild type and PKD2 silenced Jurkat cells. The type of PKD mutation (when known) is also shown. (XLSX 27 kb)
Digital pathology and artificial intelligence offer new opportunities for automatic histologic scoring. We applied a deep learning approach to IgA nephropathy biopsy images to develop an automatic histologic prognostic score, assessed against ground truth (kidney failure) among patients with IgA nephropathy who were treated over 39 years. We assessed noninferiority in comparison with the histologic component of currently validated predictive tools. We correlated additional histologic features with our deep learning predictive score to identify potential additional predictive features.Training for deep learning was performed with randomly selected, digitalized, cortical Periodic acid-Schiff-stained sections images (363 kidney biopsy specimens) to develop our deep learning predictive score. We estimated noninferiority using the area under the receiver operating characteristic curve (AUC) in a randomly selected group (95 biopsy specimens) against the gold standard Oxford classification (MEST-C) scores used by the International IgA Nephropathy Prediction Tool and the clinical decision supporting system for estimating the risk of kidney failure in IgA nephropathy. We assessed additional potential predictive histologic features against a subset (20 kidney biopsy specimens) with the strongest and weakest deep learning predictive scores.We enrolled 442 patients; the 10-year kidney survival was 78%, and the study median follow-up was 6.7 years. Manual MEST-C showed no prognostic relationship for the endocapillary parameter only. The deep learning predictive score was not inferior to MEST-C applied using the International IgA Nephropathy Prediction Tool and the clinical decision supporting system (AUC of 0.84 versus 0.77 and 0.74, respectively) and confirmed a good correlation with the tubolointerstitial score (r=0.41, P<0.01). We observed no correlations between the deep learning prognostic score and the mesangial, endocapillary, segmental sclerosis, and crescent parameters. Additional potential predictive histopathologic features incorporated by the deep learning predictive score included (1) inflammation within areas of interstitial fibrosis and tubular atrophy and (2) hyaline casts.The deep learning approach was noninferior to manual histopathologic reporting and considered prognostic features not currently included in MEST-C assessment.This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_26_CJN01760222.mp3.
