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Francesco Pesce,1 Giacomo Matteo Bruno,2 Giorgio Lorenzo Colombo,2 Sergio Di Matteo,3 Anna Rita Maurizi,4 Valentina Mongelli,4 Silvia Mele,5 Lavinia Narici,5 Stefano Bianchi,6 Mario Bonomini,7 Giuseppe Castellano,8 Luca De Nicola,9 Giovanni Gambaro,10 Giuseppe Grandaliano,11 Gaetano La Manna,12 Antonello Pani,13 Andrea Ranghino,14 Loreto Gesualdo15 1Division of Renal Medicine, “Fatebenefratelli Isola Tiberina—Gemelli Isola”, Rome, 00186, Italy; 2Department of Drug Sciences, University of Pavia, Pavia, Italy; 3S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy; 4Cardiovascular, Renal and Metabolism Medical Affairs, AstraZeneca, Milan, Italy; 5Value & Access, AstraZeneca, Milan, Italy; 6Nephrology and Dialysis Unit, Department of Internal Medicine, ASL Toscana Nordovest, Regione Toscana, Livorno, Italy; 7Department of Medicine, Section of Nephrology and Dialysis, G. D’Annunzio University, Chieti, 66013, Italy; 8UOC of Nephrology, Dialysis, and Kidney Transplant, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 9Department of Advanced Medical and Surgical Sciences, Nephrology and Dialysis Unit, University Vanvitelli, Naples, Italy; 10Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy; 11Department of Translational Medicine and Surgery, Università Cattolica Sacro Cuore, Rome, Italy; 12Nephrology Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; 13Department of Nephrology and Dialysis, G. Brotzu Hospital, Cagliari, Italy; 14Nephrology, Dialysis and Kidney Transplant Unit, Ospedali Riuniti Ancona, Ancona, Italy; 15Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (Dimepre-J), University of Bari “aldo Moro”, Bari, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email colombog@unipv.itIntroduction: The underdiagnosis of chronic kidney disease (CKD) remains a significant public health concern. The Early chroNic kiDney disease pOint of caRe Screening (ENDORSE) project aimed to evaluate the clinical and economic implications of a targeted training intervention for general practitioners (GPs) to enhance CKD awareness and early diagnosis.Methods: Data on estimated Glomerular Filtration Rate (eGFR) and Urinary Albumin-Creatinine Ratio (uACR) were collected by 53 Italian GPs from 112,178 patients at baseline and after six months. The intervention involved six months of hybrid training provided by 11 nephrologists, which included formal lectures, instant messaging support, and joint visits for complex cases.Results: The results demonstrated a substantial increase in the use of eGFR (+44.7%) and uACR (+95.2%) tests. This led to a 128.9% rise in the number of individuals screened for CKD using the KDIGO classification, resulting in a 62% increase in CKD diagnoses. The intervention’s impact was particularly notable in high-risk groups, including patients with type 2 diabetes, hypertension, and heart failure.Discussion: A budget impact analysis projected cumulative five-year savings of € 1.7 million for the study cohort. When these findings were extrapolated to the entire Italian CKD population, potential savings were estimated at € 106.6 million, highlighting significant cost savings for the national health service. The clinical simulation assumed that early diagnosed CKD patients would be treated according to current indications for dapagliflozin, which slows disease progression.Conclusion: The ENDORSE model demonstrated that targeted training for GPs can significantly improve early CKD detection, leading to better patient outcomes and considerable economic benefits. This approach shows promise for broader implementation to address the underdiagnosis of CKD on a national and potentially international scale. Keywords: eGFR, uACR, awareness, chronic kidney disease, general practice, economic impact, training intervention, early diagnosis

Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug’s safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11–16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3–15.4%), neutropenia was 7.1% (95% CI, 4.6–10.4%), and anemia was 11.3% (95% CI, 8.0–15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians.

Ralstonia spp. are low-virulent environmental Gram-negative bacteria that can cause serious nosocomial infections in immunocompromised patients. We report the characteristics of a cluster of R. insidiosa bacteremia cases occurring in our oncology day ward in Milan, Italy, between January and March 2022. A case was defined as a cancer patient attending our day ward and whose blood culture (performed because of bacteremia symptoms) led to the isolation of Ralstonia insidiosa. An epidemiological investigation was conducted in order to seek the possible source of infection. Seven adult patients received curative or palliative treatment via infusion through a Port-a-Cath (PAC). All developed symptoms within 24 h of the infusion (three during the infusion itself). Ralstonia insidiosa was isolated in the blood drawn from the PAC in all patients. All of the isolates were susceptible to carbapenems, fluoroquinolones, and piperacillin/tazobactam but resistant to aminoglycosides and cephalosporins. Systemic and/or lock antibiotic therapy led to stable symptom resolution and negative blood cultures in five patients, whereas bacteremia recurred in two patients. An epidemiological investigation suggested that extrinsic contamination of antiseptic solutions was the possible cause of the R. insidiosa infections. Although R. insidiosa is not considered a virulent pathogen, clinicians, microbiologists, and infection control teams should be aware about its potential to cause outbreaks of nosocomial bloodstream infections, especially in immunocompromised patients bearing central venous catheters.

The number of primary total hip arthroplasties (THAs) and revisions is expected to steadily grow in the future. The femoral revision surgery can be technically demanding whether severe bone defects need to be addressed. The femoral revision aims to obtain a proper primary stability of the stem with a more proximal fixation as possible. Several authors previously proposed classification systems to describe the morphology of the bony femoral defect and to drive accordingly the surgeon in the revision procedure. The previous classifications mainly considered cortical and medullary bone at the level of the defect of poor quality by definition. Therefore, the surgical strategies aimed to achieve a distal fixation bypassing the defect or to fill the defect with bone impaction grafting or structured bone grafts up to the replacement of the proximal femur with megaprosthesis. The consensus on a comprehensive and reliable classification system and management algorithm is still lacking. A new classification system should be developed taking into account the bone quality. The rationale of a new classification is that ‘functional’ residual bone stock could be present at the level of the defect. Therefore, it can be used to achieve a primary (mechanical) and secondary (biological) stability of the implants with a femoral fixation more proximal as possible.

The study of aerosols in high mountain regions is essential because particulate matter can play a role in altering the energy balance of high mountain regions, and aerosols can accelerate glacier melting in high mountain areas by darkening the ice surface, reducing its reflectivity (albedo). Studying aerosols in high mountain areas provides insights into long-range transport of pollutants, atmospheric dynamics, and climate change impacts. These regions can serve as valuable observatories for studying atmospheric processes. The main aim of this paper is to define the main sources of aerosols over an entire year of sampling at the Col Margherita Atmospheric Observatory (MRG; 46°22′0.059′′ N, 11°47′30.911′′ E; 2543 m a.s.l.), a high-altitude background site in the eastern Italian Alps. Here, we discuss the potential origins of more than 100 chemical markers (major ions, water-soluble organic compounds, trace elements, and rare earth elements) using different approaches. Some diagnostic ratios were applied, but source apportionment using positive matrix factorization (PMF) was used to define the main inputs of PM10 collected at this high-altitude site, resulting in the identification of four factors: (1) Saharan dust events, (2) long-range marine/anthropogenic influence, (3) biogenic sources, and (4) biomass-burning and anthropogenic emissions. It can be inferred that, despite the distant location of the Col Margherita site, both regional pollution and long-range anthropogenic pollution have discernible effects on this area.

Abstract Objectives This study's primary purpose was to demonstrate the correlation of preoperative right ventricular free‐wall longitudinal strain (RVFWLS) and pre‐/postsurgical variation in strain (delta strain) with the clinical and echocardiographic diagnosis of right ventricular dysfunction. Its secondary purpose was to determine the correlation of RVFWLS and delta strain with length of stay (LOS) in the intensive care unit (ICU), ventilation days, trend of natriuretic peptide test. (NT‐proBNP) and lactate in the first 48 h, incidence of acute renal failure, and 28‐day mortality. Design Prospective observational study. Setting Cardio‐thoracic and Vascular Anaesthesia Department and ICU of the University Hospital Integrated Trust of Verona. Participants Patients scheduled for mitral surgery. Interventions None. Measurements and Main Results All clinical and transoesophageal echocardiographic (TEE) parameters were collected at baseline, before surgery (T1) and at admission in the ICU postsurgery (T2). During the postoperative period, the clinical and echocardiographic diagnoses of right, left, or biventricular dysfunction were evaluated. TEE parameters were evaluated by a cardiologist offline. The patients were divided into two subgroups according to the development of any type of ventricular dysfunction. No statistically significant differences emerged between the two groups. According to a logistic regression model, a T1‐RVFWLS value of −15% appeared to predict biventricular dysfunction (sensitivity: 100%; specificity: 91.3%). No correlation between T1‐ or T2‐RVFWLS and creatinine, hours of ventilation or ICU LOS was found. Conclusions Our study introduces a new parameter that could be used in perioperative evaluations to identify patients at risk of postoperative biventricular dysfunction.

Aim: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up: Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies. Prophylaxis: Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most “high-risk” patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at “high-risk” forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched. Future research: Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation.

Background: A significant loss in bone density and strength occurs during the post-renal-transplant period with higher susceptibility to fracture. The study aims to compare the performance of the Radiofrequency Echographic Multi Spectrometry (REMS) in the bone mineral density assessment with the conventional dual-energy X-ray absorptiometry (DXA) in a cohort of kidney transplant recipients (KTR). Methods: A cohort of 40 patients underwent both DXA and REMS examinations on the lumbar spine and/or proximal femur. The paired t-test was used to compare DXA and REMS measurements; the chi-square test was used to compare the prevalence of osteoporosis/osteopenia. The agreement between the two techniques was assessed through Spearman’s correlation. Results: As expected, most KTR patients were osteopenic or osteoporotic with both REMS and DXA (86.5% and 81% for the femur; 88% and 65% for the lumbar spine p < 0.05). A modest correlation (r = 0.4, p < 0.01) was observed at the lumbar spine between the T-score measured by REMS and DXA. A strong correlation was defined between REMS and DXA in the femoral region (r = 0.7, p < 0.0001). Conclusions: The study demonstrates the exchangeability of the two techniques on the proximal femur in KTR and a higher diagnostic accuracy of REMS at the spine level than DXA.