Italian Multicenter Study Research Articles

Body weight and body surface area of adult patients with selected cancers: An Italian multicenter study.

Although body weight (BW) and body surface area (BSA) are utilized to establish the appropriate dosage of anticancer drugs, their distribution in cancer patients is poorly studied, making it challenging to predict the amount of drug use and related costs of BW or BAS-dosed regimens. This study investigates the distribution of BW and BSA in adults with selected cancers who initiated systemic anticancer treatment in the eastern Emilia-Romagna region hospitals between 2011 and 2021. BW and BSA were collected at the first cycle of each new treatment line, with multiple measurements for patients receiving various treatments or treating for other primary malignancies. Results were grouped by sex, tumor site and treatment setting, and the normal distribution hypothesis was tested for each group. Both linear regression model and quantile regression at the 50th, 25th and 75th percentiles were run to explore the factors influencing BSA. The analysis included 20,634 treatment lines and the corresponding BW and BSA measures from a sample of 13,036 patients. The average BW was 68.05kg (64.20kg for females and 75.07kg for males) and the average BSA was 1.76m2 (1.66m2 for females and 1.87m2 for males). In women, the highest BW was in breast and colon groups, while in men, it was associated with prostate and rectum cancers. The model indicated significant association between BSA, age, sex and tumor localization. Notably, stomach and lung cancers were linked to lower BSA for both sexes (for females -0.081 and -0.041m2 respectively compared to those with breast cancer). Advanced settings were related to lower BSA than neoadjuvant treatment, especially for stomach cancer patients, who experienced a weight loss of 3 to 6kg as therapy progressed. The regression models for predicting BSA can assist regulatory bodies in determining reimbursement for new chemotherapy drugs and help hospitals forecast drug utilization and expenditure more accurately.

Prevalence and determinants of no mobile phone phobia among university students: an Italian multicenter study

ObjectiveAs the Internet has undergone a significant increase, the smartphone has become the primary electronic device used for accessing it. However, several adverse effects on health and also psychological disorders, such as the fear of not being able to use a mobile phone and/or its services, called nomophobia, may be related to their use. This multicenter study was aimed at evaluating the prevalence, the correlates and the predictors of nomophobia in a large sample of university students recruited throughout the Italian territory.MethodsStudents attending 12 Italian universities were asked to complete a web-based questionnaire investigating their sociodemographic and behavioral characteristics and including the Nomophobia-Questionnaire, items from the Generalized Anxiety Disorder and the Patient Health Questionnaire.Resultsout of 1303 respondents (mean age 24.1 ± 4.4, 69.5% females), 454 (34.8%) showed a medium/severe profile of nomophobia which seems to be related with attention to diet (PR 0.831, 95%CI 0.715–0.966, p = 0.016), physical activity levels (PR 0.799, 95%CI 0.682–0.934, p = 0.005), and alcohol consumption (PR 1.290, 95%CI 1.010–1.647, p = 0.042). Furthermore, nomophobia was slightly related with a predisposition to anxiety (rho = 0.2312, p < 0.001) and depression (rho = 0.0699, p = 0.0116).ConclusionsThe results indicated that in the sample examined nomophobia profile is associated with unhealthy behaviors, and then this finding suggested that awareness and control of health risks related to the use of mobile phones should be increased in the population examined.

Controlling nutritional status score and geriatric nutritional risk index as a predictor of mortality and hospitalization risk in hospitalized older adults

BackgroundThe COntrolling NUTritional Status (CONUT) score and the Global Nutrition Risk Index (GNRI) are screening tools for assessing the risk of malnutrition based on widely available biochemical parameters. The primary objective of this study was to investigate the predictive value of CONUT and GNRI score on 36 months mortality and hospitalization risk in hospitalized older patients. MethodsData of 382 patients (196 women, mean age 80.9±6.8 years) were retrieved from the multicenter Italian Study conducted by the Gruppo Lavoro Italiano Sarcopenia–Trattamento e Nutrizione (GLISTEN) in 12 Acute Care Wards. Sarcopenia was defined as presence of low handgrip strength plus low skeletal mass index (EWGSOP2 criteria). CONUT score was calculated based on serum albumin, total cholesterol and total lymphocyte count, whilst the GNRI was calculated using serum albumin and present body weight/ideal body weight ratio. ResultsDuring the 36-month follow-up, 120 out of 382 participants died (31.4%). From the results of the survival analysis, and after adjustment for potential confounders, participants with CONUT-derived moderate to high risk of malnutrition had shorter survival (HR = 2.67, 95%CI 1.34–5.33 and HR = 3.98, 95% CI: 1.77–8.97, respectively), as well as shorter survival free of urgent hospitalization (HR = 1.91; 95% CI: 1.03–3.55 and HR = 1.98; 95% CI: 1.14–3.42, respectively). Conversely, only GNRI indicative of high risk of malnutrition was an independent predictor of mortality 1.96 (95% CI: 1.06–3.62), but not of hospitalization. ConclusionThe CONUT score seems a valid tool to predict long-term mortality and hospitalization risk. Conversely, the GNRI is associated with long-term mortality, but not with hospital readmissions.

False-Positive Diagnosis of Congenital Heart Defects at First-Trimester Ultrasound: An Italian Multicentric Study.

Objective. Our objective was to assess the proportion of false-positive CHD cases at the first-trimester evaluation of the fetal heart, performed by experienced operators. Methods. This multicenter retrospective study included of pregnant women with suspicion of CHDs during first-trimester screening for aneuploidies. In all cases, the fetal heart assessments were performed by obstetricians with extensive experience in first-trimester scanning, following an extended protocol proposed by SIEOG national guidelines, which included an axial view of the fetal abdomen and chest to assess visceral situs and evaluation of the four-chamber view (4CV) and three-vessel trachea view (3VTV) with color Doppler. In all suspected cases, fetal echocardiography was offered within 16 and/or at 19-22 weeks' gestation. Results. From a population of 4300 fetuses, 46 CHDs were suspected. Twenty-four cases were excluded from this analysis because the parents opted for early termination of the pregnancies due to associated structural and/or genetic anomalies. For the remaining 22, echocardiography was performed by 16 weeks in 14 cases (64%) and after 16 weeks in 8 cases. In 19 cases (86.4%), a fetal cardiologist confirmed the presence of a CHD. In three cases (13%), the cardiac anatomy was found to be normal at the fetal echocardiography and postnatally. Conclusions. This study shows that the proportion of false-positive cases at the first-trimester ultrasound examination of the fetal heart, performed by experienced operators, may carry a higher risk of false-positive diagnosis than expected. Therefore, this issue must be discussed in instances where a CHD is suspected at the first-trimester screening.

Motivations for Enrolment and Dropout of First-Year Undergraduate Nursing Students: A Pilot Multimethod Study.

Higher education institutions must improve the attractiveness and retention of the nursing profession to address the widespread shortage. This pilot multimethod study aimed to preliminarily understand the relationship between motivations for enrolment and dropout among first-year undergraduate nursing students. A two-step approach was conducted among first-year nursing students from five Italian universities involving: (a) a baseline quantitative online survey collecting their characteristics and motivations for enrolment; (b) a follow-up semi-structured interview qualitative data collection among students who dropped out. Descriptive and inferential statistics were used to describe the motivations for enrolment and differences between universities. Dropout motivations emerged from inductive content analysis, with data categorisation according to Urwin's framework. A total of 759 students completed the online survey. Primary motivations for enrolment included the desire to be useful (88.8%), help suffering people (84.3%), and find employment (74.2%); 22.3% cited unsuccessful admission to another university as motivation for enrolment. Of the 141 students who discontinued, 31 were interviewed (22%). Eleven categories and three themes were identified. More than half of the participants dropped out due to interest in other courses and lack of aptitude, while a smaller number cited personal circumstances. Other motivations for dropout were related to negative learning environments or feelings and difficulties related to course characteristics. This study provides an initial insight into these complex phenomena that will be instrumental in understanding data from an Italian multicenter cohort study. The findings can inform recommendations and strategies to strengthen the future nursing workforce.

Prognostic Impact of IMDC Category Shift From Baseline to Nivolumab Initiation in Metastatic Renal Cell Carcinoma: A Sub-Analysis of the MEET-URO 15 Study

IntroductionThe International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score is the most important prognostic score to stratify patients with metastatic renal cell carcinoma (mRCC), helping to guide treatment choice in first line. We hypothesized that IMDC change may also exert a prognostic role in subsequent lines of mRCC therapy. MethodsMeet-URO 15 is a multicenter Italian study of patients with mRCC receiving nivolumab as a second or subsequent line of therapy. This posthoc analysis aimed to evaluate the overall survival (OS) and progression-free survival (PFS) from nivolumab start as primary endpoints, overall response rate (ORR) and disease-control rate (DCR) as secondary endpoints, according to the change in the IMDC category from the first-line setting (baseline) to nivolumab start. Patients with available prognostic IMDC category information at baseline and before nivolumab were included. Results492 patients were included in the analysis. At baseline, 165 (33.5%), 287 (58.3%), and 40 patients (8.2%) had favorable, intermediate, and poor IMDC categories, respectively. Before nivolumab, 364 patients (73.9%) remained in the same prognostic category as at baseline, 27 (5.5%) improved, and 101 (20.5%) deteriorated. Significantly longer mPFS (P = .01) and mOS (P < .01) were reached by patients with a stable favorable group compared to those worsening to intermediate/poor. A longer mOS was also achieved from intermediate/poor patients who improved their IMDC category before nivolumab compared to those remaining stable/worsening (P < .01 and P = .04, respectively). Maintaining IMDC category stability from baseline to nivolumab determined a more consistent DCR in favorable patients (P = .03). Overall, patients who improved their IMDC risk score reached better survival outcomes than those who remained stable/deteriorated. ConclusionsIn our sub-analysis, the shift in the IMDC risk category appears to be a helpful prognostic tool for assessing the outcomes of patients with mRCC treated with ≥2nd line nivolumab.

Pomalidomide, Bortezomib and Dexamethasone in Multiple Myeloma Patients Double Refractory to Lenalidomide and Anti-CD38 Monoclonal Antibodies: A Multicentric Italian Retrospective Study

Pomalidomide, Bortezomib and Dexamethasone in Multiple Myeloma Patients Double Refractory to Lenalidomide and Anti-CD38 Monoclonal Antibodies: A Multicentric Italian Retrospective Study

Qol-Blina Protocol: Preliminary Data of a Paediatric Italian Multicentric Study

Qol-Blina Protocol: Preliminary Data of a Paediatric Italian Multicentric Study

Bortezomib for rituximab-refractory immune-mediated thrombotic thrombocytopenic purpura in the caplacizumab era: an Italian multicenter study

BackgroundImmune-mediated thrombotic thrombocytopenic purpura (iTTP) patients are not responsive to standard rituximab in approximately 10-15% of cases, and oral immunosuppressants showed controversial results with significant toxicity. Targeting plasma cells with bortezomib appears promising, but available evidence is scarce and stems only from isolated reports in the pre-caplacizumab era. ObjectivesTo evaluate the safety and efficacy of bortezomib in rituximab-refractory iTTP patients. MethodsWe conducted a retrospective observational multicenter study among 13 Italian iTTP-treating centers, collecting data from May 2017 to May 2023 (caplacizumab licensed in Italy in January 2020). ResultsBortezomib was effective in 10/17 patients (59%). Eleven were treated in the acute phase (9/11 responders, 82%, allowing discontinuation of caplacizumab in 5/6 treated patients), and 7 during clinical remission (2/7 responders, 28%). Responses occurred at a median time of 30 days, but 3 patients responded after 4 months. The median duration of response was 22 months (IQR 10-38), still ongoing in 6 patients at the time of data cut-off. Responders had fewer previous acute iTTP episodes than non-responders [median (IQR) 1 (1-2) vs 5.5 (2-7), p=0.03]. Eight subjects (47%) reported toxicities, mostly in those treated with ≥2 cycles. ConclusionDurable responses to bortezomib were registered in about 60% of multi-refractory iTTP patients, with mild-to-moderate toxicities. The occurrence of late responses (i.e., after 30 days) suggests a “watchful waiting” approach after bortezomib treatment.

Maternal and perinatal outcomes in pregnant women with heart disease: an Italian multicentre observational study

Maternal and perinatal outcomes in pregnant women with heart disease: an Italian multicentre observational study

The newborn at risk of hypoxic-ischemic encephalopathy: a large Italian multicentre retrospective study on antepartum and peripartum risk factors

The newborn at risk of hypoxic-ischemic encephalopathy: a large Italian multicentre retrospective study on antepartum and peripartum risk factors

Epidemiological characteristics of non-polio enteroviruses in respiratory infections: an Italian multicentre retrospective study, 2022-2023.

Epidemiological characteristics of non-polio enteroviruses in respiratory infections: an Italian multicentre retrospective study, 2022-2023.

Italian validation of the IBD-disk tool for the assessment of disability in inflammatory bowel diseases: A cross-sectional multicenter study

IntroductionIBD-Disk is a simple, easy-to-use, and self-administered analogue visual tool for assessing disability in patients with Inflammatory Bowel Disease (IBD). However, it has not yet been validated in Italian. This study aims to validate IBD-Disk in an Italian cross-sectional multicentre study. MethodsThis study was conducted in eight IBD centres from February 2023 to October 2023. After forward-backwards translation of IBD-Disk into Italian, patients consecutively completed IBD-Disk (at baseline and after 7 days), IBD-Disability Index (IBD-DI) and IBDQ-32 for quality of life. ResultsWe enrolled 767 patients (377, 49,2% CD; 390, 50,8% UC) who completed the IBD-Disk [median score of 30 (IQR=11–52)]. Internal consistency was excellent, with Cronbach's α of 0.92 (95%CI=0.92–0.92). To evaluate the validity, the IBD-Disk was compared with the IBD-DI and IBDQ-32, revealing a significant positive correlation of 0.70 (95% CI=0.66–0.73; p<0.001) and 0.83 (r=0.83, 95% CI=0.80–0.85; p<0.001), respectively. The intraclass correlation coefficient (ICC) was 0.84 (95% CI=0.82–0.86) for test-retest. Female gender, clinically active IBD and the presence of extraintestinal manifestations led to higher IBD-Disk scores. ConclusionThis study validated the IBD-Disk in a large cohort of Italian IBD patients, demonstrating that it is a valid, reliable and responsive tool for quantifying IBD-related disability. This validation facilitates its integration into the daily clinical management of IBD patients.

Feasibility of IAPWG protocol in performing high-definition three-dimensional anorectal manometry: A prospective, multicentric italian study.

The International Anorectal Physiology Working Group (IAPWG) suggests a standardized protocol to perform high-resolution anorectal manometry. The applicability and possible limitations of the IAPWG protocol in performing three-dimensional high-definition anorectal manometry (3D-ARM) have still to be extensively evaluated. The IAPWG protocol was applied in performing 3D-ARM. Anorectal manometry (ARM) and a balloon expulsion test (BET) were performed according to IAPGW protocol in 290 patients. A total of 84 males and 206 females (mean age 57.1 ± 15.7years) were enrolled in six Italian centers. The reasons for which the patients were sent to perform 3D-ARM were: constipation (53.1%), fecal incontinence (26.9%), anal pain (3.1%), postsurgical (3.8%) and presurgical evaluation (4.8%), prolapse (3.4%), anal fissure (2.8%), and other (2.1%). Due to organic and functional conditions (low rectal anterior resections, rectal prolapses, and J-pouch after colectomy), we were unable to perform a complete 3D-ARM on six patients. Overall, a complete 3D-ARM and BET following IAPWG protocol was carried out in 284 patients (97.9%). The following were recorded: rest pressure (81.9 ± 32.0mmHg) and length of the anal sphincter (37.0 ± 6.2cm), maximum anal squeeze pressure (201.6 ± 81.3mmHg), squeeze duration (22.0 ± 8.8s), maximum rectal (48.7 ± 41.0mmHg) and minimum anal pressure (73.3 ± 36.5mmHg) during push, presence/absence of a dyssynergic pattern, cough reflex and rectal sensations (first constant sensation 48.4 ± 29.5mL, desire to defecate 83.7 ± 52.1mL, and maximum tolerated volume 149.5 ± 72.6mL), and presence/absence of rectoanal inhibitory reflex. Mean 3D-ARM registration time was 14 min 7 s ± 3 min 12 s. This is the first multicentric study that evaluates the applicability of the IAPWG protocol in 3D-ARM performed in different manometric laboratories (both gastroenterological and surgical). The IAPWG protocol was easy to perform and was not time consuming. A diagnosis according to the London Classification was easily obtained in most patients in which 3D-ARM was carried out. No clear limitations to the applicability of the IAPWG protocol were detected.

Pulmonary Progressive Fibrosis in Rheumatoid Arthritis and Primary Sjogren Syndrome: Similarities and Differences.

Background: Progressive pulmonary fibrosis (PPF) has been associated with a worse prognosis, even when interstitial lung disease (ILD) is related to rheumatic diseases. Since many differences are detectable among rheumatic diseases in prevalence and features of ILD, we aimed to investigate features of PPF in different rheumatic diseases, namely rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS). Methods: In an Italian multicentre cross-sectional study, consecutive pSS or RA patients with a diagnosis of ILD from at least two years were enrolled. For each patient, demographic, clinical, and serological data, other than chest high-resolution computed tomography and lung function tests, were recorded at the enrolment and after 2 years. Results: Among 232 patients, namely 156 RA-ILD and 76 pSS-ILD, a PPF was recorded in 38.8% of cases, without differences between the two diseases. Analysing patients with a PPF, usual interstitial pneumonia was significantly more frequent in RA than pSS (71.4% and 44.4%, respectively; p = 0.019), while ILD preceded the diagnosis of the rheumatic disease in 29.1% of RA and 89.5% of pSS (p < 0.001). Finally, RA patients were significantly younger than pSS at the diagnosis of the rheumatic disease (p < 0.001). Conclusions: In conclusion, although there is a similar prevalence of PPF in RA-ILD and pSS-ILD, we demonstrated for the first time that the two conditions differ in terms of radiological patterns and demographic and clinical features, suggesting that specific factors related to such diseases might influence the lung involvement over time. Prospective studies could investigate if these specificities could induce different responses to the treatment.

Effectiveness of tildrakizumab 200 mg: an Italian multicenter study

Introduction: Psoriasis is a chronic immune-mediated disease that can be challenging to treat, especially in patients with severe disease or high body weight. Tildrakizumab is a monoclonal antibody which inhibits IL-23, approved for moderate-to-severe psoriasis with a standard 100 mg dose. A 200 mg dose may provide greater efficacy for patients over 90 kg or with high disease burden. Methods: This multicenter, prospective study evaluated the effectiveness and safety of tildrakizumab 200 mg in patients with moderate-to-severe psoriasis, focusing on those with specific challenges: body weight over 90 kg, baseline PASI ≥20, and difficult-to-treat areas. The study also compared bio-naive versus bio-experienced and male versus female patients. Adults received tildrakizumab 200 mg subcutaneously at weeks 0 and 4, then every 12 weeks. Results: Clinical improvements were assessed using PASI, DLQI, genital PASI, and NAPSI scores. After 24 weeks, the mean PASI score dropped from 14.6 to 0.4, with PASI 90 and PASI 100 scores exceeding 80% (100.0% and 80.3%, respectively). DLQI scores improved from 14.2 to 1.8, and significant improvements were seen in genital PASI and NAPSI scores. No significant adverse events occurred. Conclusions: Tildrakizumab 200 has been shown to be an effective therapeutic option, particularly for patients with high body weight, significant disease burden, and involvement of sensitive areas with no new safety signals.

Prognostic impact of switching to the 2021 chronic kidney disease epidemiology collaboration creatinine-based equation in Caucasian patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular events (RIACE) Italian Multicenter Study

BackgroundA Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes.MethodsThe Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006–2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%).ResultsWith the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min− 1·1.73 m− 2. The median difference was 4.10 ml·min− 1·1.73 m− 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations.ConclusionChanging from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min− 1·1.73 m− 2, but virtually no impact on mortality prediction.Trial registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Optimal MMSE and MoCA cutoffs for cognitive diagnoses in Parkinson's disease: A data-driven decision tree model

BackgroundDetecting cognitive impairment in Parkinson's disease (PD) is challenging due to diverse manifestations and outdated diagnostic criteria. Cognitive screening tools, as Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), are adopted worldwide, but despite several cutoffs has been proposed for PD, no consensus has been reached, hindered by limited sample sizes, lack of validation, and inconsistent age- and education-adjustments. ObjectivesDetermine the optimal MMSE and MoCA cutoffs in a large PD cohort, spanning from normal cognition (PD-NC), mild cognitive impairment (PD-MCI) to dementia (PDD), and develop a decision tree model to assist physicians in cognitive workups. MethodsOur retrospective Italian multicenter study involves 1780 PD, cognitively diagnosed with a level-II assessment: PD-NC(n = 700), PD-MCI(n = 706), and PDD(n = 374). Optimal cutoffs (for raw scores) were determined through ROC analysis. Then, a machine learning approach—decision trees—was adopted to validate and analyze the possible inclusion of other relevant clinical features. ResultsThe decision tree model selected as primary feature a MMSE cutoff ≤24 to predict dementia, and a score ≤ 27 for PD-MCI. To enhance PD-MCIvs.PD-NC accuracy, it also recommends including a MoCA score ≤ 22 for PD-MCI, and > 22 for PD-NC. Age and education were not selected as relevant features for the cognitive workup. Both MoCA and MMSE cutoffs exhibited high sensitivity and specificity in detecting PD cognitive statues. ConclusionsFor the first time, a clinical decision tree model based on robust MMSE and MoCA cutoffs has been developed, allowing to diagnose PD-MCI and/or PDD with a high accuracy and short administration time.

Changes in 24-hour blood pressure profile after 12 weeks of dapagliflozin treatment in patients with diabetic kidney disease: an Italian multicenter prospective study.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower ambulatory blood pressure (ABP) in patients with type 2 diabetes mellitus; whether the same holds true in diabetic kidney disease (DKD) is unknown. This information is critical to the knowledge of mechanisms of nephroprotection and safety of this therapy. This multicenter prospective study evaluates the changes in ABP after 12weeks of dapagliflozin 10mg/day in a cohort of patients with type 2 DKD and glomerular filtration rate (GFR) >25mL/min/1.73 m2. Primary endpoint was the change of nighttime systolic blood pressure (SBP). Changes of daytime SBP, prevalence of normal dipping (day/night SBP ratio <0.9) and changes in ABP patterns, that is, sustained uncontrolled hypertension (SUCH), white coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and controlled hypertension (CH) were secondary endpoints. Eighty-three of 96 patients completed the study [age 68.7±8.9 years, 73.5% males, GFR 49±17mL/min/1.73 m2, median albuminuria: 0.18 (interquartile range 0.10-0.38) g/24h]. After 12weeks of dapagliflozin, nighttime SBP declined by -3.0mmHg (95% confidence interval -5.2/-0.8mmHg; P=.010) with an improvement of nighttime SBP goal (<110mmHg) from 18.0% to 27.0% (P<.001). Similarly, the prevalence of normal dipping increased (from 31.3% to 50.6%, P=.005). A decrease in daytime (-2.4mmHg; P=.046) and office (-7.9mmHg; P=.009) SBP was also found. The decline of ambulatory and office SBP was associated with increased prevalence of CH (from 6.0% to 18.0%) and significant improvement of SUCH, WUCH and MUCH (P=.009). Albuminuria decreased (P<.001), whereas eGFR did not change (P=.297). Urinary tract infection (4.2%) and acute kidney injury (3.6%) were the main causes of drop-out. Only one patient showed a drop of nighttime SBP below 90mmHg. Dapagliflozin is associated with improvement in circadian blood pressure rhythm with no major safety signal related to excessive blood pressure decrease.

Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients.

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings.