A real-life study of daratumumab combinations in newly diagnosed patients with light chain (AL) amyloidosis.

Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6 months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, p 0.955) likewise the rate of cardiac (33% vs. 30%, p 0.340) and renal (40% vs. 16%, p 0.908) responses. Daratumumab-based regimens demonstrated to be safe and effective in treatment-naïve AL amyloidosis even in advanced stage disease.

Lenalidomide-based triplet regimens in first relapsed multiple myeloma patients: real-world evidence from a propensity score matched analysis.

Lenalidomide and dexamethasone (Rd)-based triplets, in particular carfilzomib-Rd (KRd) and daratumumab-Rd (DaraRd), represent a standard of care in lenalidomide-sensitive multiple myeloma (MM) patients in first relapse. Meta-analysis of randomized clinical trials (RCT), suggested better outcome with DaraRd. Trying to address this issue in clinical practice, we collected data of 430 consecutive MM patients addressed to Rd-based triplets in first relapse between January 2017 and March 2021. Overall, the most common used regimen was DaraRd, chosen in almost half of the cases (54.4%), followed by KRd (34.6%). Different triplets were used much less commonly. In an attempt to limit the imbalance of a retrospective analysis, we conducted a propensity score matching (PSM) comparison between DaraRd and KRd. After PSM, efficacy of DaraRd versus KRd was similar in terms of overall-response rate (ORR) (OR: 0.9, P=0.685) as well as of very good partial response (VGPR) or better (OR: 0.9, P=0.582). The median progression-free survival (PFS) was significantly longer for DaraRd (29.8 vs. 22.5 months; P=0.028). DaraRd was tolerated better, registering a lower rate of grade 3-4 non-hematological toxicity (OR: 0.4, P<0.001). With the limitations of any retrospective analysis, our real-life PSM comparison between DaraRd and KRd, in first-relapse MM patients, showed better tolerability and prolonged PFS of DaraRd, although with some gaps of performance, in particular of DaraRd, with respect to RCT. Carfilzomib-containing regimens, like KRd, still remain a valid second-line option in the emerging scenario of first-line daratumumab-based therapy.

National Early Warning Score 2 (NEWS2) better predicts critical Coronavirus Disease 2019 (COVID-19) illness than COVID-GRAM, a multi-centre study.

PURPOSE: Clinical scores to rapidly assess the severity illness of Coronavirus Disease 2019 (COVID-19) could be considered of help for clinicians. Recently, a specific score (named COVID-GRAM) for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, based on a nationwide Chinese cohort, has been proposed. We routinely applied the National Early Warning Score 2 (NEWS2) to predict critical COVID-19. Aim of this study is to compare NEWS2 and COVID-GRAM score. METHODS: We retrospectively analysed data of 121 COVID-19 patients admitted in two Clinics of Infectious Diseases in the Umbria region, Italy. The primary outcome was critical COVID-19 illness defined as admission to the intensive care unit, invasive ventilation, or death. Accuracy of the scores was evaluated with the area under the receiver-operating characteristic curve (AUROC). Differences between scores were confirmed used Hanley-McNeil test. RESULTS: The NEWS2 AUROC curve measured 0.87 (standard error, SE 0.03; 95% CI 0.80-0.93; p < 0.0001). The COVID-GRAM score AUROC curve measured 0.77 (SE 0.04; 95% CI 0.68-0.85; p < 0.0001). Hanley-McNeil test showed that NEWS2 better predicted severe COVID-19 (Z = 2.03). CONCLUSIONS: The NEWS2 showed superior accuracy to COVID-GRAM score for prediction of critical COVID-19 illness.

When Does the Cytokine Storm Begin in COVID-19 Patients? A Quick Score to Recognize It.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that is responsible for coronavirus disease 2019 (COVID-19), which has rapidly spread across the world, becoming a pandemic. The "cytokine storm" (CS) in COVID-19 leads to the worst stage of illness, and its timely control through immunomodulators, corticosteroids, and cytokine antagonists may be the key to reducing mortality. After reviewing published studies, we proposed a Cytokine Storm Score (CSs) to identify patients who were in this hyperinflammation state, and at risk of progression and poorer outcomes. We retrospectively analyzed 31 patients admitted to Infectious Disease Department in "St. Maria" Hospital in Terni with confirmed SARS-CoV-2 infections, and analyzed the "CS score" (CSs) and the severity of COVID-19. Then we conducted a prospective study of COVID-19 patients admitted after the definition of the CSscore. This is the first study that proposes and applies a new score to quickly identify COVID-19 patients who are in a hyperinflammation stage, to rapidly treat them in order to reduce the risk of intubation. CSs can accurately identify COVID-19 patients in the early stages of a CS, to conduct timely, safe, and effect administration of immunomodulators, corticosteroids, and cytokine antagonists, to prevent progression and reduce mortality.

[A cause of acute renal dysfunction: a giant bladder diverticulum].

We describe the case of a previously 77-year-old man who accessed in our Nephrology Unit for acute kidney injury (AKI) on chronic kidney disease (CKD), gastric discomfort and vague urinary symptoms with apparently preserved diuresis and suspected "ascites". Physical examination confirmed the presence of abdominal effusion, even though ultrasound abdominal examination revealed the presence of a giant diverticular urinary bladder with bilateral hydronephrosis. We discuss the diagnostic and therapeutic approach of these rare complications by briefly reviewing the technical aspects and the possible consequences.

Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial.

BACKGROUND: Urinary tract infection (UTI) is a prevalent condition in women during their lifetime with a high rate of recurrence within 3-6 mo. OBJECTIVES: Our aim was to investigate the efficacy and tolerability of the intravesical administration of combined hyaluronic acid (HA) and chondroitin sulphate (CS) in female patients with a history of recurrent UTI. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective, randomised, double-blind, placebo-controlled study comparing the intravesical instillation of HA-CS with placebo in women with recurrent UTI. INTERVENTION: Participants were randomised to receive 50 ml of sterile sodium HA 1.6% and CS 2.0% solution (IALURIL(®)) weekly for 4 wk and then monthly for 5 mo. MEASUREMENTS: The primary end point of the study was defined as the mean number of UTI per patient per year. Participants were evaluated addressing UTI status/urinary symptoms and with a general health-related quality-of-life (QoL) questionnaire at baseline and after 3, 6, 9, and 12 mo. RESULTS AND LIMITATIONS: In the intention-to-treat analysis, 57 women were randomly allocated to HA-CS (n=28) or placebo (n=29). The UTI rate per patient per year at the end of the study (12 mo) (mean±SD: -86.6%±47.6 vs -9.6%±24.6; mean difference: 77%; 95% confidence interval, 72.3-80.8; p=0.0002) and the mean time to UTI recurrence (52.7±33.4 vs 185.2±78.7 d; p<0.001) were significantly reduced after treatment with HA-CS compared with placebo. Overall urinary symptoms and QoL measured by questionnaires significantly improved compared with placebo (Pelvic Pain and Urgency/Frequency questionnaire symptom score: 14.53±4.32 vs 9.88±6.77; p=0.004; SF-36 QoL score: 78.6±6.44 vs 53.1±4.72; p<0.001). No serious adverse event was reported. CONCLUSIONS: Compared with placebo, HA-CS intravesical instillations significantly reduced UTI rate without severe side effects while improving symptoms and QoL over a 12-mo period in patients with recurrent UTI. TRIAL REGISTRATION: ISRCTN 76354426.