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Background: At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population., Methods: AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0-2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m 2 intravenously on day 1 every 21 days) for 6-8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184., Findings: Between Oct 3, 2018, and Jan 7, 2022, 551 patients were randomly assigned to atezolizumab (n=362) or placebo (n=189). Two patients in the atezolizumab group were excluded from all analyses due to lack of consent. Median follow-up was 28·3 months (IQR 21·2-37·6). 81 (23%) patients in the atezolizumab group and 44 (23%) patients in the placebo group had dMMR disease by central assessment. In the dMMR population, median progression-free survival was not estimable (95% CI 12·4 months-not estimable [NE]) in the atezolizumab group and 6·9 months (6·3-10·1) in the placebo group (hazard ratio [HR] 0·36, 95% CI 0·23-0·57; p=0·0005). In the overall population, median progression-free survival was 10·1 months (95% CI 9·5-12·3) in the atezolizumab group and 8·9 months (8·1-9·6) in the placebo group (HR 0·74, 95% CI 0·61-0·91; p=0·022). Median overall survival was 38·7 months (95% CI 30·6-NE) in the atezolizumab group and 30·2 months (25·0-37·2) in the placebo group (HR 0·82, 95% CI 0·63-1·07; log-rank p=0·048). The p value for the interim analysis of overall survival did not cross the stopping boundary; therefore, the trial will continue until the required number of events are recorded. The most common grade 3-4 adverse events were neutropenia (97 [27%] of 356 patients in the atezolizumab group vs 51 [28%] of 185 in the placebo group) and anaemia (49 [14%] vs 24 [13%]). Treatment-related serious adverse events occurred in 46 (13%) patients in the atezolizumab group and six (3%) patients in the placebo group. Treatment-related deaths occurred in two patients (pneumonia in one patient in each group)., Interpretation: Atezolizumab plus chemotherapy increased progression-free survival in patients with advanced or recurrent endometrial carcinoma, particularly in those with dMMR carcinomas, suggesting the addition of atezolizumab to standard chemotherapy as first-line treatment in this specific subgroup., Funding: F Hoffmann-La Roche., Competing Interests: Declaration of interests EB, FG, ER, and SU report grants from Roche to their institution to support the conduct of the study. NC reports personal fees from AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Pfizer, Roche, and Novocure; and grants or research support from GSK and AstraZeneca. KH reports personal fees from AstraZeneca, Chugai, Eisai, MSD/Merck, Taiho, and Takeda; and grants or research support from MSD/Merck, Chugai, Takeda, AstraZeneca, and Daiichi Sankyo. EH reports personal fees from GSK and Clovis. FM reports personal fees from Roche, Eisai, Novartis, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, MSD/Merck, GSK, Clovis, Gilead, Myriad Genetics, Seagen, and Stemline Menarini; grants or research support from Roche; and participation on data safety monitoring or advisory boards for Immutep, Amgen, and Palleos Healthcare. CM reports personal fees from Roche, Novartis, MSD/Merck, AstraZeneca, Pfizer, PharmaMar, ImmunoGen, Daiichi Sankyo, Novocure, BioNTtech, Eisai, and GSK. LF-M reports personal fees from AstraZeneca, GSK, MSD/Merck, Eisai, and Pharma&. YCL reports personal fees from AstraZeneca, and grants or research support from BeiGene. EP reports personal fees from GSK and AstraZeneca. BP reports personal fees from AstraZeneca, GSK, MSD/Merck, and Pharma&. CZ reports personal fees from Roche, Eisai, Novartis, AstraZeneca, Pfizer, QuintilesIMS, Clovis, Eli Lilly, Istituto Gentili, Daiichi Sankyo, Seagen, MSD/Merck, GSK, and Gilead; and grants or research support from Roche, Novartis, AstraZeneca, Pfizer, Eisai, Clovis, Gilead, Seagen, Eli Lilly, Daiichi Sankyo, and MSD/Merck. KT reports personal fees from AstraZeneca, Chugai Pharma, Takeda, MSD/Merck, Nippon Kayaku, Eisai, and Sanofi; and grants or research support from Chugai Pharma. AF reports personal fees from GSK, AstraZeneca, and MSD/Merck. MP reports personal fees from AstraZeneca, Eisai, GSK, and MSD/Merck. MPBG reports personal fees from AstraZeneca, GSK, MSD/Merck, PharmaMar, Clovis Oncology, Eisai, Pharma&, and Kyowa Kirin; and a leadership role for Geico. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: Various prognostic indexes have been proposed to improve physicians' ability to predict survival time in advanced cancer patients, admitted to palliative care (PC) with a survival probably to a few weeks of life, but no optimal score has been identified. The study aims therefore to develop and externally validate a new multivariable predictive model in this setting., Methods: We developed a model to predict short-term overall survival in cancer patients on the basis of clinical factors collected at PC admission. The model was developed on 1020 cancer patients prospectively enrolled to home palliative care at VIDAS Milan, Italy, between May 2018 and February 2020 and followed-up to June 2020, and validated in two separate samples of 544 home care and 247 hospice patients., Results: Among 68 clinical factors considered, five predictors were included in the predictive model, i.e., rattle, heart rate, anorexia, liver failure, and the Karnofsky performance status. Patient's survival probability at 5, 15, 30 and 45 days was estimated. The predictive model showed a good calibration and moderate discrimination (area under the receiver operating characteristic curve between 0.72 and 0.79) in the home care validation set, but model calibration was suboptimal in hospice patients., Conclusions: The new multivariable predictive model for palliative cancer patients' survival (PACS model) includes clinical parameters routinely at patient's admission to PC and can be easily used to facilitate immediate and appropriate short-term clinical decisions for PC cancer patients in the home setting., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Delirium in end-of-life patients is reported to be between 13% and 42% and up to 80% in the terminal phase. It is a serious clinical situation, often a cause of death due to the frequent ineffectiveness of treatments. This study aimed to assess whether and how much precocity of diagnosis, hitherto little considered, could affect the outcomes and prognosis of delirium in palliative care settings., Methods: Patients consecutively admitted to a palliative care unit (PCU) between October 2018 and December 2019, cared for both in hospice and home programs, were analyzed. All patients were subjected to a careful procedure aimed at recognizing the onset of delirium. The first step was the detection of prodromal "sentinel" symptoms related to incoming delirium. PCU staff and family members/caregivers were trained to observe the patients and immediately identify the appearance of even one symptom. The final diagnosis was performed with the 4AT (4 A's test). Patients were then included in the categories of "early" or "slow" diagnosis (cut-off: four hours) depending on the time between sentinel symptom observation and the final diagnosis of delirium., Results: Among 503 admitted patients, 95 developed delirium. Confusion was the most frequent sentinel symptom (49.5%). The early diagnosis was more frequent in hospice than in home care (p-value<0.0001). Delirium was positively resolved in 43 patients, of which 25 with an early diagnosis (p-value=0.038). Time to resolution was shorter in the case of early diagnosis (7.1 vs. 13.7 hours in hospice patients; p-value=0.018). Palliative sedation was performed on 25 patients, but only 8 of them had an early diagnosis., Conclusion: Time of diagnosis was important in determining the clinical outcomes of patients in charge of PCU who experienced delirium. The early diagnosis reduced both mortality and the necessity of palliative sedation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Beretta et al.)

Background and Aims: This living and systematic review aimed to provide an updated summary of the available evidence on pain undertreatment prevalence in patients with cancer; correlations with some potential determinants and confounders were also carried out., Materials and Methods: We updated a systematic review published on 2014, including observational and experimental studies reporting the use of the pain management index (PMI) in adults with cancer and pain, from 2014 to 2020. We conducted searches in PubMed/MEDLINE, Embase, and Google Scholar. We performed univariate and multivariable regression analyses to describe the relationship between PMI and a list of potential explanatory variables., Results: Twenty new papers were identified, yielding a total sample size of 66 studies. The proportion of patients classified as undertreated according to the year of study publication shows a higher decrease from 1994 to 2013 (-13% as relative change) than the most recent years 2014-2020 (-11%). The quality of the included studies has increased over the years (from 80% to 93%). At the multivariable analysis, a statistically significant relationship was confirmed between undertreatment and the year of the publication of the study and with a low-medium economic level of the countries, where the studies were conducted., Discussion: Despite the improvement when compared to the period 1994-2000, still about 40% of the cases identified received an analgesic treatment inadequate to the intensity of pain, according to the PMI. Despite its intrinsic limitations, PMI continues to be widely used, and it could allow a continuous monitoring of pain management across a different mix of studies and patients., (© 2022 World Institute of Pain.)

Delirium occurs in 50-80% of end-of-life patients but is often misdiagnosed. Identification of clinical factors potentially associated with delirium onset can lead to a correct early diagnosis. To this aim, we conducted a prospective cohort study on patients from an Italian palliative care unit (PCU) admitted in 2018-2019. We evaluated the presence of several clinical factors at patient admission and compared their presence in patients who developed delirium and in those who did not develop it during follow-up. Among 503 enrolled patients, after a median follow-up time of 16 days (interquartile range 6-40 days), 95 (18.9%) developed delirium. Hazard ratios (HR) and corresponding 95% confidence intervals were computed using Cox proportional hazard models. In univariate analyses, factors significantly more frequent in patients with delirium were care in hospice, compromised performance status, kidney disease, fever, renal failure, hypoxia, dehydration, drowsiness, poor well-being, breathlessness, and "around the clock" therapy with psychoactive drugs, particularly haloperidol. In multivariate analyses, setting of care (HR 2.28 for hospice versus home care, 95% CI 1.45-3.60; p < 0.001), presence of breathlessness (HR 1.71, 95% CI 1.03-2.83, p = 0.037), and administration of psychoactive drugs, particularly haloperidol (HR 2.17 for haloperidol, 95% CI 1.11-4.22 and 1.53 for other drugs, 95% CI 0.94-2.48; p = 0.048) were significantly associated with the risk of developing delirium. The study indicates that some clinical factors are associated with the probability of delirium onset. Their evaluation in PC patients could help healthcare professionals to identify the development of delirium in those patients in a timely manner., (© 2021. The Author(s).)

A 69-year-old Caucasian man was admitted to our hospital because of myocardial infarction. A central venous catheter (CVC) for infusive therapy was inserted. After two weeks he developed fever, purpura, and knee arthralgia. Hemoculture yielded methicillin-sensitive Staphylococcus aureus. Subsequently, oliguric renal failure, hematuria, and nephrotic range proteinuria were recorded. Renal biopsy showed mesangial proliferation and crescent formation. In an immunofluorescence study, IgA, IgG, and C3 deposition in the mesangium and along arteriolar walls were observed. A diagnosis of Henoch-Schönlein purpura associated with infection caused by CVC was made. After administration of antibiotic and steroid therapy, proteinuria was markedly reduced, renal function improved, and purpura disappeared. The association of HSP with methicillin-resistant Staphylococcus aureus has frequently been reported in the literature. We present here a case of HSP in association with MSSA bacteremia from central venous catheterization, a finding not reported previously.

Diabetic nephropathy (DN) is a complication associated with diabetes, leading to end-stage renal disease (ESRD). Despite significant progress in understanding DN, the cellular mechanisms leading to the renal damage are incompletely defined. In this study, with the aim to identify urine biomarkers for the early renal alterations in type 2 diabetes mellitus (T2D), we performed urinary proteomic analysis of 10 normoalbuminuric patients with T2D, 12 patients with type 2 DN (T2DN), and 12 healthy subjects. Proteins were separated by 2-DE and identified with ESI-Q-TOF MS/MS. Comparing the patients proteomic profiles with those of normal subjects, we identified 11 gradually differently changed proteins. The decreased proteins were the prostatic acid phosphatase precursor, the ribonuclease and the kallikrein-3. Eight proteins were progressively increased in both patients groups: transthyretin precursor, Ig κ chain C region, Ig κ chain V-II region Cum, Ig κ-chain V-III region SIE, carbonic anhydrase 1, plasma retinol-binding protein, β-2-microglobulin precursor, β-2-glycoprotein 1. The proteomic analysis allowed us to identify several increased urinary proteins, not only in T2DN but also in T2D patients in which the microalbuminuria was in the normal range. These patterns of urinary proteins might represent a potential tool for a better understanding of diabetic renal damage., (Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Light chain deposition disease (LCDD) can involve the heart and cause severe heart failure. Cardiac involvement is usually described in the advanced stages of the disease. We report the case of a woman in whom restrictive cardiomyopathy due to LCDD presented with paroxysmal atrial fibrillation., Case Presentation: A 55-year-old woman was admitted to our emergency department because of palpitations. In a recent blood test, serum creatinine was 1.4 mg/dl. She was found to have high blood pressure, left ventricular hypertrophy and paroxysmal atrial fibrillation. An ACE-inhibitor was prescribed but her renal function rapidly worsened and she was admitted to our nephrology unit. On admission serum creatinine was 9.4 mg/dl, potassium 6.8 mmol/l, haemoglobin 7.7 g/dl, N-terminal pro-brain natriuretic peptide 29894 pg/ml. A central venous catheter was inserted and haemodialysis was started. She underwent a renal biopsy which showed kappa LCDD. Bone marrow aspiration and bone biopsy demonstrated kappa light chain multiple myeloma. Echocardiographic findings were consistent with restrictive cardiomyopathy. Thalidomide and dexamethasone were prescribed, and a peritoneal catheter was inserted. Peritoneal dialysis has now been performed for 15 months without complications., Discussion: Despite the predominant tubular deposition of kappa light chain, in our patient the first clinical manifestation of LCDD was cardiac disease manifesting as atrial fibrillation and the correct diagnosis was delayed. The clinical management initially addressed the cardiovascular symptoms without paying sufficient attention to the pre-existing slight increase in our patient's serum creatinine. However cardiac involvement is a quite uncommon presentation of LCDD, and this unusual case suggests that the onset of acute arrhythmias associated with restrictive cardiomyopathy and impaired renal function might be related to LCDD.

An increased free-radical production has been documented during hemodialysis (HD) particularly when bio-incompatible membranes are utilized. These highly reactive free radicals can cause damage through several pathways, one of the best known being lipid peroxidation. Malondialdehyde (MDA) is a product of lipid peroxidation, which can partly be removed by HD due to its low molecular weight and water solubility. Hydroperoxides are predominantly found in lipid substances, and therefore their removal by HD could be difficult. We evaluated the behavior of these two by-products of lipid peroxidation during HD, comparing their behavior in three different membranes, in order to study their reliability as markers of acute oxidative injury. Fifteen stable HD patients were dialyzed with each of the following membranes: cuprophan, polyamide, and polysulfone, three sessions for every membrane. MDA and hydroperoxides were measured pre-HD and then both from the arterial and venous line at 8, 15, 30, and 240 min. During HD with cuprophan membrane MDA decreased significantly in the venous line compared with the arterial line at 8, 15, and 30 min (P < 0.05). At the end of HD, MDA was significantly reduced compared with MDA pre-HD (P < 0.05). Plasma hydroperoxides increased significantly in the venous line compared with the arterial line at 8, 15, 30, and 240 min (P < 0.05). At the end of HD, hydroperoxides had increased significantly as compared with pre-HD (P < 0.05). When the polyamide and polysulfone membranes were used, the behavior of MDA was similar to that found with cuprophan. Hydroperoxides were unchanged during HD using both membranes. MDA is not a reliable marker of acute oxidative injury during HD as it is removed during HD. Hydroperoxide measurement is a better marker of acute oxidative injury during HD.

An increase in conjugated linoleic acid (CLA), a natural fatty acid present in our diet, which possesses anticarcinogenic and antiatherogenic activities in experimental models, has been found in both the plasma and adipose tissue of end-stage chronic renal failure (ESCRF) patients. Increased levels of retinol have also been found in those patients, due to a reduced excretion of the retinol-binding protein. Since retinol is known to influence lipid metabolism, we evaluated whether changes in retinol, CLA, and other fatty acids are correlated in the plasma of CRF patients. We measured CLA, retinol, and unsaturated fatty acids in the plasma of the following groups: (A) 35 ESCRF patients; (B) 20 hemodialysis (HD) patients; (C) 20 healthy controls. Subjects with total cholesterol and/or triglycerides higher than 250 mg/dL were excluded. We found a significant increase in CLA, retinol, palmitoleic (16:1), and oleic (18:1) acids in ESCRF patients. In HD patients we found a similar pattern, however, CLA increase was not significant. No changes were observed in the other fatty acids measured. In the groups of ESCRF and HD patients, a positive correlation between the levels of plasma retinol and CLA, and between retinol and 16:1 was found. These correlations were not detected in controls. The abnormal levels of plasma retinol in CRF patients might partly explain the changes in CLA and 16:1. The influence of retinol levels on these fatty acids might be due to an induction of delta 9 desaturase. In fact, 16:1 is known to be produced, partly, by delta 9 desaturation of palmitic acid. Moreover, the formation of CLA from delta 9 desaturation of vaccenic acid-a trans-monounsaturated fatty acid present in our diet-has recently been demonstrated in humans. Nevertheless, our data do not represent direct evidence supporting an increased delta 9 desaturase activity in CRF patients. Another possible explanation might be a variation in the exogenous intake.

We carried out a perspective study in order to assess the ease of insertion, the type and the incidence of perioperative complications connected with the use of the Laryngeal Mask Airway (LMA). We examined 300 consecutive patients, M/F 261/39, average age 4.2 yrs. (range 0.1-16), ASA I-II, who underwent surgical operations of short or average length not involving the pleural, the oropharyngeal or the peritoneum cavity. The choice about anesthesia was left to the discretion of the anesthesiologist. In 27 cases the position of the LM was controlled through a flexible fiberoptics. In 269 patients (89.6%) the LMA was correctly positioned during the first attempt. In 27 patients (9%), 2 or more attempts were necessary, and in 4 patients (1.4%) it was not possible to set the LMA. No differences of statistical significance were noticed between the different size of LMA, with regards to the facility of insertion. The control through fiberoptics showed a correct position, from an anatomical point of view, in 11 patients (41%), whereas in 13 patients (48%) some signs of partial obstruction were noticed (epiglottis interposing between the opening of LMA and larynx) and in 3 patients (11%) vocal cords are not visible. The following complications took place: laryngeal spasm on induction (2.3%), cough or movements on positioning (2.3%), hypoxia (4.3%), obstruction (1%), laryngeal spasm on awakening (1.7%), trauma (5%) and vomiting (0.3%). No connections were found between the size of LMA and total complications. Nevertheless, cough or movement during positioning and laryngeal spasm on awakening were significantly more frequent with LMA n. 3. In our experience, the LMA proved to be effectual and safe in the control of the airway during elective operations in pediatric surgery.