Background Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). No therapy currently halts disease progression. The strong gut–liver axis implicated in PSC pathogenesis supports the investigation of microbiome-targeted treatments. Oral vancomycin (OV), an antibiotic with potential immunomodulatory properties, has shown encouraging results in improving clinical symptoms and liver biochemistry in PSC. However, prospective data on its safety and efficacy remain limited.Methods and analysis Oral Vancomycin for primary sclerosing Cholangitis in ITaly (VanC-IT) is a phase II, dose-finding, randomised, placebo-controlled, trial designed to evaluate the efficacy and safety of OV in patients with PSC, with or without underlying IBD. Adults and adolescents aged 15–75 years will be enrolled following a 10-week screening and run-in period and randomised in a 1:1:1 ratio to receive either placebo, OV 750 mg/day or OV 1500 mg/day for 24 weeks. Randomisation will be stratified by baseline liver stiffness (< or ≥14.4 kPa). Participants will be followed at 4 and 12 weeks post-treatment. The primary efficacy outcome is the change in serum alkaline phosphatase at 24 weeks. Key secondary outcomes will assess the safety, the impact of OV on liver biochemistry, PSC risk scores, circulating and imaging markers of liver disease, IBD activity, quality of life and incidence of PSC-related clinical events. Key translational aims include sequencing of the faecal microbiota, metabolomic profiling of serum and stool samples and immunological profiling of serum associated with OV treatment.Ethics and dissemination The protocol has been approved by the Ethics Committee CE Brianza on 10 February 2023, number 4017. Trial registration number NCT05876182. Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.Trial registration number NCT05876182.

BACKGROUND:Collateral blood flow is a critical determinant of successful recanalization in acute ischemic stroke caused by large vessel occlusion. Head down tilt -15° (HDT15), similar to Trendelenburg positioning, is a simple, low-cost positional therapy that may augment cerebral collateral blood flow and penumbral survival. The aim of the study is to assess the safety, feasibility, and efficacy of HDT15 in improving cerebral collateral circulation and clinical outcomes in patients with large vessel occlusion-acute ischemic stroke treated with mechanical thrombectomy (MT). METHODS:The DOWN-SUITE trial (Head Down Tilt 15° to Increase Collateral Flow in Acute Ischemic Stroke) is a multicenter, randomized, open-label, phase 2a/b clinical trial with blinded outcome assessment, conducted across 7 Italian stroke centers. A total of 118 patients with acute ischemic stroke due to M1 segment middle cerebral artery occlusion will be randomized 1:1 in the emergency department to receive HDT15 or standard positioning (head-of-bed 0° to +30°) before and during MT. RESULTS:The primary end point is good collateral status (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grade 3-4), assessed on the first angiographic sequence during MT by a blinded imaging core laboratory. Secondary end points include feasibility (proportion maintaining HDT15, admission-to-MT time), safety (symptomatic intracranial hemorrhage, pneumonia, vomiting, neurological deterioration, vital signs), and efficacy (neurological improvement before MT, at 24 hours, and at 7 days or discharge, modified Rankin Scale score at 90 days). CONCLUSIONS:The DOWN-SUITE trial will provide evidence on the acute cerebrovascular effect of HDT15 in large vessel occlusion-acute ischemic stroke, potentially establishing a cost-effective, practice-changing intervention to improve collaterals for global stroke care. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06297863.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating toxicity of many drugs used in cancer treatment. There are numerous available strategies for preventing or treating CIPN, but few are guideline-recommended, due to limited evidence of their effectiveness. The primary objective of this survey was to understand what strategies patients used to prevent or treat CIPN, and to understand their perceptions around CIPN prevention and treatment. Methods: The Multinational Association of Supportive Care in Cancer (MASCC) Neurological Complications Study Group created a cross-sectional online survey to recruit individuals who are currently or had previously received neurotoxic chemotherapy treatment and self-reported peripheral neuropathy. Descriptive statistics were reported. Results: Most of the 447 survey participants did not use any CIPN prevention strategy (71%), though given options of any strategy the plurality preferred a prescribed medication or supplement (30%). The most common treatment strategy used was exercise (47%), with some patients trying prescription medications including non-guideline recommended gabapentin (33%) or guideline-recommended duloxetine (8%) options. Nearly half of participants (49%) used at least one non-prescribed medication for treating CIPN. Patient’s often followed suggestions of their medical oncology clinical team, but sometimes relied on the internet or other patients to recommend non-prescription strategies. Conclusion: In the absence of many guideline-recommended strategies for CIPN prevention and treatment, some patients use options with minimal evidence of effectiveness. Additional research is needed to determine which strategies are effective for prevention and treatment so these can be implemented in practice to improve treatment outcomes in patients with cancer.

BACKGROUND AND PURPOSE:CDK 4/6 inhibitors with ET are the recommended choice as 1st-line therapy in HR+/HER2- MBC patients, however ET alone could remain an option for some of them. HERMIONE-7 is a multicenter, single-arm, Phase II study, aimed to evaluate Abemaciclib 150 mg BID + AIs, in patients who progressed on 1st line Fulvestrant. MATERIALS AND METHODS:Primary aim was the efficacy of Abemaciclib + AIs in terms of Clinical Benefit Rate (CBR), secondary aims were Time to Progression (TTP), Overall Response Rate (ORR), duration of response (DOR), and safety. RESULTS:From April 2020 to January 2022, we enrolled 31 patients. Median age was 72 years (range 47-86), 55% had < 2 comorbidities, mainly hypertension (12, 38.7%). Clinical Benefit Rate was 69% (95% CI, 49-85) and ORR was 21% (95%CI, 8-40). 1-year TTP and OS rates were 53.8% (95% CI, 38.6-74.9%) and 69.5% (95% CI, 54.8%-88.5%), respectively. Main adverse events remain diarrhea (80.6%), fatigue (54.8%) and nausea (35.5%), 3 patients (10.7%) had non drug-related fatal events. CONCLUSIONS:HERMIONE-7 study showed that 2nd-line treatment with Abemaciclib + AIs is a feasible option in MBC patients who progressed on Fulvestrant in 1st-line setting and could be an alternative especially in terms of optimizing the cost-benefit ratio in some Countries.

The aims of the study were: comparing the strength of the thigh muscles at 30°/s and 60°/s, comparing the hamstring to quadriceps ratio (H/Q) resulting from the two movement velocities, and calculating an optimum cut-off for H/Q at 30°/s. The study involved both legs of 29 healthy non-professional athletes aged 20 to 30 years, resulting in a total sample size of 58 legs. Maximum concentric torques and H/Q ratios were measured at angular velocities of 30°/s and 60°/s, with five repetitions per leg and a 60-s rest between phases. The statistical analysis included descriptive and inferential tests (Wilcoxon, T-test, Pearson correlation, linear regression model, receiver operating characteristics (ROC) analyses and agreement test), with statistical p-value significance set at 0.05. At 30°/s, quadriceps and hamstring torques were higher compared to 60°/s, but there was no significant difference in the resulting H/Q. We found a positive correlation between the H/Q ratios at the two speeds (Pearson’s r = 0.796). Age, sex, body mass index (BMI), dominant leg, or activity level did not influence this ratio at 30°/s and at 60°/s. ROC models and agreement tests suggested an optimal cut-off value of 0.57 at 30°/s. Operating at the 30°/s velocity generated higher peak torques, while it maintained H/Q comparable to that obtained at the 60°/s velocity. This lower speed may make the isokinetic test more feasible during rehabilitation after ACL reconstruction surgery, especially for patients who struggle with a 60°/s test. However, when using 30°/s, the conventional H/Q cut-off should be set at 0.57.

Abstract BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard of care for hormone receptor-positive (HR+)/Human Epidermal Growth Factor 2 negative (HER2-) metastatic breast cancer (MBC); no consensus actually exists for second-line (2L) treatments. The HERMIONE-13 trial evaluates the adopted therapeutic options after CDK4/6i failure and the potential factors that influence these choices. METHODS: HERMIONE-13 is a retrospective and prospective multicentric observational trial involving 15 Italian Centers. Information about therapies after disease progression to CDK4/6i from January 2016 until December 2020 was collected for the present analysis, aiming at evaluating which are the clinical criteria guiding the choice of 2L therapy after CDK4/6i failure. RESULTS: 114 pts have been enrolled: 14 pts (12.3%) received neoadjuvant treatment, 80 (70.2%) adjuvant therapy, of whom 46 (57.5%) chemotherapy (CT)+ endocrine therapy (ET) and 33 (41.3%) ET alone. Among the 79 pts treated with adjuvant ET, 44 pts (55.7%) showed primary or secondary endocrine resistance. 39 pts (34.2%) received first-line (1L) CDK 4/6i in combination with Fulvestrant (F), the remaining with aromatase inhibitors (AIs). Median duration of 1L CDK4-6i was 10.4 months (interquartile range (IQR) 4.7-17.4). Median age at 2L start was 59.5 years (IQR 51-68). As 2L therapy, 79 pts (69.3%) received CT±targeted therapy (TT) and 35 (30.7%) ET±TT. Visceral metastases at the beginning of 2L were documented in 46 pts (40.4%). Comorbidities were present in 48 (42.9%) of the pts, mainly cardiac diseases (25, 22.3%); 71 pts (63.4%) showed a 1L-related adverse events (AEs) (NA: 2 pts), mainly hematological toxicity (60, 53.6%). Among 79 pts treated with adjuvant ET, 60 (76%) were addressed to 2L CT±TT, while 19 (24%) to an ET-based therapy. A longer duration of 1L was observed in pts treated with 2L ET±TT (12.5 months, 7.2-22.2) in comparison with those treated with CT±TT (8.7 months, 4.2-14.9). The majority of pts treated with 1L F+CDK 4/6i underwent 2L CT-based treatment, as summarized in Table 1. Analyzing the population treated with 2L CT±TT, we observed that median age was 58 years (49-67), slightly lower than that of pts treated with ET±TT (63, 54-69). Among pts with visceral metastases, 30 pts (65.2%) were addressed to 2L CT±TT and 16 pts (34.8%) to ET±TT; CT±TT was also the favorite choice for the majority of pts with concomitant disease (33, 68.8%) and with previous CDK4/6i-related toxicity (47, 66.2%). Among age, visceral metastases, comorbidities, adjuvant treatment, duration of 1L therapy, use of 1L F and 1L related AEs, univariate analysis revealed that previous use of adjuvant ET (p=0.021), 1L F (p< 0.001), duration of 1L treatment (p=0.043) and age at 2L start (p=0.053) are all factors influencing the choice of 2L therapy. At the multivariate logistic regression model, only the use of F in association with CDK4/6i as 1L treatment and age at 2L therapy were associated with the choice between ET±TT vs CT± TT, with a backward selection, as summarized in table 2. CONCLUSION: The preliminary results of our study suggest that previous F in combination with CDK4/6i is a statistically confirmed predictor of choice for subsequent CT, whereas the increase in age is significantly associated with the choice for ET. Further research is needed to investigate the optimal sequencing of treatments following CDK4/6i and to determine predictive factors of response to 2L therapies. Table 1 2L choices in 1L F+CDK 4/6i pts. Table 2 Statistical model with the significant variables. Citation Format: Marina Elena Cazzaniga, Emanuela Rossi, Antonella Turla, Massimo Ambroggi, Alice Baggi, Rossana Berardi, Fulvio Borella, Serena Capici, Federica Cicchiello, Luigi Coltelli, Ugo De Giorgi, Antonella Ferro, Ornella Garrone, Monica Giordano, Elisabetta Landucci, Marco Mazzotta, Gabriella Moretti, Raffaella Palumbo, Francesca Fulvia Pepe, Patrizia Vici, Fable Zustovich, Viola Cogliati. Selection criteria for second-line treatments after Cyclin-dependent kinase 4/6 inhibitors failure in Hormone Receptor positive metastatic breast cancer patients: the preliminary experience of the HERMIONE-13 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-10.

BACKGROUND AND PURPOSE:Chemotherapy-induced peripheral neuropathy (CIPN) is perceived differently by patients and physicians, complicating its assessment. Current recommendations advocate combining clinical and patient-reported outcomes measures, but this approach can be challenging in patient care. This multicenter European study aims to bridge the gap between patients' perceptions and neurological impairments by aligning both perspectives to improve treatment decision-making. METHODS:Data were pooled from two prospective studies of subjects (n = 372) with established CIPN. Patient and physician views regarding CIPN were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Total Neuropathy Scale-clinical version (TNSc) items, and the disease-specific quality of life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20) from the European Organization for Research and Treatment of Cancer (EORTC). To identify inherent neurotoxic severity patterns, we employed hierarchical cluster analysis optimized with k-means clustering and internally validated by discriminant functional analysis. RESULTS:Both NCI-CTCAE and TNSc demonstrated a significant difference in the distribution of severity grades in relation to QLQ-CIPN20 scores. However, a proportion of subjects with different neurotoxic severity grades exhibited overlapping QLQ-CIPN20 scores. We identified three distinct clusters classifying subjects as having severely impaired, intermediately impaired, and mildly impaired CIPN based on TNSc and QLQ-CIPN20 scores. No differences in demographics, cancer type distribution, or class of drug received were observed. CONCLUSIONS:Our results confirm the heterogeneity in CIPN perception between patients and physicians and identify three well-differentiated subgroups of patients delineated by degree of CIPN impairment based on scores derived from TNSc and QLQ-CIPN20. A more refined assessment of CIPN could potentially be achieved using the calculator tool derived from the cluster equations in this study. This tool, which facilitates individual patient classification, requires prospective validation.

Abstract Background Post-COronaVIrus Disease 2019 (COVID-19) conditions (PCC) include multiple symptoms afflicting different organs and systems. To evaluate the frequency and type of them, we described our multidisciplinary approach with preliminary results of the first enrolled patients. Methods We included patients aged ≥ 18 years with hospital admission for confirmed SARS-CoV-2 infection. Symptoms were grouped in five macro groups hereafter referred to as "Symptoms Category" (SC): respiratory SC (dyspnoea or cough), neurological SC (peripheral neuropathies, headache, impaired mobility, behavioural disorders), psychological SC (sleep disorders, mood disorders), muscular SC (arthromyalgia, asthenia), other SC (fever, alopecia, diarrhoea, weight loss, smell and taste alterations, sexual dysfunctions). SC were evaluated at discharge and at follow-up. Association between patients’ characteristics and presence of SC at follow up was estimated by a logistic multivariable regression model. Results From June 2020 to July 2021, we followed up 361 patients: 128 (35.5%) who were previously admitted to Intensive Care Unit (ICU) and 233 patients to ordinary department. The median length of hospital stay was 20 days (Inter-Quartile-Range 13–32). Most patients (317/361, 87.8%) were still symptomatic at discharge, with one third referring three or more SC. At follow up, 67.3% (243/361) of patients still complained at least one SC. Moreover, 159 patients (44%) developed at least one new involved SC during follow up: 116 (72.9%) one SC, 39 (24.5%) two SC, 4 (2.5%) three or more SC. At follow up visit 130 of 361 (36%) were still with SC developed during follow up. At multivariable analysis presence of any SC at follow-up was associated with male gender (Odds Ratio [OR] 3.23, Confidence Interval [CI] 95% 1.46–7.15), ICU admission (OR 2.78, CI 95% 1.29–5.96) and presence of SC at discharge (OR 14.39, CI 95% 6.41–32.32). Conclusions In our sample of patients with severe COVID-19, we found that PCC are highly variable and fluctuating over time; in particular, in about 50% of our patients new SC appear during follow up. Moreover, presence of PCC also in patients without SC at discharge and the variability of symptoms underlining the advisability of our multidisciplinary approach. Trial registration number: ClinicalTrials.gov Identifier: NCT04424992, registered on 28 February 2020 https://www.clinicaltrials.gov/ct2/results?recrs=ab&cond=&term=NCT04424992&cntry=&state=&city=&dist The current version of protocol is version 1.0 enrolling since June 2020. The enrollment is still ongoing.

Purpose Clinical practice guidelines recommend altering neurotoxic chemotherapy treatment in patients experiencing intolerable chemotherapy-induced peripheral neuropathy (CIPN). The primary objective of this survey was to understand patient’s perspectives on altering neurotoxic chemotherapy treatment, including their perceptions of the benefits of preventing irreversible CIPN and the risks of reducing treatment efficacy. Methods A cross-sectional online survey was distributed via social networks to patients who were currently receiving or had previously received neurotoxic chemotherapy for cancer. Survey results were analyzed using descriptive statistics and qualitative analysis. Results Following data cleaning, 447 participants were included in the analysis. The median age was 57 years, 93% were white, and most were from the UK (53%) or USA (38%). Most participants who were currently or recently treated expected some CIPN symptom resolution (86%), but 45% of those who had completed treatment more than a year ago reported experiencing no symptom resolution. Participants reported that they would discontinue chemotherapy treatment for less severe CIPN if they knew their symptoms would be permanent than if symptoms would disappear after treatment. Most patients stated that the decision to alter chemotherapy or not was usually made collaboratively between the patient and their treating clinician (61%). The most common reason participants were reluctant to talk with their clinician about CIPN was fear that treatment would be altered. Participants noted a need for improved understanding of CIPN symptoms and their permanence, better patient education relating to CIPN prior to and after treatment, and greater clinician understanding and empathy around CIPN. Conclusions This survey highlights the importance of shared decision-making, including a consideration of both the long-term benefits and risks of altering neurotoxic chemotherapy treatment due to CIPN. Additional work is needed to develop decision aids and other communication tools that can be used to improve shared decision making and help patients with cancer achieve their treatment goals.

Short- and medium-term cardio-pulmonary sequelae after COVID-19 have been extensively studied. However, studies with longer follow-ups are required. This study aims to identify and characterise cardio-pulmonary sequelae, in patients hospitalised for SARS-CoV-2 pneumonia, at 24 months follow-up. This is a prospective, observational cohort study conducted on consecutive patients hospitalised for COVID-19 and acute respiratory failure. Patients were followed up at 24 months with complete pulmonary function tests (PFTs), 6-min walking test and a dyspnoea score (Modified Medical Research Council scale). A subgroup of patients with at least one clinical or functional sign suggestive of increased pulmonary pressures also underwent transthoracic echocardiography (TTE) to evaluate the presence of direct or indirect signs of pulmonary hypertension (PH). Ninety consecutive patients (74% men, median age 59.1 years) were enrolled in the study. In regard to PFTs, carbon monoxide diffusion capacity (DLCO) impairment was observed in 23 cases (26%), in all cases of mild entity. When considering the dyspnoea, 30 (34%) patients showed some degree of breathlessness. Forty patients underwent TTE. No patients had overt PH or chronic thromboembolic PH. However, all patients showed a hyperdynamic state of the right ventricle, and 8 (20%) patients had a decreased acceleration time on pulmonary valve, signs of increased pulmonary vasculature resistances and afterload elevation. At 24-month follow-up after severe COVID-19, DLCO and TTE prove to be the most sensitive tool to detect cardio-pulmonary sequelae. Dyspnoea is still present in about one-third of patients and requires a multidisciplinary approach.

BACKGROUND/OBJECTIVES:High-risk Hodgkin lymphoma (HRHL) in children is curable with combined modality therapy. The Association of Pediatric Hematology-Oncology of Central America (AHOPCA) is a consortium of cancer centers from Central America. In 2004, AHOPCA implemented a guideline with a short course of chemotherapy (mStanfordV), strict diagnostics, and radiation guidelines, aimed at reducing abandonment and improving outcomes.METHODS:Newly diagnosed children less than 18 years of age with high-risk HL (Ann Arbor stages: IIB, IIIB, IV) from AHOPCA centers were staged with chest radiography and ultrasound or computed tomography. Therapy was a modified Stanford V (mStanfordV), substituting cyclophosphamide for mechlorethamine and involved field radiation.RESULTS:Of 219 patients with HRHL, 181 patients were eligible and evaluable; 146 (81%) were boys, 22% being less than 6 years; 43 were stage IIB, 84 IIIB, and 54 IV. Thirty-one (17%) abandoned therapy, 28 (15%) progressed, 30 (17%) relapsed, and eight (4%) died of toxicity. Radiation guidelines were not followed. Five-year abandonment-sensitive event-free survival and overall survival (AS-EFS, AS-OS ± SE) for the cohort were 46% ± 4% and 56% ± 4%; 5-year AS-OS for stages IIB, IIIB, and IV was 76% ± 7%, 59% ± 7%, and 35% ± 7% (p = .0006).CONCLUSION:Despite instituting a short treatment guideline, it did not improve the abandonment rate (17%) and did not achieve the reported outcomes of Stanford V. The cyclophosphamide dose used to replace merchlorethamine was inadequate. Despite strict guidelines, the radiation therapy application was inaccurate. Weekly chemotherapy may have adversely affected abandonment of therapy by increasing the burden of travel time. Based on these results, AHOPCA established a new abandonment strategy and a new guideline.

Introduction: There is a paucity of knowledge about the effects of COVID-19 on long-term frailty development or progression over time.Objective: This longitudinal panel study aimed to assess transitions in frailty status in patients who survived hospitalization after acute respiratory failure due to COVID-19.Methods: A multidisciplinary outpatient follow-up service was established for the evaluation of individuals who survived hospitalization after acute respiratory failure due to COVID-19. Frailty status was assessed in-hospital and at follow-up using the Clinical Frailty Scale (CFS). The assessment was obtained by an intensivist for patients admitted to the Intensive Care Unit or by a geriatrician for those admitted to medical wards. Principal patients’ characteristics, including socio-demographic, cognition, functional status, comorbidities and ventilatory support, were collected.Results: Four hundred-fifty patients were evaluated until September 2021. The median follow-up time was 4.2 (Q1-Q3 3.2-6.5) months. Patients were predominantly male, with a median age of 59 (Q1-Q3 53-68) years and a median Body Mass Index of 28.3 (Q1-Q3 25.5-31.5) kg/m² at hospital admission. One hundred and ninety patients (42.2%) scored worse at follow-up compared to hospitalization, and 50 patients (12%) became vulnerable or frail.Conclusions: This study shows that nearly one in two patients previously hospitalized for COVID-19 had an unfavorable transition in CFS score during a median follow-up of nearly 4 months. Specific interventions to prevent frailty development or progression should be considered for patients surviving hospitalization after acute respiratory failure due to COVID-19.

There is a paucity of knowledge about the effects of COronaVIrus Disease-19 (COVID-19) on long-term frailty development or progression over time. This study aims to assess transitions in frailty status in older adults who survived hospitalization for COVID-19. This is a longitudinal panel study. A multidisciplinary outpatient follow-up service was established since summer 2020, for the evaluation of individuals discharged alive, after hospitalization due to COVID-19. Frailty status was assessed in-hospital and at follow-up using the clinical frailty scale (CFS). Main patients’ characteristics, including health, functional, cognitive, and psychological status were collected. A total of 177 patients aged 65 years and older were evaluated until June 2022. They were predominantly male, with a median age of 70 (Q1–Q3 67–75) years and a median body mass index of 27.5 (Q1–Q3 24.9–30.6) kg/m2 at hospital admission. The median follow-up time was 6.3 (Q1–Q3 3.7–10.9) months. Sixty-one patients (34.5

OBJECTIVES:Delirium is commonly seen in older adults with multimorbidity, during a hospitalization, resulting from the interplay between predisposing factors such as advanced age, frailty, and dementia, and a series of precipitating factors. The association between delirium and specific multimorbidity is largely unexplored so far although of potential key relevance for targeted interventions. The aim of the study was to check for a potential association of multimorbidity with delirium in a large cohort of older patients hospitalized for an acute medical or surgical condition.DESIGN:This is a cross-sectional study nested in the 2017 Delirium Day project.SETTING AND PARTICIPANTS:The study includes 1829 hospitalized patients (age: 81.8, SD: 5.5). Of them, 419 (22.9%) had delirium.METHODS:Sociodemographic and medical history were collected. The 4AT was used to assess the presence of delirium. The Charlson Comorbidity index was used to assess multimorbidity.RESULTS:The results identified neurosensorial multimorbidity as the most prevalent, including patients with dementia, cerebrovascular diseases, and sensory impairments. In light of the highest co-occurrence of 3 neurosensorial chronic conditions, we could hypothesize that a baseline altered brain functional and neural connectivity might determine the vulnerability signature for incipient overall system disruption in presence of acute insults.CONCLUSIONS AND IMPLICATIONS:Eventually, our findings moved a step forward in supporting the key importance of routine screening for sensory impairments and cognitive status of older patients for the highest risk of in-hospital delirium. In fact, preventive interventions could be particularly relevant and effective in preventing delirium in such vulnerable populations and might help refining this early diagnosis.

Understanding the cause of sex disparities in COVID-19 outcomes is a major challenge. We investigate sex hormone levels and their association with outcomes in COVID-19 patients, stratified by sex and age. This observational, retrospective, cohort study included 138 patients aged 18 years or older with COVID-19, hospitalized in Italy between February 1 and May 30, 2020. The association between sex hormones (testosterone, estradiol, progesterone, dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19, in-hospital mortality) was explored in 120 patients aged 50 years and over. STROBE checklist was followed. The median age was 73.5 years [IQR 61, 82]; 55.8% were male. In older males, testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L, p =0.0378 and 3.7 vs. 8.5 nmol/L, p =0.0011, respectively). Deceased males had lower testosterone (2.4 vs. 4.8 nmol/L, p =0.0536) and higher estradiol than survivors (40 vs. 24 pg/mL, p = 0.0006). Testosterone was negatively associated with ARDS (OR 0.849 [95% CI 0.734, 0.982]), severe COVID-19 (OR 0.691 [95% CI 0.546, 0.874]), and in-hospital mortality (OR 0.742 [95% CI 0.566, 0.972]), regardless of potential confounders, though confirmed only in the regression model on males. Higher estradiol was associated with a higher probability of death (OR 1.051 [95% CI 1.018, 1.084]), confirmed in both sex models. In males, higher testosterone seems to be protective against any considered outcome. Higher estradiol was associated with a higher probability of death in both sexes.

BackgroundPTX3 is an important mediator of inflammation and innate immunity. We aimed at assessing its prognostic value in a large cohort of patients hospitalized with COVID-19.MethodsLevels of PTX3 were measured in 152 patients hospitalized with COVID-19 at San Gerardo Hospital (Monza, Italy) since March 2020. Cox regression was used to identify predictors of time from admission to in-hospital death or mechanical ventilation. Crude incidences of death were compared between patients with PTX3 levels higher or lower than the best cut-off estimated with the Maximally Selected Rank Statistics Method.ResultsUpon admission, 22% of the patients required no oxygen, 46% low-flow oxygen, 30% high-flow nasal cannula or CPAP-helmet and 3% MV. Median level of PTX3 was 21.7 (IQR: 13.5-58.23) ng/ml. In-hospital mortality was 25% (38 deaths); 13 patients (8.6%) underwent MV. PTX3 was associated with risk of death (per 10 ng/ml, HR 1.08; 95%CI 1.04-1.11; P<0.001) and death/MV (HR 1.04; 95%CI 1.01-1.07; P=0.011), independently of other predictors of in-hospital mortality, including age, Charlson Comorbidity Index, D-dimer and C-reactive protein (CRP). Patients with PTX3 levels above the optimal cut-off of 39.32 ng/ml had significantly higher mortality than the others (55% vs 8%, P<0.001). Higher PTX3 plasma levels were found in 14 patients with subsequent thrombotic complications (median [IQR]: 51.4 [24.6-94.4] versus 21 [13.4-55.2]; P=0.049).ConclusionsHigh PTX3 levels in patients hospitalized with COVID-19 are associated with a worse outcome. The evaluation of this marker could be useful in prognostic stratification and identification of patients who could benefit from immunomodulant therapy.

Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the “Delirium Day project”. We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the “Delirium Day project” (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. Delirium was detected in 226 patients (18%), and the most recurrent motor subtype was mixed (37%), followed by hypoactive (26%), hyperactive (21%) and non-motor one (16%). In a multivariate Poisson regression model with robust variance, factors associated with delirium were: disability in basic (PR 1.48, 95%CI: 1.17–1.9, p value 0.001) and instrumental activities of daily living (PR 1.58, 95%CI: 1.08–2.32, p value 0.018), dementia (PR 2.10, 95%CI: 1.62–2.73, p value < 0.0001), typical antipsychotics (PR 1.47, 95%CI: 1.10–1.95, p value 0.008), antidepressants other than selective serotonin reuptake inhibitors (PR 1.3, 95%CI: 1.02–1.66, p value 0.035), and physical restraints (PR 2.37, 95%CI: 1.68–3.36, p value < 0.0001). This multicenter study reports that 2 out 10 patients admitted to rehabilitations had delirium on the index day. Mixed delirium was the most prevalent subtype. Delirium was associated with unmodifiable (dementia, disability) and modifiable (physical restraints, medications) factors. Identification of these factors should prompt specific interventions aimed to prevent or mitigate delirium.

Patients receiving N-acetyl-l-cysteine (NAC) during hospitalisation for #SARSCoV2 pneumonia and discharged alive present a significantly shorter length of hospital stay compared to those who did not receive NAC https://bit.ly/3l1QsVo.