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One of the main issues in the treatment of patients with chronic lymphocytic leukemia (CLL) deals with the choice between continuous or fixed-duration therapy. Continuous ibrutinib (IB), the first-in-class BTK inhibitor, and obinutuzumab-chlorambucil (G-CHL) are commonly used therapies for elderly and/or comorbid patients. No head-to-head comparison has been carried out. Within the Italian campus CLL network, we performed a retrospective study on CLL patients without TP53 disruption treated with IB or G-CHL as first-line therapy. Patients in the G-CHL arm had a higher CIRS score and the worst renal function. The overall response rates between the G-CHL and IB arms were similar, but more complete remissions (CRs) were achieved with G-CHL (p = 0.0029). After a median follow-up of 30 months, the progression-free survival (PFS, p = 0.0061) and time to next treatment (TTNT, p = 0.0043), but not overall survival (OS, p = 0.6642), were better with IB than with G-CHL. Similar results were found after propensity score matching and multivariate analysis. While PFS and TTNT were longer with IB than with G-CHL in IGHV unmutated patients (p = 0.0190 and 0.0137), they were superimposable for IGHV mutated patients (p = 0.1900 and 0.1380). In the G-CHL arm, the depth of response (79% vs. 68% vs. 38% for CR, PR and SD/PD; p < 0.0001) and measurable residual disease (MRD) influenced PFS (78% vs. 53% for undetectable MRD vs. detectable MRD, p = 0.0203). Hematological toxicities were common in the G-CHL arm, while IB was associated with higher costs. Although continuous IB provides better disease control in CLL, IGHV mutated patients and those achieving an undetectable MRD show a marked clinical and economic benefit from a fixed-duration obinutuzumab-based treatment.

The sequencing of cell-free fetal DNA in the maternal plasma through non-invasive prenatal testing (NIPT) is an accurate genetic screening test to detect the most common fetal aneuploidies during pregnancy. The extensive use of NIPT, as a screening method, has highlighted the limits of the technique, including false positive and negative results. Feto-placental mosaicism is a challenging biological issue and is the most frequent cause of false positive and negative results in NIPT screening, and of discrepancy between NIPT and invasive test results. We are reporting on two cases of feto-placental mosaicism of trisomy 21, both with a low-risk NIPT result, identified by ultrasound signs and a subsequent amniocentesis consistent with a trisomy 21. In both cases, after the pregnancy termination, cytogenetic and/or cytogenomic analyses were performed on the placenta and fetal tissues, showing in the first case a mosaicism of trisomy 21 in both the placenta and the fetus, but a mosaicism in the placenta and a complete trisomy 21 in the fetus in the second case. These cases emphasize the need for accurate and complete pre-test NIPT counselling, as well as to identify situations at risk for a possible false negative NIPT result, which may underestimate a potential pathological condition, such as feto-placental mosaicism or fetal trisomy. Post-mortem molecular autopsy may discriminate between placental, fetal and feto-placental mosaicism, and between complete or mosaic fetal chromosomal anomalies. A multidisciplinary approach in counselling, as well as in the interpretation of biological events, is essential for the clarification of complex cases, such as feto-placental mosaicisms.

Parkinson's disease (PD) manifestations can include visual hallucinations and illusions. Recent findings suggest that the coherent integration of bodily information within an egocentric representation could play a crucial role in these phenomena. Egocentric processing is a key aspect of spatial navigation and is supported by the striatum. Due to the deterioration of the striatal and motor systems, PD mainly impairs the egocentric rather than the allocentric spatial frame of reference. However, it is still unclear the interplay between spatial cognition and PD hallucinations and how different navigation mechanisms can influence such spatial frames of reference. We report the case of A.A., a patient that suffers from PD with frequent episodes of visual hallucinations and illusions. We used a virtual reality (VR) navigation task to assess egocentric and allocentric spatial memory under five navigation conditions (passive, immersive, map, path decision, and attentive cues) in A.A. and a PD control group without psychosis. In general, A.A. exhibited a statistically significant classical dissociation between the egocentric and allocentric performance with a greater deficit for the former. In particular, the dissociation was statistically significant in the “passive” and “attentive cues” conditions. Interestingly in the “immersive” condition, the dissociation was not significant and, in contrast to the other conditions, trends showed better performance for egocentric than allocentric memory. Within the theories of embodiment, we suggest that body-based information, as assessed with VR navigation tasks, could play an important role in PD hallucinations. In addition, the possible neural underpinnings and the usefulness of VR are discussed.

Background: The question of which parameters may be informative on venetoclax outcome in chronic lymphocytic leukemia (CLL) is still unclear. Furthermore, the choice to treat with venetoclax can be challenging in patients with baseline characteristics or comorbidities that may potentially favor some specific adverse events. Objectives: This study was aimed to evaluate whether age, fitness status, patients’/disease characteristics, or concomitant medications may predict outcomes in CLL patients receiving venetoclax. Design: Retrospective observational study. Methods: Impact of age, presence of Cumulative Illness Rating Scale (CIRS) >6 or severe organ impairment (CIRS3+), Eastern Cooperative Oncology Group–Performance Status (ECOG-PS), renal function, and concomitant medications were retrospectively analyzed on treatment management (definitive discontinuation due to toxicity, discontinuation due to toxicity, Tox-DTD; permanent dose reduction, PDR) and survival [progression free survival (PFS), event free survival (EFS), overall survival (OS)] in unselected patients receiving venetoclax monotherapy in common practice. Results: A total of 221 relapsed/refractory patients were included. Tox-DTD and PDR were reported in 5.9% and 21.7%, respectively, and were not influenced by any fitness parameter, age, number or type of concomitant medication, baseline neutropenia, or impaired renal function. None of these factors were associated with tumor lysis syndrome (TLS) development. Age and coexisting conditions had no influence on PFS and EFS. At univariate analysis, OS was significantly shorter only in patients with ECOG-PS >1 ( p 6 ( p = 0.014) or CIRS3+ ( p = 0.031). ECOG-PS >1 retained an independent role only for EFS and OS. While Tox-DTD affected all survival outcomes, no differences in PFS were reported among patients permanently reducing dose or interrupting venetoclax for > 7 days. Conclusion: Clinical outcome with venetoclax is not influenced by comorbidities, patients’ clinical characteristics, or concomitant medications. Differently from other targeted therapies, this demonstrates that, except ECOG-PS, none of the parameters generally considered for treatment choice, including baseline neutropenia or impaired renal function, should rule the decision process with this agent. Anyway, if clinically needed, a correct drug management does not compromise treatment efficacy and may avoid toxicity-driven discontinuations. Plain Language Summary Chapter 1: Why was this study done? Chapter 2: Which are the main findings of the study? Chapter 3: How these findings may impact on clinical practice? Coexisting conditions and concomitant medications do not affect venetoclax management and survival in chronic lymphocytic leukemia • The question of which parameters may be informative on venetoclax outcome in chronic lymphocytic leukemia is still unclear. Furthermore, the choice to treat with venetoclax can be challenging in patients with baseline characteristics or comorbidities that may potentially favor some specific adverse events (e.g. compromised renal function or baseline neutropenia). • In our large series of patients treated outside of clinical trials, we demonstrated that neither age, fitness, comorbidities nor concomitant medications impact on venetoclax management and survival. Importantly, patients presenting with baseline neutropenia or impaired renal function did not have a higher rate of dose reductions or toxicity-driven discontinuations, thus further underlining that venetoclax may be safely administered even in those categories with no preclusions. • Differently from other targeted agents, our data demonstrate that none of the baseline factors commonly considered in treatment decision process retains a role with venetoclax. Finally, permanent dose reductions and temporary interruptions did not adversely impact PFS suggesting that, if clinically needed, a correct drug management should be adopted with no risk of compromising venetoclax efficacy.

Salmonella is one of the most common agents of foodborne illness. The genus Salmonella includes two species (Salmonella bongori and S. enterica) and six subspecies (enterica I, salamae II, arizonae IIIa, diarizonae IIIb, houtenae IV, and indica VI), each of which contains multiple serotypes associated with animal and human infections. The aim of the study was to evaluate the presence of Salmonella spp. in carcasses of food-producing animals and foods in southern Italy and the serovar distribution among different sources. From 2011 to 2021, a total of 12,246 foods and 982 samples from animal carcasses were collected and analyzed. The overall percentage of positive samples was 5.84% (N = 773) and a significant increase in prevalence was observed by comparing the years 2011–2015 (257, 3.27%) and 2016–2021 (516, 9.61%; p < 0.05). The highest percentage of positive food samples was observed in “Meat and Meat Products” (N = 327/2,438, 13.41%) followed by “Fish and fishery products” (N = 115/1,915, 6.01%). In carcasses, the highest percentage of positive samples was reported from broilers (N = 42/81, 51.85%) followed by buffalo (N = 50/101, 49.50%) and pork (N = 140/380, 36.84%). After typing, the isolates were assigned to the species S. enterica and to the subspecies: enterica (N = 760, 98.32%), diarizonae (N = 8, 1.03%), salamae (N = 3, 0.39%) and houtenae (N = 2, 0.26%). S. Infantis was the most frequently detected (N = 177, 24.76%), followed by S. Derby (N = 77, 10.77%), monophasic S. Typhimurium (N = 63, 8.81%), S. Typhimurium (N = 54, 7.55%), and S. Rissen (N = 47, 6.57%). By comparing the sampling period 2011–2015 with that of 2016–2021, an increase in the prevalence of S. Infantis and monophasic S. Typhimurium and a decrease of S. Typhimurium were recorded (p < 0.05). Thus, present data suggest that, despite the implementation of national and European control strategies to protect against Salmonella, the prevalence of this pathogen in southern Italy is still increasing and a change of national control programs to protect against Salmonella are necessary.

Abstract Background Juvenile idiopathic inflammatory myopathies (JIIMs) are a group of heterogenous, acquired, autoimmune disorders that affect the muscle. While the association between IIMs and malignancy has been widely reported in adults, cancer-associated myositis (CAM) is rare in children, so that routine malignancy screening is not generally performed. This report shows a case of severe CAM in a child. Case presentation An 11-years-old girl presented with worsening dyspnea after a 3-weeks history of progressive proximal weakness, myalgia, dysphagia, and weight loss. Her past history was remarkable for a type I Arnold-Chiari malformation associated with an anterior sacral meningocele. Physical examination showed severe hypotony and hypotrophy. Pulse oximetry and blood test showed a type II respiratory failure (SpO2 88%, pCO2 68 mmHg) and increased muscle enzyme levels (CPK 8479 U/L, AST 715 U/L, ALT 383 U/L, LDH 1795 U/L). The patient needed invasive mechanical ventilation. Inflammatory myositis was considered and treatment with intravenous methylprednisolone (30 mg/Kg/day for 3 days followed by 2 mg/Kg/day) and IVIG (1 g/kg/day for 2 days) was started. Muscle biopsy showed endomysial and perimysial necrosis and inflammation. The presence of serum anti-TIF1-γ antibody positivity led to a malignancy screening. Whole-body MRI showed a mature teratoma underneath sacral meningocele and both lesions were surgically removed. Given the histological and clinical severity of the myopathy, mycophenolate (500 mg twice a day) and rituximab (360 mg/m2, 4 weekly infusions) were added. Due to extreme muscular wasting, severe malnutrition and intolerance to enteral feeding the patient needed a transient tracheostomy and parenteral nutrition, followed by physiotherapy, speech therapy and nocturnal non-invasive ventilation. A complete remission was achieved 3 months after. Conclusions Among cancer-associated autoantibodies (CAAs) in adult patients, anti-TIF1-γ carries the highest risk of CAM, which recognizes with a high likelihood a paraneoplastic pathogenesis. In children, anti-TIF1-γ antibody has been associated with severe cutaneous disease, lipodystrophy, and chronic disease course, but not with CAM, which is overall rare in younger patients. Severe onset of a JIIM, especially if anti-TIF1-γ antibody positive, should prompt suspect of a CAM and lead to a screening for malignancy.

Abstract Background Despite an increasing number of available mental health apps in the bipolar disorder field, these tools remain scarcely implemented in everyday practice and are quickly discontinued by patients after downloading. The aim of this study is to explore adherence characteristics of bipolar disorder patients to dedicated smartphone interventions in research studies. Methods A systematic review following PRISMA guidelines was conducted. Three databases (EMBASE, PsychInfo and MEDLINE) were searched using the following keywords: "bipolar disorder" or "mood disorder" or “bipolar” combined with “digital” or “mobile” or “phone” or “smartphone” or “mHealth” or “ehealth” or "mobile health" or “app” or “mobile-health”. Results Thirteen articles remained in the review after exclusion criteria were applied. Of the 118 eligible studies, 39 did not provide adherence characteristics. Among the selected papers, study length, sample size and definition of measures of adherence were strongly heterogeneous. Activity rates ranged from 58 to 91.6%. Conclusion The adherence of bipolar patients to apps is understudied. Standardised measures of adherence should be defined and systematically evaluated in future studies dedicated to these tools.

Introduction Suicide is the most terrible outcome of bipolar disorders (BD). It impacts families and healthcare professionals deeply. Family history of suicide (FHS) is one of its main risk factors, whereas lithium treatment and absence of substance use disorders (SUD) are two of its few modifiable protective factors. Objectives To explore the relationship between FHS and clinical characteristics in BD. We hypothesized that FHS would be associated with less SUD, higher rates of lithium treatment and shorter duration of untreated illness (DUI). Methods Cross-sectional analysis of subjects with BD followed-up in a specialised outpatient unit (Barcelona, October’08-March’18). We described data with measures of frequency, central tendency and dispersion, and we used χ², Fisher’s test and t-tests for comparisons. Results The sample consisted of 83 subjects, 56.6% males, mean age 41.9 years (SD 12.7). 74.7% (n=62) had a diagnosis of BD-I and 25.3% (n=21) of BD-II. 11 subjects (13.3%) had FHS. Those with FHS did not show significant differences in sociodemographic data, DUI (58.5+/-60.4 vs 38.19+/-84.9 months, p=0.341), lithium use (72.7% vs 73.6%, p=0.95) or SUD (27.3% vs 23.6%, p=0.79). There were differences in terms of lifetime suicide attempts (54.5% vs 20.8%, p=0.026), family history of mental disorders (100% vs 69.4%, n=0.032). Conclusions Contrary to our hypothesis, FHS was not associated with the modifiable protective factors against suicide (namely, less SUD and more lithium prescription). Similarly, we did not find an association with earlier access to mental health services at symptom onset (DUP as proxy). Therefore, our results suggest FHS does not modify attitudes towards prevention. Disclosure No significant relationships.

Introduction Recently, several antidepressants, mood stabilizers, and antipsychotics have been suggested to have favorable effects in the treatment of COVID-19. Objectives The aim of this systematic review was to collect evidence from preclinical and clinical studies concerning the scientific evidence for the repurposing of psychotropic drugs in COVID-19 treatment. Methods Two independent authors searched PubMed-MEDLINE, Scopus, PsycInfo, Clinical Trial Registration Site US (ClinicalTrials.gov) databases, and reviewed the reference lists of articles for eligible articles published up to May 31st, 2021. All preclinical and clinical studies on the effect of any psychotropic drug on Sars-CoV-2 or patients with COVID-19 were included. The Newcastle-Ottawa scale was used for the quality assessment of clinical studies. This systematic review adheres to the PRISMA guidelines. Results 22 studies were included in the synthesis: 9 clinical studies, 9 preclinical studies, and 4 computational studies. The use of antidepressants, both SSRI and non-SSRI, was associated with a reduced risk of severe complications of COVID-19. Several antipsychotics showed an increased risk for both Sars-CoV-2 infection and severe complications during COVID-19. Conclusions The current evidence supports a potential anti-SARS-CoV-2 role for several antidepressants, while the evidence on mood stabilizers or antipsychotics remains controversial. Drug repurposing proved highly successful in response to the current pandemic and psychotropic medications are widely used in clinical practice with well-known safety and tolerability profiles, showing antiviral, immunomodulatory, and anti-inflammatory properties, being perfect candidates for possible treatment of COVID-19. Further research will deliver optimized and specific therapeutic tools that will increase the preparedness of health systems for possible future epidemics. Disclosure No significant relationships.

Introduction Mood episodes in bipolar disorder (BD) are still identified with subjective retrospective reports and scales. Digital biomarkers, such as actigraphy, heart rate variability, or ElectroDermal activity (EDA) have demonstrated their potential to objectively capture illness activity. Objectives To identify physiological digital signatures of illness activity during acute episodes of BD compared to euthymia and healthy controls (HC) using a novel wearable device (Empatica´s E4). Methods A pragmatic exploratory study. The sample will include 3 independent groups totalizing 60 individuals: 36 BD inpatients admitted due to severe acute episodes of mania (N=12), depression (N=12), and mixed features (N=12), will wear the E4-device at four timepoints: the acute phase (T0), treatment response (T1), symptoms remission (T2) and during euthymia (T3; outpatient follow-up). 12 BD euthymic outpatients and 12 HC will be asked to wear the E4-device once. Data pre-processing included average downsampling, channel time-alignment in 2D segments, 3D-array stacking of segments, and random shuffling for training/validation sets. Finally, machine learning algorithms will be applied. Results A total of 10 patients and 5 HC have been recruited so far. The preliminary results follow the first differences between the physiological digital biomarkers between manic and depressive episodes. 3 fully connected layers with 32 hidden units, ectified linear activation function (ReLU) activation, 25% dropout rate, significantly differentiated a manic from a depressive episode at different timepoints (T0, T1, T2). Conclusions New wearables technologies might provide objective decision-support parameters based on digital signatures of symptoms that would allow tailored treatments and early identification of symptoms. Disclosure No significant relationships.

“Grottone” is a pasta filata hard cheese produced in Campania region from cow’s milk and characterized by holes formation due to CO2 development by Propionic Acid Bacteria. The contamination of raw milk with butyric acid-producing spore-forming clostridia represent a major concern for cheese producers since clostridia outgrowth may lead to the cheese late blowing defect during ripening. Detection of clostridial endospores in milk before processing and the use of antimicrobial compounds may represent an important control strategy. The present study is aimed to point out the most suitable procedure for the determination of clostridial spores in dairy samples, and to assess the inhibitory activity of several antimicrobial compounds against Cl. sporogenes. Based on results, MPN counts on Bryant and Burkey medium and CFU on RCM proved to be the most suitable protocols for routine testing. By using these procedures clostridial spores were detected in 10 out 13 milk samples and in all cheeses with late blowing defect. Within antimicrobial compounds, sodium nitrate is still the best choice for preventing late blowing, nevertheless a protective culture of Lacticaseibacillus casei proved to be a promising alternative. Nevertheless, the use of this protective culture in six Grottone cheese productions carried out at farm level, led to unsatisfactory results. Holes’ development was hampered likely for an inhibition of the PAB starter and the expected ‘Grouviera-type’ taste was not perceived by panellists. Based on results, the use of protective cultures needs to be contextualized and interactions with starters needs to be evaluated case by case.

The epidemiology of Salmonella Infantis is complex in terms of its distribution and transmission. The continuous collection and analysis of updated data on the prevalence and antimicrobic resistance are essential. The present work aimed to investigate the antimicrobial resistance and the correlation among S. Infantis isolates from different sources through the multiple-locus variable-number of tandem repeat (VNTR) analysis (MLVA). A total of 562 Salmonella strains isolated from 2018 to 2020 from poultry, humans, swine, water buffalo, mussels, cattle, and wild boar were serotyped, and 185 S. Infantis strains (32.92%) were identified. S. Infantis was commonly isolated in poultry and, to a lesser extent, in other sources. The isolates were tested against 12 antimicrobials, and a high prevalence of resistant strains was recorded. S. Infantis showed high resistance against fluoroquinolones, ampicillin, and tetracycline, which are commonly used in human and veterinary medicine. From all S. Infantis isolates, five VNTR loci were amplified. The use of MLVA was not sufficient to understand the complexity of the epidemiological relationships between S. Infantis strains. In conclusion, an alternative methodology to investigate genetic similarities and differences among S. Infantis strains is needed.

With alcohol experiences increasingly shared on social media, this study investigated the construction and understanding of gender norms in alcohol posts: (a) whether stereotypical gender norms prevail across different platforms and message types (b) among adolescents. Focus group interviews with 47 adolescents (Mage = 16.21; SD = 1.22) indicated that social media are important outlets for reproducing stereotypical norms. While sharing alcohol depictions was deemed to be stereotypically female, there were gender differences in the acceptability of sharing certain types of alcohol depictions. As opposed to girls, it was more appropriate for males to depict extreme, negative alcohol behaviors. While girls acknowledged that ephemeral environments enabled them to feel comfortable sharing extreme alcohol behaviors, they carefully negotiated these references by limiting the number of these posts, highlighting female traits in them, and restricting this content to close friends only. Thus, alcohol-related social media posts are more stereotypical than actual drinking experiences, even in more deliberating message types including ephemeral ones. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes, along with various other pathogenic bacteria, may show resistance against a broad spectrum of antibiotics. Evaluating the extent of resistance in harmful microorganisms like Listeria monocytogenes holds significant importance in crafting novel therapeutic strategies to mitigate or combat the rise of infections stemming from antibiotic-resistant bacteria. The present work aims to investigate the occurrence of antimicrobial resistance among Listeria monocytogenes strains in meat products (n = 173), seafood (n = 54), dairy products (n = 19), sauces (n = 2), confectionary products (n = 1), ready-to-eat rice dishes (n = 1), and food-processing environments (n = 19). A total of 269 Listeria monocytogenes strains belonging to eight different serovars were tested against 10 antimicrobials. In the classes of antibiotics, most of the strains were resistant antibiotics belonging to the family of β-lactams (92.94%). High proportions of L. monocytogenes isolates were resistant to oxacillin (88.48%), followed by fosfomycin (85.87%) and flumenique (78.44%). The lowest level of resistance was observed against gentamycin (1.49%). A total of 235 strains (n = 87.36%) showed a profile of multidrug resistance. In conclusion, a high occurrence of resistant and multidrug-resistant strains of Listeria monocytogenes was observed among the examined serotypes isolated from different food sources. This understanding enables the adoption of suitable measures to avert contamination and the spread of resistant bacteria via food. [ABSTRACT FROM AUTHOR]

Abstract Background Despite an increasing number of smartphone apps, such therapeutic tools have not yet consistently demonstrated their efficacy and many suffer from low retention rates. To ensure the development of efficient apps associated with high adherence, we aimed to identify, through a user-centred design approach, patient and physician expectations of a hypothetical app dedicated to depression. Methods We conducted semi-structured interviews with physicians (psychiatrists and general practitioners) and patients who had experienced a major depressive episode during the last 12 months using the focus group method. The interviews were audio recorded, transcribed and analysed using qualitative content analysis to define codes, categories and emergent themes. Results A total of 26 physicians and 24 patients were included in the study. The focus groups showed balanced sex and age distributions. Most participants owned a smartphone (83.3% of patients, 96.1% of physicians) and were app users (79.2% of patients and 96.1% of physicians). The qualitative content analysis revealed 3 main themes: content, operating characteristics and barriers to the use of the app. Expected content included the data collected by the app, aiming to provide information about the patient, data provided by the app, gathering psychoeducation elements, therapeutic tools and functionalities to help with the management of daily life and features expected for this tool. The “operating characteristics” theme gathered aims considered for the app, its potential target users, considered modalities of use and considerations around its accessibility and security of use. Finally, barriers to the use of the app included concerns about potential app users, its accessibility, safety, side-effects, utility and functioning. All themes and categories were the same for patients and physicians. Conclusions Physician and patient expectations of a hypothetical smartphone app dedicated to depression are high and confirmed the important role it could play in depression care. The key points expected by the users for such a tool are an easy and intuitive use and a personalised content. They are also waiting for an app that gives information about depression, offers a self-monitoring functionality and helps them in case of emergency.