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Venetoclax (VEN) and hypomethylating agent (HMAs) regimens are emerging as the standard of care for unfit for chemotherapy acute myeloid leukemia (AML) patients, but the safety and feasibility of a total outpatient management have not been fully investigated. Fifty-nine AML patients with active disease received VEN and HMAs. Nineteen out of 59 (32.2%) patients received the first cycle as inpatients, whereas 40/59 (67.8%) patients were treated in the outpatient setting. No significant differences were observed with regard to incidence of adverse events (AEs), including tumor lysis syndrome (TLS), and the 30-day and 60-day mortality was comparable. Notably, an infectious prophylaxis inspired to that adopted during intensive chemotherapy resulted in a low infection rate with a reduced bacterial infections incidence in out- versus hospitalized patients (p .0001). The overall time of hospitalization was significantly shorter in patients who received a total outpatient treatment as compared to those who received the first cycle as inpatients (5.9 vs. 39.7 days, p .0001). Despite the adopted differences in treatment management, the efficacy was similar. These data indicate that a total outpatient management of VEN and HMAs is feasible in AML patients without negatively impacting on treatment efficacy and may yield pharmacoeconomic and quality-of-life benefits.

Nest-sharer avian brood parasites do not evict or otherwise kill host chicks, but instead inflict a range of negative effects on their nestmates that are mediated by interactions between the parasite and host life history traits. Although many of the negative fitness effects of avian brood parasitism are well documented across diverse host species, there remains a paucity of studies that have examined the impacts of parasitism across the entirety of host ontogeny (i.e., from when an egg is laid until independence). More specifically, few studies have examined the impact of brood parasitism on the pre- and post-fledging development, physiology, behavior, and survival of host offspring. To help fill this knowledge gap, we assessed the effects of brood parasitism by Brown-headed Cowbirds (Molothrus ater) across the ontogeny (incubation, nestling, and post-fledging period) of nine sympatrically breeding host species in central Illinois, USA; due to sample sizes, impacts on the post-fledging period were only examined in two of the nine species. Specifically, we examined the impact of brood parasitism on ontogenetic markers including the embryonic heart rate, hatching rate, nestling period length, nest survival, and offspring growth and development. Additionally, in species in which we found negative impacts of cowbird parasitism on host nestmate ontogeny, we examined whether the difference in adult size between parasites and their hosts and their hatching asynchrony positively predicted variation in host costs across these focal taxa. We found that costs of cowbird parasitism were most severe during early nesting stages (reduction in the host clutch or brood size) and were predicted negatively by host size and positively by incubation length. In contrast, we only found limited costs of cowbird parasitism on other stages of host ontogeny; critically, post-fledging survival did not differ between host offspring that fledged alongside cowbirds and those that did not. Our findings (i) highlight the direct costs of cowbird parasitism on host fitness, (ii) provide evidence for when (the stage) those costs are manifested, and (iii) may help to explain why many anti-cowbird defenses of hosts have evolved for protection from parasitism during the laying and incubation stages.

BACKGROUND AND PURPOSE People with multiple sclerosis (PwMS) often report walking limitations even when the gold standard Expanded Disability Status Scale (EDSS) indicates normal walking endurance/autonomy. The present multicenter study on early-stage PwMS aims at analyzing which aspects are associated with patient-reported walking limitations measured with the 12-item Multiple Sclerosis Walking Scale (MSWS-12). METHODS Eighty-two PwMS (EDSS ≤ 2.5) were assessed using the Fullerton Advanced Balance Scale-short (FAB-s), the Fatigue Severity Scale (FSS) and the 6-min Walk Test (6MWT), the latter administered also to 21 healthy subjects. Participants performed the 6MWT wearing three inertial sensors on ankles and trunk. Instrumented metrics describing gait velocity (stride length and frequency) and quality (regularity, symmetry, instability) were computed from sensor data. Fatigue (FSS), balance (FAB-s), walking endurance (6MWT) and instrumented metrics were entered in a multiple regression model with MSWS-12 as dependent variable. RESULTS Gait symmetry, gait instability, fatigue and balance were significantly associated with self-rated walking ability, whilst walking endurance and velocity were not. Fatigue, balance, gait symmetry and instability were more impaired in participants reporting mild-to-moderate (MSMM-PWL , 25 ≤ MSWS-12

Background Extracorporeal photopheresis (ECP) is an effective treatment for graft-vs-host-disease (GvHD). Photopheresis can be performed in offline or inline method. The first uses a conventional cell separator for collection of mononuclear-cells that are photoactivated by a separate device and manually reinfused; the second one involves a dedicated device performing the entire procedure (collection, photoactivation and reinfusion). Study design and methods The objective was to compare the two methods and cell product features to highlight key process, devices performance, and to evaluate ECP clinical response. Patients developing steroid-resistant GvHD underwent ECP as second-line treatment using either inline (Therakos CellEx) or offline system (Terumo BCT Spectra or Optia and UVA PIT system). Data about patients' features, pre-apheresis blood-count, cell product characteristics and clinical response were collected for analysis. Results We evaluated 494 procedures performed on 28 patients from April 2018 to March 2019. The offline procedure allows to achieve greater cell yield, it is characterized by larger processed blood volume, longer runtime, and higher ACD consumption. The inline procedure shows shorter runtime, high mononuclear-cells percentage and low percentage of granulocytes in cell product. We observed a significant difference in cell yields between inline and offline system; furthermore we did not find a significant relationship between cell dose and clinical response. Conclusion Inline ECP is fast, highly automated and productive, making it particularly suitable for ECP treatments. Offline ECP collects high cell yields implying longer procedure and greater operator intervention. Our study did not find a significant relationship between cell dose and GVHD response.

Background COVID‐19 outbreak prompted health centres to reorganize their clinical and surgical activity. In this paper, we show how medical genetics department's activity, in our tertiary pediatric hospital, has changed due to pandemic. Methods We stratified all our scheduled visits, from March 9th through April 30th, and assessed case‐by‐case which genetic consultations should be maintained as face‐to‐face visit, or postponed/switched to telemedicine. Results Out of 288 scheduled appointments, 60 were prenatal consultations and 228 were postnatal visits. We performed most of prenatal consultations as face‐to‐face visits, as women would have been present in the hospital to perform other procedures in addition to our consult. As for postnatal care, we suspended all outpatient first visits and opted for telemedicine for selected follow‐up consultations: interestingly, 75% of our patients’ parents revealed that they would have cancelled the appointment themselves for the fear to contract an infection. Conclusions Spread of COVID‐19 in Italy forced us to change our working habits. Given the necessity to optimize healthcare resources and minimize the risk of in‐hospital infections, we experienced the benefits of telegenetics. Current pandemic made us familiar with telemedicine, laying the foundations for its application to deal with the increasing number of requests in clinical genetics., In this paper, we show how medical genetics department's activity, in our tertiary pediatric hospital, has changed due to COVID‐19 pandemic. Given the necessity to optimize healthcare resources and minimize the risk of in‐hospital infections, we experienced the benefits of telegenetics. Current pandemic made us familiar with telemedicine, laying the foundations for its application to deal with the increasing number of requests in clinical genetics.

AIMS: Serotonergic (5‐HT) modulation of the lateral habenula (LHb) activity is central in normal and pathologic conditions such as mood disorders. Among the multiple 5‐HT receptors (5‐HTRs) involved, the 5‐HT(2C)R seems to play a pivotal role. Yet, the role of 5‐HT(2A)Rs in the control of the LHb neuronal activity is completely unknown. METHODS: Single‐cell extracellular recording of the LHb neurons was used in rats to study the effect of the general activation and blockade of the 5‐HT(2C)R and 5‐HT(2A)R with Ro 60‐0175 and SB242084, TCB‐2 and MDL11939, respectively. The expression of both receptors in the LHb was confirmed using immunohistochemistry. RESULTS: Cumulative doses (5‐640 μg/kg, iv) of Ro 60‐0175 and TCB‐2 affected the activity of 34% and 63% of the LHb recorded neurons, respectively. LHb neurons were either inhibited at low doses or excited at higher doses of the 5‐HT(2A/C)R agonists. SB242084 or MDL11939 (both at 200 μg/kg, iv) did not modify neuronal firing when injected alone, but reverted the bidirectional effects of Ro 60‐0175 or TCB‐2, respectively. 5‐HT(2C)Rs and 5‐HT(2A)Rs are expressed in less than the 20% of the LHb neurons, and they neither colocalize nor make heterodimers. Strikingly, only 5‐HT(2A)Rs are expressed by the majority of LHb astrocyte cells. CONCLUSIONS: Peripheral administration of 5‐HT(2A)R agonist promotes a heterogeneous pattern of neuronal responses in the LHb, and these effects are more prominent than those induced by the 5‐HT(2C)R activation.

Background Extracorporeal photopheresis (ECP) therapy has proved to be an effective and safe treatment for graft-versus-host-disease (GvHD), an important complication after hematopoietic stem cell transplantation. In 2016, we acquired Therakos CellEx, a dedicated inline ECP device to accomplish a significant increase in ECP activity. In literature, we found few data reporting CellEx performance evaluated in terms of collection efficiency to qualify the device. Hence, we decided to collect and analyze our data in order to build a reference in terms of expected results of the procedure. Here we report our data of ECP performed using CellEx in a 12-month period focusing on collection efficiency assessment, as well as procedural and apheretic product characteristics. Study design and methods We collected data of patients undergoing ECP from April 2018 to March 2019 using CellEx in order to evaluate collection efficiency. Results Between April 2018 and March 2019 we treated 28 adult patients affected by GvHD performing 319 ECP using CellEx. CellEx mononuclear cell product was characterized by high mononuclear cell percentage and low percentage of granulocytes, resulting particularly suitable for ECP treatments. Median collection efficiency for total nucleated cells and for mononuclear cells was 31.2% and 62.3%, respectively. Conclusion Collection efficiency of CellEx was comparable to that usually obtained by cell separators designed for cell collection and was comparable to that of offline systems. Our results provide a detailed performance evaluation for inline ECP system users.

Clinical practice in dystonia has greatly evolved in recent years; a synthetic review on patient management is provided here. Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures or both. A recent classification has innovated clinical practice and serves as guidance for clinical assessment: Axis I describes clinical features, whereas Axis II indicates etiology. Dystonia presents with different syndromic aggregations with varied somatic involvement and some common features. There are five recognizable physical signs of dystonia: two main signs (dystonic postures and movements) and three additional signs (gestes antagonistes or tricks, mirror dystonia and overflow dystonia). There is still no validation of diagnostic criteria for the different dystonia syndromes, and many cases with mild phenomenology remain undiagnosed. Patients with dystonia also present non-motor features that are variably combined with the movement disorder. The features of the most common inherited and acquired dystonia syndromes are reviewed here. There is clear evidence of genetic-environmental interaction in the determinism of dystonia. The diagnostic process is guided by clinical examination and based on specific laboratory examinations. Symptomatic treatments are available for dystonia: botulinum neurotoxin injections are the primary choice for most focal dystonia syndromes; deep brain stimulation is useful in some generalized and non-generalized syndromes. Additional treatment strategies are currently being assessed.

Despite consensus on some neurophysiological hallmarks of the Parkinsonian state (such as beta) band increase) a single mechanism is unlikely to explain the efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN). Most experimental evidence to date correlates with an extreme degree of nigral neurodegeneration and not with different stages of PD progression. It seems inappropriate to combine substantially different patients - newly diagnosed, early fluctuators or advanced dyskinetic individuals - within the same group. An efficacious STN-DBS imposes a new activity pattern within brain circuits, favouring alpha- and gamma-like neuronal discharge, and restores the thalamo-cortical transmission pathway through axonal activation. In addition, stimulation via the dorsal contacts of the macro-electrode may affect cortical activation antidromically. However, basal ganglia (BG) modulation remains cardinal for 'OFF'-'ON' transition (as revealed by cGMP increase occurring during STN-DBS in the substantia nigra pars reticulata and internal globus pallidus). New research promises to clarify to what extent STN-DBS restores striato-centric bidirectional plasticity, and whether non-neuronal cellular actions (microglia, neurovascular) play a part. Future studies will assess whether extremely anticipated DBS or lesioning in selected patients are capable of providing neuroprotection to the synuclein-mediated alterations of synaptic efficiency. This review addresses these open issues through the specific mechanisms prevailing in a given disease stage. In patients undergoing early protocol, alteration in endogenous transmitters and recovery of plasticity are concurrent players. In advanced stages, re-modulation of endogenous band frequencies, disruption of pathological pattern and/or antidromic cortical activation are, likely, the prominent modes.

Determining the riverine carbon fluxes to oceans is critical for an improved understanding of C budgets and biogeochemical cycles (C, O) over a broad range of spatial and time scales. Among the particulate organic carbon (POC) involved in these fluxes, those yielded by sedimentary rocks (petrogenic POC: pPOC) remain somewhat uncertain as to their source on continental surfaces. Based on time series from long‐term observatories, we refine the POC and sediments flux of the Rhone River, one of the major tributaries to the Mediterranean Sea. Radiocarbon measurements on a set of riverine samples and forward modelling were used to (i) determine a modelled pPOC content and pPOC/POC ratio for each sample set, (ii) assess pPOC flux delivered to the NW Mediterranean Sea, and (iii) estimate the badlands contribution from the Durance catchment to both the pPOC and to sediment discharges. The weighted pPOC flux contributes up to 26% of the POC flux (145 Gg yr‐1) discharged into the Mediterranean Sea, whereas the weighted pPOC content reaches 0.31 wt%. Despite their low contributive surface area (0.2%), badlands provide, respectively, 12, 3.5 and 14% of the pPOC, POC and sediment fluxes to the Rhone River. Consequently, such rocks can be considered as a major source of pPOC and sediments for the NW Mediterranean Sea and potentially for oceans. We suggest that river‐dominated ocean margins, such as the Rhone River, with badlands in their catchment could export a significant amount of pPOC to the oceans.

PURPOSE To assess Italian nurses' knowledge and attitudes towards gay and lesbian sexual orientation and lesbian, gay, bisexual, and transgender (LGBT) patients, as there is currently no literature exploring the attitudes of nurses in Italy. METHODS A multicenter, cross-sectional study was conducted between May 2015 to January 2016, using a data collection tool composed of three validated questionnaires and a sociodemographic form. FINDINGS Eight hundred twenty-four nurses filled out the questionnaire. Despite their awareness of homosexuality as a "natural expression of one's sexuality," Italian nurses showed only moderately positive attitudes towards lesbian and gay patients. A more positive attitude was displayed by women when compared with men (p < .001). Greater knowledge of homosexuality was associated with female gender (p = .042), moderate-wing political affiliation (p = .014), and more affirmative behaviors (p = .008). Men were found to have greater awareness of being prepared to care for LGBT people (p = .022). CONCLUSIONS Although Italian nurses displayed moderately positive attitudes and affirmative behaviors, there is the need to increase their cultural competencies regarding sexual minorities. CLINICAL RELEVANCE LGBT patients feel some discomfort in approaching physicians or nurses. It is important to know nurses' attitudes in caring for LGBT patients in order to modify inappropriate and discriminatory behaviors.