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Stefania Paolucci,1 Federica Novazzi,1 Antonio Piralla,1 Renato Maserati,2 Roberto Gulminetti,2 Stefano Novati,2 Giorgio Barbarini,3 Paolo Sacchi,3 Alice Fratini,1 Laura Bellotti,1 Fausto Baldanti1,41Molecular Virology Unit, Microbiology and Virology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico, San Matteo, Pavia, Italy; 2Institute of Infectious Diseases, University of Pavia, Pavia, Italy; 3Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico, San Matteo, Pavia, Italy; 4Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, ItalyBackground: New hepatitis C virus (HCV) therapies have improved efficacy, allowed pangenotypic applications, increased barriers to drug resistance and shortened therapy duration.Methods: Patients infected with different HCV genotypes were divided into two groups: group 1 included 169 patients receiving genotypic specific regimens (GSR), while group 2 included 186 patients receiving pan-genotypic regimens (PGR). Patient’s HCV RNA was quantified and sequenced.Results: Comparable sustained viral response (SVR) rates were observed in both GSR and PGR treated patients. Nevertheless, even if not significant, a greater proportion of non-detectable levels (NDL) of HCV RNA was observed in patients treated with PGR as compared with GSR. Overall, among patients in the GSR and PGR groups with residual viremia, 124/169 (73.4%) and 125/186 (67.2%) at four weeks, and 66/169 (39.1%) and 58/186 (31.2%) at eight weeks, achieved SVR. No difference was observed in the clinical outcome comparing patients in the GSR and PGR groups according to genotype. While, comparing patients between the two groups, the proportion of patients with NDL HCV RNA at four and eight weeks was higher in patients infected with genotype 1b treated with PGR (p=0.0015). A significantly higher number of patients infected with 1b had RASs at baseline (p=0.0001). In addition, the proportion of patients with treatment failure was higher in patients with RASs at baseline compared with those without (p=0.012). Overall, 2.5% patients failed to achieve SVR after DAA treatment.Conclusion: A sharp HCV RNA decrease was observed in patients treated with both GSR and PGR. However, even if comparable, a slightly greater number of patients treated with PGR achieved NDL HCV RNA as compared with GSR. A significant difference was observed in patients with baseline RASs, both in relation to treatment failure and genotype. In conclusion, the use of new DAA combinations helps patients achieve a more rapid virologic response.Keywords: hepatitis C virus, drug resistance, DAA inhibitors, viral dynamics, treatment failure

James A Chiarotto,1 Riyad Akbarali,2 Lara Bellotti,2 George Dranitsaris3 1Department of Medicine, 2Department of Cardiac Rehabilitation, Scarborough and Rouge Hospital, 3Augmentium Pharma Consulting, Inc., Toronto, ON, Canada Introduction: Exercise can improve the symptoms of cancer. However, is it a cancer treatment? We tested the feasibility of group exercise for metastatic cancer patients while on chemotherapy. A biomarker for exercise efficacy in colorectal cancer (CRC), β-catenin, was tested. Methods: Patients undergoing palliative chemotherapy were eligible for a pre–post, single-arm study comprising an indefinite, weekly group exercise intervention using strength and aerobic training. The Functional Assessment of Chronic Illness Therapy (FACIT) and Piper Fatigue Scale (PFS) questionnaires were administered, and aerobic capacity assessed using the 6-minute walk test. Selection bias, as measured by invitation rate, as well as participation, compliance, and attrition rates, was measured. CRC patients had surgical sections stained for β-catenin and correlated to survival. The statistical analysis was primarily exploratory and hypothesis generating. Results: Of the 124 eligible patients, 53 (43%) patients were invited and 35 (28%) patients participated. The median number of classes attended was 16, the compliance rate was 73.1% (95% confidence interval [CI] 67.0–79.4), and the modified attrition rate was 24%. There were no injuries. No significant improvements were seen in the FACIT or PFS at 30 weeks. Aerobic capacity significantly improved at 30 weeks. Participation of CRC patients in the exercise pilot vs nonparticipation was not associated with a change in survival (hazard ratio [HR] =0.98, 95% CI 0.32–2.97). For all CRC patients, strong nuclear staining for β-catenin, compared to weak, suggested a lower risk of mortality (HR =0.54, 95% CI 0.14–1.96). However, CRC participants in the exercise program with weak nuclear staining for β-catenin had a trend to lower mortality (HR =0.39, 95% CI 0.025–6.1). Conclusion: Exercise for patients with metastatic cancer receiving chemotherapy is feasible and safe. β-Catenin is a potential biomarker for exercise anticancer effect in CRC. Keywords: strength training, aerobic training, colorectal cancer, compliance rate, attrition rate, fatigue

Purpose: To investigate the responsiveness and minimal clinically important difference (MCID) of the Functional Independence Measure (FIM) from a clinician's perspective in hip-fractured elderly undergoing inpatient rehabilitation., Materials and Methods: Data of 701 hip-fractured elderly admitted to our rehabilitation institute were retrospectively collected. Ten a priori hypotheses were formulated., Results: The effect size of the FIM scores after treatment were large (total = 1.38, motor = 1.78). Moderate correlations were found between the change total score of FIM and Barthel Index (BI, r s = 0.51), Functional Ambulation Categories (FAC, r s = 0.52) and a checklist regarding participants' independence in transfers (r s = 0.59). The area under the receiving operating characteristics were 0.82, 0.81, and 0.85 when BI, FAC and checklist were used as anchors, respectively. Based on these findings, the FIM showed high responsiveness (9/10 hypotheses met). Triangulation of findings showed that MCIDs of 22 and 21 points were the most appropriate for the FIM total and motor score, respectively., Conclusions: The FIM scale is appropriate for assessing independence and functional recovery in hip-fractured elderly. Improvements of 22 and 21 points at the total and motor FIM were identified as indicators of minimal clinical change in those admitted to a rehabilitation facility with an FIM total score between 40 and 80.

Many clinical practice recommendations indicate rehabilitation as essential for patients with sequelae of severe or critical COVID-19 and suggest the prompt initiation of a multicomponent rehabilitation program focused on aerobic and endurance training. However, randomized controlled trials (RCTs) regarding aerobic exercise are lacking. Therefore, we aimed to assess the feasibility and effectiveness of the addition of aerobic training to standard rehabilitation in subjects with subacute COVID-19. Participants were 32/214 patients with the sequelae of severe or critical COVID-19 in the acute phase who were eligible and agreed to participate in the study (eligibility = 15%, recruitment = 100%). After randomization and assessment with functional and strength tests, all the participants underwent an inpatient-tailored rehabilitation program (50 min/day, 5 days/week, 10 sessions); in addition, the experimental group performed a low- to moderate-intensity aerobic exercise (30 min/day, 10 sessions). No dropouts or severe adverse events were reported, with an attendance rate of 95.6%. Most of the secondary outcomes significantly improved in both groups, but the improvement in the Functional Independence Measure and Cumulated Ambulation Score-Italian version was significantly greater in the experimental group (at least, p < 0.05). This RCT showed that aerobic exercise is feasible and safe in subacute COVID-19. Moreover, it appears to be beneficial and useful in improving patients' independence and mobility.

The present study answers the call for more studies to investigate the age diversity climate's effect on individual-level outcomes. Building on the social identity approach and social exchange theory, we surveyed 110 Italian employees aged between 18 and 61 years old ( M = 46.10, SD = 10.02) and investigated the role of age diversity climate in predicting intentions to quit (H1), job-related wellbeing (H2), and work engagement (H3). Our findings confirmed the hypotheses (H1 and H2), showing the added effect of age diversity climate over and above age, job tenure, role clarity, job demands, job control, perceived support, and perceived job and organizational fit. In fact, age diversity climate accounted for a significant increase in the variance explained for two of the three hypothesized models (i.e., intentions to quit and job-related wellbeing, but not work engagement). To conclude, this study contributes to the existing literature by showing the age diversity climate's predictive value for turnover intentions and job-related wellbeing, and corroborating the importance of supporting age diversity through a variety of Human Resources Management strategies.

The COVID-19 pandemic significantly impacted the labor market and multiple aspects of work and workers' life. The present rapid review analyzes this impact considering the effects that COVID-19 pandemic had on employment and work-related aspects across different age groups. A comprehensive literature search was performed on scientific contributions published between 2019 and March 2021, resulting in 36 papers pertinent to the scope of this review. Findings were grouped according to different topics, all linked to age: occupational risk, implications on the labor market (i.e., job loss and reemployment, job insecurity, turnover intentions and retirement, and healthcare workers' return-to-work phase), remote work, and key individual and organizational resources and strategies. Overall, the review revealed variability across age groups in the impact this pandemic had on employment and several work-related aspects (i.e., occupational risk, remote work). Findings supported an age-differential effect of normative history-graded events such as the current pandemic, highlighting different responses and consequences depending on workers' age.

Objectives: To determine the feasibility and safety of aerobic training with an arm crank ergometer and its effectiveness in improving functional capacity and gait in patients with recent hip fracture., Design: Randomized, controlled, assessor-blinded pilot study, with intention-to-treat analysis., Setting: Inpatients, rehabilitation department., Subjects: 40 patients with hip fracture surgically treated., Interventions: Training group performed aerobic exercise with an arm crank ergometer (15 sessions, 30 minutes/day) at an intensity of 64% to 76% of maximum heart rate, in addition to conventional inpatient rehabilitation., Main Measures: Primary outcome was the feasibility (including eligibility rate, recruitment rate, number of drop-outs and adverse events, adherence). Secondary measures were the Timed Up and Go test, ability to walk independently, muscle torque of knee extensors of fractured and non-fractured leg, Functional Independence Measure., Results: Mostly due to pre-existing disability and fracture type, only 40/301 (13%) patients were eligible (age 84.6 ± 7.6 years, 75% female); all agreed to participate and 90% completed the trial, without adverse events. Adherence to aerobic exercise was good, with high attendance at sessions (93%), a strong compliance to exercise duration (95%) but lower compliance to the prescribed intensity (73%). After the program, more patients were able to walk independently in the training group ( n  = 18) compared to control ( n  = 13) ( P  < 0.05). Also the muscle torque of fractured leg knee extensors was higher in the training group ( P  < 0.05)., Conclusion: Aerobic training in addition to conventional rehabilitation after a hip fracture is feasible and safe and it was effective in improving gait performance and strength of fractured leg., Trial Registration: NCT04025866.

Background: Mother-infant bonding is of great importance for the development and the well-being of the baby. The aim of this Concurrent Cohort Study was to investigate the effects of mothers singing lullabies on bonding, newborns' behaviour and maternal stress., Methods: Eighty-three (singing cohort) and 85 (concurrent cohort) women were recruited at antenatal classes at 24 weeks g.a. and followed up to 3 months after birth. The Prenatal Attachment Inventory (PAI) and the Mother-to-Infant Bonding Scale (MIBS) were used to assess maternal-foetal attachment and postnatal bonding., Findings: No significant influence was found on Prenatal Attachment; by contrast, Postnatal Bonding was significantly greater (i.e. lower MIBS) in the singing group 3 months after birth (mean 1.28 vs 1.96; p=0.001). In the same singing group, the incidence of neonatal crying episodes in the first month was significantly lower (18.5% vs 28.2; p<0.0001) as were the infantile colic (64.7% vs 38.3%; p=0.003) and perceived maternal stress (29.6% vs 36.5%; p<0.05). Infantile colic was reduced in the singing group, even in the second month after birth (22.8% vs 36.5; p=0.002). At the same time, a reduction was observed in the neonatal nightly awakening (1.5% vs 4.7; p<0.0001)., Conclusions: Mothers singing lullabies could improve maternal-infant bonding. It could also have positive effects on neonatal behaviour and maternal stress., (Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: There is an increase in the attention to factors influencing the quality of life of cancer patients. The aim of the present study was to evaluate temperament and character traits related to health-related quality of life (HRQoL) in patients with cancer., Methods: Two hundred and three inpatients from three Italian oncology departments filled in the Temperament Character Inventory (TCI-140) based on Cloninger's personality model, the SF-36 questionnaire assessing HRQoL, and the Hospital Anxiety and Depression Scale (HADS). Eighty percent of patients were undergoing chemotherapy., Results: Lower levels of harm avoidance and higher levels of self-directedness were significantly correlated with a better HRQoL. Regression analysis controlling for psychopathology (anxiety and depression symptoms) showed that the influence of temperament and character traits on quality of life seemed to add little to the influence of psychopathology., Conclusions: The present study demonstrates the existence of some relations between HRQoL and temperament and character traits assessed using the TCI-140 questionnaire. However, among the psychological factors, psychopathology seems to retain more influence on HRQoL of cancer patients.

At the moment, PBSC collections can be performed using semi-automated or automated cell separator devices. The automated methods offer the advantages of a decreased working load for dedicated personnel and high standardization of the collection procedure. Herein we report our single institutional experience in 80 PBSC collections employing the new automated COM.TEC Fresenius autoMNC program that provides the ability to predict the total number of CD34(+) cells collected, based on the pre-leukapheresis CD34(+) cell count in peripheral blood. Fourty-eight patients and 21 healthy donors were mobilized with chemotherapy + G-CSF or G-CSF alone, respectively. Eighty leukapheresis collections were performed starting with a CD34(+) cell count in peripheral blood at least of 20/microL. Collection parameters and related side effects were evaluated. The mean CD34(+) cell collection efficiency in patients and donors was 81.8% (sd 27.6) and 95.1% (sd 15.6), respectively. The mean difference between real and predicted CD34(+) cells was +30.2% (sd 92.9) for patients and +4.6% (sd 30.3) for donors. The mean leukapheresis bag volume was 240.7 ml (sd 67.3) and 310.3 ml (sd 86.8) with a mean HCT of 10.9% (sd 34.4) and 9.2% (sd 3.9) for patients and donors, respectively. The automated PBSC collection with the new program COM.TEC Fresenius autoMNC demonstrated a very high CD34(+) cell collection efficiency. Moreover, the ability to predict the CD34(+) cell yield permits improved management of the leukapheresis collection, with the only disadvantage of larger leukapheresis volume and higher hematocrit.

Immunomagnetic CD34+ cell selection (ICS) is a widely employed technology in autotransplant and allotransplant settings. When an haploidentical transplant is performed, a high dose of purified CD34+ cells together with efficient T and B cell depletion are required to minimize the risks of graft versus host disease (GVHD) and Epstein-Barr virus (EBV)-related lymphoma. To ameliorate the performances of the CliniMACS (Miltenyi Biotec) ICS device, we compared 73 ICS performed following the manufacturer's recommended platelet depletion versus 48 performed after adjunctive centrifugations to increase platelet depletion of the leukapheresis (LKF) product. A total of 121 ICS (from single or fractioned LKF products) were carried out on 93 LKF collected from 47 related healthy donors. A statistical significance in terms of CD34+ cell recovery (81.8% vs. 71.2%) was found in favor of the modified ICS procedure (p=0.0049) with a comparable stem cell purity and viability. The modification of the standard manufacturer's technique for increasing platelet depletion can further improve the recovery of stem cells with no influence on T and B cell depletion. These results demonstrate the negative influence exerted on CD34+ cell recovery by LKF platelet contamination.

Background: The current available techniques to wash out DMSO from thawed umbilical cord blood (UCB) units are based essentially on standard centrifugation in an open system with various degrees of cell loss., Study Design and Methods: We evaluated the capacity of a new automated closed device (Cytomate, Baxter, IL) to wash out the DMSO from thawed UCB units, saving at the same time the progenitor and accessory cells in terms of CD34+ cells and MNCs. We modified the standard software of the device and calculated the cell recovery on 25 UCB units. Moreover, we set up a new gas chromatographic method to exactly detect the DMSO removal rate., Results: To evaluate the efficiency of the Cytomate device, we considered the postthawing (prewashing) versus postwashing cell recovery. The average recovery (%) in terms of total nucleated cells was 63.30 (range, 40.12-89.00), CD34+ cells was 70.20 (range, 11.51-89.01), CD3+ cells was 61.01 (range, 28.80-87.08), CD4+ cells was 62.53 (range, 30.62-96.73), CD8+ cells was 57.4 (range, 26.87-94.72), CD19+ cells was 63.33 (range, 39.10-90.33), CD16+/56+ cells was 70.67 (range, 8.91-98.40), CFU-GM was 74.33 (range, 20.23-98.60), total CFUs was 82.34 (range, 14.83-247.12), and viability was 89.67(range, 70.74-98.30). The total working time required was, on average, 15 minutes (range, 7-20)., Conclusions: The Cytomate device demonstrated a satisfying efficiency in cell recovery and in maintaining the clonogenic power of the UCB graft. The removal rate of DMSO was practically complete with evident advantages for the recipient. Finally, the entire manipulation performed in a closed system revealed to be safe, maintaining the sterility of the graft.

We analysed by immunocytochemistry the expression of p53, bcl-2 and ras proteins in bone marrow blasts from 59 patients with acute leukaemia (AL), 36 myeloid (AML) and 23 lymphoid (ALL), and from 22 patients with myelodysplastic syndrome (MDS); our aim was to examine if abnormalities in their expression were associated with peculiar biological and clinical findings, or with an altered apoptosis rate, as measured by TUNEL technique. The oncoproteins were expressed with extreme variability, without significant differences among the various morphological or immunological AL subtypes. The mean percentages of bcl-2+ blasts were significantly higher in AML than in MDS (p = 0.01), and in MDS with bone marrow blastosis than in the forms without excess of blasts (p = 0.007). The lowest percentages of apoptotic cells were observed in ALL (mean 1%, p = 0.006), whereas in MDS the apoptotic index was higher (16.7%) than in AML (8.6%) and than in the normal controls (10.8%). but the difference tended to be statistically significant only for cases of refractory anaemia. Whereas in AML and MDS the apoptotic rate was independent of the oncoprotein expression, in ALL there was a significant linear relationship between TUNEL and ras positivity (p = 0.01). Among AML patients treated with intensive polychemotherapy, no differences were observed in oncoprotein expression and apoptotic rate between responders and resistant cases. In conclusion, our data are in agreement with the hypothesis that decreased apoptosis and enhanced cell survival are associated with AL, whereas a high level of apoptosis may be responsible for the ineffective hematopoiesis in MDS; abnormal expression of oncoproteins, even if not strictly related to apoptosis level, may influence disease behaviour.